Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
The Amendments and Remarks filed 5/13/26 in response to the Office Action of 2/13/26 are acknowledged and have been entered.
Claims 91-97 have been added by Applicant.
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are pending.
Claims 1, 19, 45, 56, 61, 71, 72, and 88 have been amended by Applicant.
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
All previous rejections are withdrawn.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 103
Claims 1, 2, 13, 14, 19, 43, 45, 56, 71, 72, 88, and 91-97 are rejected under 35 U.S.C. 103(a) as being unpatentable over Coughlin (US 2021/0060070 A1; 3/4/21) in view of Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979) and Wardell et al (US 2018/0207201 A1; 7/26/2018).
Coughlin teaches a method for treatment of tumors comprising administering engineered cells, such as CART-TnMUC1 expressing immune cells ([0221]-[0223], in particular), wherein the CART-TnMUC1 targets the tumor antigen MUC1 ([0024 and [0072], in particular) and that CARs of such a CART target tumor associated antigens (MUC1) on (same as “surface of”) tumor cells ([0068], in particular). Coughlin further teaches a source of immune cells expressing the CART-TnMUC1 of the method include tumor infiltrating lymphocytes (TILs) ([0191], in particular). Coughlin further teaches said method wherein subject is administered CART-TnMUC1 expressing immune cells are subjects with NSCLC ([0341] and [0380], in particular). At [0345], Coughlin further teaches said method wherein a suitable subject for the method has received prior therapy for NSCLC, “including both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy or be intolerant for these standard therapies.” Coughlin further teaches said method wherein a suitable subject has had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular). Coughlin further teaches said method wherein the subject has persistent or relapsed disease following treatment with another therapeutic intervention, such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular).
Coughlin does not specifically demonstrate the method of Coughlin wherein the administered CART-TnMUC1 expressing immune cells are tumor infiltrating lymphocytes (TILs), that previous administration of a chemotherapeutic and checkpoint inhibitor was “systemic” administration, or that such TILs are processes as recited by instant claim 2. However, these deficiencies are made up in the teachings of Rizvi et al and Wardell et al.
Rizvi et al teaches therapeutically treating NSCLC patients (including adenocarcinoma and squamous cell NSCLC patients) by systemically administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based doublet chemotherapy (Abstract and page 2970, in particular). Rizvi et al further teaches 48% of the NSCLC patients have less than 1% tumor PD-L1 expression (right column on page 2974 and Table S12, in particular). Rizvi et al further teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC; however, progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular).
Wardell et al teaches an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs comprising performing a method comprising obtaining a first population of TILs from a tumor resected from a patient by processing a tumor sample from the patient into multiple tumor fragments, adding the first population of TILs to a closed container/system, performing a first expansion (same as “priming first expansion”) by culturing the first population of in a cell culture medium comprising IL-2 (including 6000 IU/mL IL-2 – see [0332] and [0334]) for 3-14 days and providing a first gas-permeable surface area to produce a second population of TILs in the closed container/system wherein the second population is at least 50-fold greater in number than the first population of TILs, performing a second expansion (same as “rapid expansion”) by supplementing the cell culture medium of the second population of TILs with additional IL-2, OKT-3 (20 ng/ml – see [0354]) and optionally IL-15 and/or IL-21 (see [0023]), and APCs, for about 7-14 days and providing a second gas-permeable surface area to produce a therapeutic third population of TILs in the closed container/system, harvesting the therapeutic third population of TILs without opening the system/container, transferring the harvested TILs to an infusion bag in the closed container/system ([0005]-[0012], in particular). Wardell et al further teaches said method wherein the infusion bag is cryopreserved ([0013], in particular). Wardell et al further teaches said method wherein the steps from obtaining to cryopreserving is performing 10 to 22 days ([0031]-[0032], in particular). Wardell et al further teaches said method wherein the patient has cancer and the patient is treated by administering a therapeutically effective dosage of the therapeutic third population of TILs from the infusion bag to the patient ([0062], in particular). Wardell et al further teaches said method wherein the cancer is NSCLC ([0076], in particular). Wardell et al further teaches said method wherein the TILs comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the method of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC with MUC1-expressin NSCLC cells that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy, and the subjects with NSCLC are adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular), Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin, and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
Further, one ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular).
Further, one ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al is taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005], in particular), is taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076], in particular), and TILs expected by method of Wardell include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629], in particular).
Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 13, 14, 19, 41, 43, 45, 56, 71, 72, 88, and 91-97 is/are rejected under 35 U.S.C. 103 as being unpatentable over Coughlin (US 2021/0060070 A1; 3/4/21) in view of Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979) and Wardell et al (US 2018/0207201 A1; 7/26/2018) as applied to claims 1, 2, 13, 14, 19, 43, 45, 56, 71, 72, 88, and 91-97 above, and further in view of Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054).
Teachings of Coughlin, Rizvi et al, and Wardell et al are discussed above.
Coughlin, Rizvi et al, and Wardell et al do not specifically comment on subjects with NSCLC as having “bulky disease” at baseline. However, these deficiencies are made up in the teachings of Samejima et al.
Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Coughlin, Rizvi et al, and Wardell et al wherein the subjects with NSCLC are any subjects with NSCLC with MUC1-expressin NSCLC cells previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 13, 14, 19, 43, 45, 56, 61, 71, 72, 88, and 91-97, is/are rejected under 35 U.S.C. 103 as being unpatentable over Coughlin (US 2021/0060070 A1; 3/4/21) in view of Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979) and Wardell et al (US 2018/0207201 A1; 7/26/2018) as applied to claims 1, 2, 13, 14, 19, 43, 45, 56, 71, 72, 88, and 91-97, and further in view of Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
Teachings of Coughlin, Rizvi et al, and Wardell et al are discussed above.
Coughlin, Rizvi et al, and Wardell et al do not specifically teach subjects treated by the combined method include subjects with NSCLC resistant or refractory to bevacizumab. However, these deficiencies are made up in the teachings of Zhang et al.
Zhang et al teaches chemotherapy as “the main treatment modality” for NSCLC patients and that chemotherapy with a platinum-based doublet is the standard of care for patients with advanced NSCLC (page 1417, in particular). Zhang et al further teaches NSCLC patients can be refractory to chemotherapy (left column on page 1421, in particular). Zhang et al further teaches the VEGF-A inhibitor bevacizumab has been approved for advanced NSCLC, but clinical benefits are modest and all patients eventually develop resistance (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Coughlin, Rizvi et al, and Wardell et al wherein the NSCLC subjects treated by the combined method include those NSCLC with MUC1-expressin NSCLC cells that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Double Patenting
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 18 of U.S. Patent No. 10166257 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 18-22 of U.S. Patent No. 10272113 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 18, 20, and 21 of U.S. Patent No. 10463697 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 18-22 of U.S. Patent No. 10646517 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21, 25, and 27-29 of U.S. Patent No. 11007225 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11939596 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 18, and 20-24 of U.S. Patent No. 11013770 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11083752 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 18-20 of U.S. Patent No. 11202804 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 18-20 of U.S. Patent No. 11241456 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 17-19 of U.S. Patent No. 11273181 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11529372 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21, 23, and 24 of U.S. Patent No. 11541077 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 and 19-23 of U.S. Patent No. 11998568 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 12121541 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11266694 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11311578 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11344581 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11351199 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11364266 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11369637 B2 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent 12570959 in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the patent claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the patent claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 1,2, 8, 9, 12-14, 16, 24, 32, 34, 36-38, 41-45, and 52 of Application No. 16/969362 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The patent claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the patent claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the patent claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the allowed claims and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the allowed claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the patent claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular).
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-16 and 19-30 of copending Application No. 18/886988 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. While copending claims are directed to species of some instant claims, some instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-16 and 19-30 of copending Application No. 18/661510 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite the steps of expanding TILs are performed in a “closed” system/container and the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7, 13, 14, 19, 20, 27-29, 30, 38, 46, 48, 50, 57, 84, 94, 106, and 112 of copending Application No. 18/858710 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/707719 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 9, 13, 15, 16, 46, 59, 69, 112-116, 119, 120, and 141 of copending Application No. 18/291536 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 162-168 of copending Application No. 18/256421 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 13, 15, 16, 18-21, 23, 34-45, 56, and 61 of copending Application No. 18/247877 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because pending claims are directed to species of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-15, 17, and 19-22 of copending Application No. 17/829087 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 65, 68-76, and 82-98 of copending Application No. 17/050552 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 2, 13, 14, 19, 41, 43, 45, 56, 61, 71, 72, 88, and 91-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 19/011427 (reference application) in view of Coughlin (US 2021/0060070 A1; 3/4/21), Rizvi et al (Journal of Clinical Oncology, 2016, 34(25): 2969-2979), Wardell et al (US 2018/0207201 A1; 7/26/2018), Samejima et al (Japanese Journal of Clinical Oncology, 2015, 45(11): 1050-1054), and Zhang et al (Expert Opinion on Investigational Drugs, 2012, 21(9): 1417-1426).
The copending claims and the instant claims are both drawn to methods of expanding tumor infiltrating lymphocytes (TILs) from an NSCLC patient and administering a therapeutically effective dose of the expanded TILs to the NSCLC patient. The instant claims differ from the copending claims in that the instant claims recite various characteristics of the NSCLC patient not recited by the copending claims.
However, it would have been obvious to perform a combined method comprising the therapeutic method of treating subjects with NSCLC of Coughlin wherein CART-TnMUC1 expressing immune cells are administered to subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy (that has been systemically administered and wherein the platinum-based chemotherapy is a platinum-based doublet chemotherapy), such as adenocarcinoma or squamous cell NSCLC patients (about half of which would predictably have tumors with less than 1% tumor cells expressing PD-L1 based on teachings of Rizvi et al) and including those that have been administered bevacizumab (left column on 2940 of Rizvi et al), wherein CART-TnMUC1 expressing immune cells are TILs because the CART-TnMUC1 expressing immune cells are taught to therapeutically target MUC1 expressing NSCLC cells, Rizvi et al teaches therapeutically treating NSCLC patients (including those with NSCLC that is adenocarcinoma or squamous cell carcinoma) by “systemically” administering a checkpoint inhibitor (anti-PD-1 nivolumab) and the platinum-based “doublet” chemotherapy (Abstract and page 2970, in particular) and Coughlin teaches treating subjects with NSCLC that have previously been treated with both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy and both Coughlin and Wardell et al teach TILs as immune cells to be used in chimeric antigen receptor immune cell therapies (see [0191] of Coughlin and [0629] of Wardell et al, in particular). Further, it would have been obvious to perform said combined method wherein the subjects include those that have (in addition to having previous therapies of checkpoint inhibition by checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 inhibitors, and platinum-based chemotherapy) also had prior therapies such as targeted therapy directed at EGFR and/or ALK alterations/mutations (whose presence has previously been found as a target on subjects of the combined method) and/or radiation and has since persistent or relapsed disease following such therapies (same as being subject having NSCLC “not indicated” for treatments that and/or resistant and/or refractory to such therapies- including EGFR and/or ALK inhibitors) because Coughlin teaches administering such CART-TnMUC1 expressing immune cells wherein subject have had prior targeted therapy directed at EGFR or ALK alterations/mutations in addition to checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy ([0345], in particular) and wherein subjects have persistent or relapsed disease following treatment with another therapeutic intervention (indicative of “refractory” or “resistant” to the treatment), such as radiation, chemotherapy and, in some embodiments, the administration of the immune cells effectively treats the subject despite the subject having become resistant to another therapy ([0237], in particular). Further, it would have been obvious to perform said combined method wherein, prior to administration of the TILs expressing CART-TnMUC1, the TILs are expanded by the method of the copending and Wardell et al into a therapeutic population of TILs expressing CART-TnMUC1 (a chimeric antigen receptor which bind to a tumor-associated cell surface molecule) because the method of Wardell et al and the copending claims are taught to be an “improved and/or shortened” method of expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs ([0005] of Wardell, in particular), are taught to provide therapeutic benefit to patients with NSCLC ([0062] and [0076] of Wardell, in particular), and TILs expanded by the method of Wardell and the copending claims include those that comprise a chimeric antigen receptor which bind to a tumor-associated cell surface molecule ([0629] of Wardell, in particular). Further, said combined method would result in a partial response or complete response per RECIST v1.1 (as recited by instant claim 1) because the combined method provides therapeutic benefit and administers reagents encompassed by the instant claims to patients recited by instant claims and responses of NSCLC patients to therapies are determined by RECIST v1.1 (Abstract of Rizvi et al, in particular).Further, it would be obvious to perform the combined method wherein the subjects with NSCLC are any subjects with NSCLC previously administered both checkpoint inhibition (PD-1/PD-L1 directed therapy) and platinum-based chemotherapy wherein the NSCLC tumors express MUC1 because the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells. Such NSCLC patients include those NSCLC patients with “bulky” disease at any time point because Samejima et al teaches NSCLC patients can have “bulky” or “non-bulky” disease, wherein bulky disease is determined as swollen lymph nodes with short-axis diameter ≥20 mm (Abstract, in particular). Further, it would be obvious to perform the combined method wherein the NSCLC subjects treated by the combined method include those NSCLC that have been treated VEGF-A inhibitor bevacizumab and/or platinum-based doublet of Zhang et al (and Rizvi et al) that have become refractory or resistant to chemotherapy and/or bevacizumab because NSCLC patients predictably benefit from the combined method due to the CART-TnMUC1 expressing immune cells of the combined method target MUC1-expressin NSCLC cells, Rizvi et al teaches bevacizumab (VEGF-A inhibitor) and maintenance chemotherapies have shown to provide therapeutic benefit to subjects with NSCLC but that progression and resistance to chemotherapeutic agents invariably develops (left column on page 2970, in particular), and Zhang et al teaches all patients with NSCLC administered the FDA approved bevacizumab for treating advanced NSCLC eventually develop resistance (Abstract, in particular). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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