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 .
1. Claims 1 – 9, 11 – 15, 18, 20, 21, 25, 26, 28 – 31, 34 – 38, 40, 44 – 46, 49, and 53 are pending.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1 – 9, 11 – 15, 18, 20, 21, 26, 37, 38, and 53) in the reply filed on 11/25/2025 is acknowledged.
3. Claims 25, 28 – 31, 34 – 36, 40, 44 – 46, and 49 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/25/2025.
4. Claims 1 – 9, 11 – 15, 18, 20, 21, 26, 37, 38, and 53 are under consideration.
Priority
5. This application claims priority to, U.S. Provisional Patent Application serial number 62/985,553, filed March 5, 2020.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on 12/03/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
7. The drawings filed on 09/02/2022 are acknowledged.
Specification
8. The use of the term pGEM4z, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
9. Claim 13 is objected to because of the following informalities: in line 2, “EGFRViii” should read “EGFRvIII” and “IL13Rα2” should read “IL- 13Ra2” because claim 13 depends from claim 12 and claim 12 recites the abbreviations of these antigens. Therefore, for consistency, the abbreviations used in claim 12 should be used in claim 13. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
10. Claim(s) 1 – 9, 11 – 15, 18, 20, 21, and 53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Borghaei (Borghaei H, et. al. J Clin Oncol. 2009 Sep 1;27(25):4116-23) hereinafter Borghaei which is cited on the IDS filed 12/03/2025 as evidenced by Nathan (WO2017122098-A2; Filed 01/10/2017; Published 07/20/2017), hereinafter Nathan which is cited on the IDS filed 12/03/2025 and as evidenced by Hedlund (Hedlund, Gunnar, et al. PloS one 8.10 (2013): e79082.), hereinafter Hedlund in view of Gao (Gao, Qun, et al. Journal for immunotherapy of cancer 7.1 (2019): 42), hereinafter Gao in view of Azulay (Azulay, Meir, et al. Cancer Research. Jul 2018, 78 (13 Supplement) abstract # 2712 AACR Annual Meeting 2018; Chicago, IL), hereinafter Azulay.
Regarding claim 1, Borghaei teaches a method of treating non-small cell lung cancer (NSCLC) in a subject comprising administering intravenously 26 µg/kg of ABR-217620, which is a fusion protein consisting of a staphylococcal superantigen SEA/E-120 linked to a fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4 (“superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject”) (Abstract; Figure 1; page 4116, left col. last para. and right col. para. 1; page 4117; page 4118, left col. para. 1). Borghaei teaches administration of ABR-217620 with another agent, docetaxel (page 4118, left col. para. 1). Borghaei does not teach “an effective amount of an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject” of claim 1. However, Borghaei teaches substantial expansion of TCR-Vβ6.4-expressing T cells by ABR-217620 (page 4122, left col. para. 3).
Regarding claim 2, Borghaei teaches the superantigen comprises Staphylococcal enterotoxin A variant SEA/E-120 (page 4116, right col. para. 1).
Regarding claim 3, Borghaei teaches the superantigen is SEA/E-120 (page 4116, right col. para. 1) which comprises SEQ ID NO: 3 as evidenced by Nathan (SEQ ID NO: 3 in Figure 2; page 19, 0070).
Regarding claims 4 – 6, Borghaei teaches the targeting moiety comprises a Fab moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4 (page 4116, right col. para. 1).
Regarding claim 7, Borghaei teaches ABR-217620 is also known as naptumomab estafenatox (page 4116, left col. last para.). The anti-5T4 antibody in ABR-217620 taught by Borghaei comprises a heavy chain comprising amino acid residues 1 – 458 of SEQ ID NO: 8 and a light chain comprising amino acid residues 1 – 214 of SEQ ID NO: 9 in naptumomab estafenatox as evidenced by Nathan (Figure 3; page 24, 0085).
Regarding claim 8, Borghaei teaches ABR-217620 is also known as naptumomab estafenatox (page 4116, left col. last para.). The ABR-217620 superantigen taught by Borghaei comprises a first protein chain comprising SEQ ID NO: 8 and a second protein chain SEQ ID NO: 9 in naptumomab estafenatox as evidenced by Nathan (Figure 3; page 24, 0085).
Regarding claims 9 and 11, Borghaei teaches substantial expansion of TCR-Vβ6.4 -expressing T cells (“T cell” of claim 9 and “TRBV7-9” of claim 11) by ABR-217620 (page 4122, left col. para. 3). However, Borghaei does not teach the expanded T cells comprise a CAR. TRBV7 – 9 is TCRVβ6.4 as evidenced by Hedlund (page 2, right col. para. 1).
Regarding “first cancer antigen” of claims 12 – 14, Borghaei teaches 5T4 (page 4116, right col. para. 1).
Regarding “administered separately” of claim 15, Borghaei teaches daily intravenous injections of ABR-217620 resulted in the best antitumor effects (page 4117, right col. para. 2). Borghaei teaches administration of ABR-217620 in combination with docetaxel where docetaxel is administered separately from ABR-217620 (page 4118, left col. para. 1). Borghaei does not teach administration of immune cells.
Regarding claim 53, Borghaei teaches evaluation of ABR-217620 in patients with advanced solid malignancies where the cancer is non-small-cell lung cancer (NSCLC), pancreatic cancer and renal cell cancer (Abstract; page 4117, left col. para. 1 and right col. last para.)
Borghaei does not teach “an effective an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject” of claim 1, 9, and 11 or “second cancer antigen” of claim 1, 12, and 13 or “a PD-1 based inhibitor” of claim 18, or “an anti-PD-1 antibody” of claim 20, or “pembrolizumab” of claim 21. However, Borghaei teaches ABR-217620’s proposed mechanism of action is Fab targeting of ABR-217620 to tumor with the superantigen portion of the fusion protein eliciting a potent tumoricidal cytotoxic T cell response (page 4116, left col. last para. and right col. para. 1; Figure1). Borghaei teaches ABR-217620 caused a pronounced and selective expansion of the superantigen SEA/E-120 reactive T-cell population (Figure 2C; page 4121, left col. para. 3). Borghaei teaches ABR-217620 combined with docetaxel enhanced T-cell infiltration in the tumors from two patients with NSCLC whose tumors expressed 5T4 with one patient showing massive tumor-associated infiltration of CD3-positive cells and apparent tumor cell destruction (page 4121, left col. last para.; Figure 3; page 4122, left col. para. 3). Borghaei teaches under normal circumstances, there are very few lymphocytes present in most solid tumor unless there is an inflammatory reaction at the tumor site and that the observed tumor infiltration was due to ABR-217620. Borghaei teaches ABR-217620 treatment with docetaxel resulted in stable disease and partial remission (page 4121, right col. para. 3). Borghaei teaches superantigens bind to MHC class II molecules and activate cytotoxic and helper T lymphocytes by interacting with the variable part of the T-cell receptor beta chain (page 4121, right col. para. 4). Borghaei teaches the T-cell infiltration and apparent destruction of tumor cells with dose-dependent T-lymphocyte cytokine induction and substantial expansion of TCR-Vβ6.4-expressing T cells provide evidence of the mechanism of ABR-217620 (page 4122, left col. para. 3). Borghaei teaches ABR-217620 can be safely administered to patients with advanced malignancies and evaluation of the full utility of ABR-217620 in combination with currently available therapies to enhance immunologic antitumor activity is planned (page 4122, left col. last para.).
Regarding “an effective an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject” of claim 1, 9, and 11 and “second cancer antigen” of claim 1, 12 and 13, Gao teaches a method of treating subjects with lung tumors comprising administering CAR-T cells (“immune cell” of claim 1; “T cell” of claim 9) where the CAR binds HER2 (“second cancer antigen” of claim 1, 12, 13) (page 4, left col. para. 3 – 4 and right col. para. 1; Figure 7A). Gao teaches administering the CAR-T cells alone or in combination with docetaxel (page 4, right col. para. 1; page 11, right col. para. 2 – 3; Figure 7A; page 13, left col. para. 1). Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells compared to untreated or single treated groups and attenuated tumor growth (page 11, right col. para. 2; Figure 7B – D and F).
Gao does not teach “a PD-1 based inhibitor” of claim 18, or “an anti-PD-1 antibody” of claim 20, or “pembrolizumab” of claim 21. However, Gao teaches overall survival in NSCLC patients was positively correlated with the amount of infiltrating CD8+ T cells (Figure 1E; page 5). Gao teaches the infiltration of CD8+ T cells in patients that had been treated with docetaxel was much higher (Figure 2d; page 6, left col. para. 2 and right col. para. 1). Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors , however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment (page 2, left col. para. 2; page 13, left col. para. 2). Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter (page 13, left col. para. 2). One would have been motivated to combine the teachings of Borghaei and Gao because both teach methods of treating NSCLC by increasing the number of cytotoxic T cells infiltrating the tumor using two different cancer antigens where Borghaei teaches ABR-217620 (anti-5T4) expands TRBV7-9 T cells and the combination of ABR-217620 and docetaxel resulted in enhanced T cell infiltration with partial remission and Gao teaches CAR-T cells (anti-HER2) and docetaxel had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
Regarding claims 18, 20, and 21, Azulay teaches synergistic anti-tumor effect of naptumomab estafenatox (Nap) with anti-PD-1 antibody pembrolizumab (Introduction, left col. para. 2 and last para.; Figure 3). Azuly teaches co-culturing superantigen activated T cells with NSCLC cells resulted in an increase in tumor staining for PDL-1, which was further elevated in the presence of Nap (In vitro Results, left col. para. 5 – 6; Figure 2). Azulay teaches the combination of anti-PD-1 with Nap produced the most significant reduction in tumor cell viability (In vitro Results, left col. para. 6; Figure 3). Azulay teaches the combination of a superantigen conjugate with anti-PD-1 reduced the number of lung tumors in vivo and significantly increased survival (Figure 4B and 5). Azulay teaches the combination of superantigen conjugate and anti-PD-1 results in increased T cell infiltration in lung tumors (Figure 6 – 7). Azulay teaches Nap increases tumor recognition by both coating tumor cells with bacterial-derived superantigens as well as selectively expanding T cell lineages that can recognize it which are T cells that express T cell receptor Vβ7.9 as shown in Figure 1 (Introduction, left col. para. 1 and 3). Azulay teaches after administration of Nap, Vb7.9 T lymphocytes are activated, proliferate, and differentiate into effector cells, which later localize to the tumor and mediate their antitumor functions (Introduction, left col. para. 4). Azulay teaches the combination of superantigen conjugate and anti-PD-1 monotherapy may offer clinical benefit (Conclusion, right col.).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Borghaei regarding a method of treating cancer by administering ABR-217620 and docetaxel with the teachings of Gao regarding a method of treating cancer comprising administering CAR-T cells that binds HER2 with the teachings of Azulay regarding a method of treating cancer comprising administering Nap and anti-PD1 to arrive at the claimed method comprising administering to the subject: (i) an effective amount of a superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject; and (ii) an effective amount of an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject. One would have been motivated to combine the teachings of Borghaei, Gao, and Azulay in a method of treating cancer as Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors , however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment and Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter and Azulay teaches Nap increases tumor recognition by both coating tumor cells with bacterial-derived superantigens as well as selectively expanding T cell lineages that can recognize it which are T cells that express T cell receptor Vβ7.9. One would have a reasonable expectation of success in combining the teachings as Azulay teaches after administration of Nap, Vb7.9 T lymphocytes are activated, proliferate, and differentiate into effector cells, which later localize to the tumor and mediate their antitumor functions and Borghaei teaches ABR-217620 and docetaxel treatment resulted in stable disease and partial remission and Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
11. Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Borghaei (Borghaei H, et. al. J Clin Oncol. 2009 Sep 1;27(25):4116-23) hereinafter Borghaei which is cited on the IDS filed 12/03/2025 in view of Gao (Gao, Qun, et al. Journal for immunotherapy of cancer 7.1 (2019): 42), hereinafter Gao.
Claim 26 depends from claim 25 which recites a pharmaceutical composition comprising: (i) a superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject; (ii) an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject; and (iii) a pharmaceutically acceptable carrier or diluent.
Borghaei teaches a method of treating non-small cell lung cancer (NSCLC) in a subject comprising administering intravenously 26 µg/kg of ABR-217620, which is a fusion protein consisting of a staphylococcal superantigen SEA/E-120 linked to a fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4 preceded by normal saline (“superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject” and “a pharmaceutically acceptable carrier or diluent”) (Abstract; Figure 1; page 4116, left col. last para. and right col. para. 1; page 4117; page 4118, left col. para. 1). Borghaei teaches administration of ABR-217620 with another agent, docetaxel (page 4118, left col. para. 1). Borghaei does not teach “an effective an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject”. However, Borghaei teaches substantial expansion of TCR-Vβ6.4-expressing T cells by ABR-217620 (page 4122, left col. para. 3).
Borghaei does not teach “an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject”. However, Borghaei teaches ABR-217620’s the proposed mechanism of action is Fab targeting of ABR-217620 to tumor with the superantigen portion of the fusion protein elicits a potent tumoricidal cytotoxic T proof-of-mechanism cell response (page 4116, left col. last para. and right col. para. 1; Figure1). Borghaei teaches ABR-217620 caused a pronounced and selective expansion of the superantigen SEA/E-120 reactive T-cell population (Figure 2C; page 4121, left col. para. 3). Borghaei teaches ABR-217620 combined with docetaxel enhanced T-cell infiltration in the tumors from two patients with NSCLC whose tumors expressed 5T4 with one patient showing massive tumor-associated infiltration of CD3-positive cells and apparent tumor cell destruction (page 4121, left col. last para.; Figure 3; page 4122, left col. para. 3). Borghaei teaches under normal circumstances, there are very few lymphocytes present in most solid tumor unless there is an inflammatory reaction at the tumor site and that the observed tumor infiltration was due to ABR-217620. Borghaei teaches ABR-217620 treatment with docetaxel resulted in stable disease and partial remission (page 4121, right col. para. 3). Borghaei teaches superantigens bind to MHC class II molecules and activate cytotoxic and helper T lymphocytes by interacting with the variable part of the T-cell receptor beta chain (page 4121, right col. para. 4). Borghaei teaches the T-cell infiltration and apparent destruction of tumor cells with dose-dependent T-lymphocyte cytokine induction and substantial expansion of TCR-Vβ6.4-expressing T cells provide evidence of the mechanism of ABR-217620 (page 4122, left col. para. 3). Borghaei teaches ABR-217620 can be safely administered to patients with advanced malignancies and evaluation of the full utility of ABR-217620 in combination with currently available therapies to enhance immunologic antitumor activity is planned (page 4122, left col. last para.).
Regarding “an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject”, Gao teaches a method of treating subjects with lung tumors comprising administering CAR-T cells where the CAR binds HER2 (page 4, left col. para. 3 – 4 and right col. para. 1; Figure 7A). Gao teaches administering the CAR-T cells alone or in combination with docetaxel (page 4, right col. para. 1; page 11, right col. para. 2 – 3; Figure 7A; page 13, left col. para. 1). Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells compared to untreated or single treated groups and attenuated tumor growth (page 11, right col. para. 2; Figure 7B – D and F). Gao teaches overall survival in NSCLC patients was positively correlated with the amount of infiltrating CD8+ T cells (Figure 1E; page 5). Gao teaches the infiltration of CD8+ T cells in patients that had been treated with docetaxel was much higher (Figure 2d; page 6, left col. para. 2 and right col. para. 1). Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors , however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment (page 2, left col. para. 2; page 13, left col. para. 2). Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter (page 13, left col. para. 2). One would have been motivated to combine the teachings of Borghaei and Gao because both teach methods of treating NSCLC by increasing the number of cytotoxic T cells infiltrating the tumor using two different cancer antigens where Borghaei teaches ABR-217620 (anti-5T4) expands TRBV7-9 T cells and the combination of ABR-217620 and docetaxel resulted in enhanced T cell infiltration with partial remission and Gao teaches CAR-T cells (anti-HER2) and docetaxel had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Borghaei regarding a method of treating cancer by administering ABR-217620 and docetaxel with the teachings of Gao regarding a method of treating cancer comprising administering CAR-T cells that binds HER2 to arrive at the claimed method comprising administering an effective amount of the pharmaceutical composition of claim 25. One would have been motivated to combine the teachings of Borghaei and Gao in a method of treating cancer as Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors, however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment and Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter. One would have a reasonable expectation of success in combining the teachings as Borghaei teaches ABR-217620 caused a pronounced and selective expansion of the superantigen SEA/E-120 reactive T-cell population and ABR-217620 combined with docetaxel enhanced T-cell infiltration in the tumors with one patient showing massive tumor-associated infiltration T cells and apparent tumor cell destruction and partial remission and Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
12. Claim(s) 37 and 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Borghaei (Borghaei H, et. al. J Clin Oncol. 2009 Sep 1;27(25):4116-23) hereinafter Borghaei which is cited on the IDS filed 12/03/2025 in view of Hedlund (Hedlund, Gunnar, et al. PloS one 8.10 (2013): e79082.), hereinafter Hedlund.
Claims 37 and 38 depend from claim 28 which recites a method of producing and/or expanding a T-cell for use in the treatment of a subject, the method comprising contacting T-cells with (i) a superantigen comprising Staphylococcal enterotoxin A or an immunologically reactive variant and/or fragment thereof, and (ii) a cell comprising a major histocompatibility complex (MHC) class II.
Regarding “an effective amount of a superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject” of claim 37 and “a superantigen comprising Staphylococcal enterotoxin A or an immunologically reactive variant” of claim 38, Borghaei teaches a method of treating non-small cell lung cancer (NSCLC) in a subject comprising administering intravenously 26 µg/kg of ABR-217620, which is a fusion protein consisting of a staphylococcal superantigen SEA/E-120 linked to a fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4 preceded by normal saline (Abstract; Figure 1; page 4116, left col. last para. and right col. para. 1; page 4117; page 4118, left col. para. 1). Borghaei teaches administration of ABR-217620 with another agent, docetaxel (page 4118, left col. para. 1). Borghaei does not teach “an effective amount of the T-cell of claim 35” of claims 37 and 38. However, Borghaei teaches substantial expansion of TCR-Vβ6.4-expressing T cells by ABR-217620 (page 4122, left col. para. 3).
Regarding “an effective amount of the T-cell of claim 35” of claims 37 and 38, Hedlund teaches contacting T cells with Staphylococcal enterotoxin A and MHC class II tumor cells (page 6, left col. last para.). Hedlund teaches the resulting T cells killed tumor cells (Figure 3; page 6, left col. last para.). Hedlund teaches T lymphocytes have been attributed the potential to extinguish large malignant tumors and therefore activation and regulation of these cells are corner stones in developing immune therapy of cancer (page 1, left col.). Hedlund teaches effective anti-tumor T cell responses require high numbers of selective T cells and these cells have to multiply and invade the tumor in sufficient numbers and with anti-tumor effector-function profile (page 1, left col.).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Borghaei regarding a method of treating cancer by administering ABR-217620 with the teachings of Hedlund regarding contacting T cells with Staphylococcal enterotoxin A and MHC class II tumor cells resulted in T cells that killed the tumor cells to arrive at the claimed methods comprising administering an effective amount of a superantigen conjugate comprising a superantigen covalently linked to a targeting moiety that binds a first cancer antigen expressed by cancerous cells within the subject and an effective amount of the T-cell of claim 35.. One would have been motivated to combine the teachings of Borghaei and Hedlund in a method of treating cancer as Hedlund teaches effective anti-tumor T cell responses require high numbers of selective T cells and these cells have to multiply and invade the tumor in sufficient numbers and with anti-tumor effector-function profile. One would have a reasonable expectation of success in combining the teachings as Borghaei teaches ABR-217620 caused a pronounced and selective expansion of the superantigen SEA/E-120 reactive T-cell population and ABR-217620 combined with docetaxel enhanced T-cell infiltration in the tumors with one patient showing massive tumor-associated infiltration T cells and apparent tumor cell destruction and partial remission and Hedlund teaches the T cells killed tumor cells.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
13. Claim 1 – 9, 11, 18, 20, 21, 26, 37, 38, and 53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 – 15, 17 – 19, 21, and 23 of copending Application No. 18556473 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to an overlapping subject matter of a method of treating cancer comprising administering a 5T4 targeting agent. Instant claim 1 and 26 recites “an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject” and instant claim 12 – 13 recite that the second cancer antigen may be 5T4. Instant claim 1 broadly recites “treating” and “cancer” while reference claims 1 – 3 recite “glioblastoma” and reference claim 1 recites “reducing tumor volume”, reference claim 2 recites “killing tumor cells”, and reference claim 3 recites “treating”. The instant specification defines “treating” as including “(a) inhibiting the disease, i.e., arresting its development; and (b) relieving the disease, i.e., causing regression of the disease state; and (c) curing the disease” at page 19, para. 0072 and defines “cancer” as including glioblastoma at page 14, para. 0054. Therefore, reference claims 1 – 3 are in essence a species of the generic invention of instant claim 1. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
14. Claims 1 – 9, 11, 18, 20, 21, 26, 37, 38, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 8 of U.S. Patent No. 10314910 in view of Gao (Gao, Qun, et al. Journal for immunotherapy of cancer 7.1 (2019): 42), hereinafter Gao.
Patent claim 1 recites a method of treating a cancer in a subject in need thereof , the method comprising: administering to the subject (i) an effective amount of a superantigen conjugate comprising a first protein chain comprising SEO ID NO : 8 and a second protein chain comprising SEQ ID NO : 9 that together bind a 5T4 cancer antigen expressed by cancerous cells within the subject and (ii) an effective amount of an anti-PD-1 antibody selected from nivolumab and pembrolizumab, thereby to treat the cancer, wherein the cancer is selected from non-small cell lung cancer and melanoma. Patent claim 1 lacks an effective amount of an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject of instant claim 1.
Gao teaches a method of treating subjects with non-small cell lung tumors comprising administering CAR-T cells where the CAR binds HER2 (page 4, left col. para. 3 – 4 and right col. para. 1; Figure 7A). Gao teaches administering the CAR-T cells alone or in combination with docetaxel (page 4, right col. para. 1; page 11, right col. para. 2 – 3; Figure 7A; page 13, left col. para. 1). Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells compared to untreated or single treated groups and attenuated tumor growth (page 11, right col. para. 2; Figure 7B – D and F). Gao teaches overall survival in NSCLC patients was positively correlated with the amount of infiltrating CD8+ T cells (Figure 1E; page 5). Gao teaches the infiltration of CD8+ T cells in patients that had been treated with docetaxel was much higher (Figure 2d; page 6, left col. para. 2 and right col. para. 1). Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors , however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment (page 2, left col. para. 2; page 13, left col. para. 2). Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter (page 13, left col. para. 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to modify the method of patent claim 1 to include administering CAR-T cells that binds HER2 as taught by Gao to provide dual targeting of cancer cells with 5T4 and a second cancer antigen as Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors, however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment and Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter and Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
15. Claims 1 – 9, 11, 18, 20, 21, 26, 37, 38, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 13 of U.S. Patent No. 11202829 in view of Zhang (Zhang, Chengcheng, et al. Molecular Therapy 25.5 (2017): 1248-1258.), hereinafter Zhang.
Patent claim 1 recites a method of treating a cancer in a subject in need thereof , the method comprising: administering to the subject (i) an effective amount of a superantigen conjugate comprising a first protein chain comprising SEO ID NO : 8 and a second protein chain comprising SEQ ID NO : 9 that together bind a 5T4 cancer antigen expressed by cancerous cells within the subject and (ii) an effective amount of an anti-PD-1 antibody selected from nivolumab and pembrolizumab, thereby to treat the cancer, wherein the cancer is selected from colon cancer and breast cancer. Patent claim 1 lacks an effective amount of an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject of instant claim 1.
Zhang teaches a method of administering CAR-T cells targeting carcino-embryonic antigen (CEA) to patients with colon cancer (Abstract; page 1248, right col. last para.; page 1254, right col. para. 2; page 1255, left col. para. 2). Zhang teaches the patients had a decrease in the CEA levels as response to CAR-T therapy and the serum CEA dropped to a satisfactory level providing convincing evidence of the CEA CAR-T therapy (page 1250, right col. last para.). Zhang teaches patients who experienced progressive disease in previous treatments had stable disease and one patient showed apparent attenuation of tumor activity with the CAR-T therapy and without significant toxicity (page 1251, left col. para. 1; page 1254, left col. para. 2). Zhang teaches more clinical trials with improvement of CAR-T technologies are needed to improve its safety and efficacy (page 1248, left col. para. 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to modify the method of patent claim 1 to include administering CAR-T cells targeting CEA as taught by Zhang to provide dual targeting of cancer cells with 5T4 and a second cancer antigen as Zhang teaches colon cancer patients who experienced progressive disease in previous treatments had stable disease and one patient showed apparent attenuation of tumor activity with the CAR-T therapy and without significant toxicity.
16. Claims 1 – 9, 11, 18, 20, 21, 26, 37, 38, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 13 of U.S. Patent No. 11607452 in view of Gao (Gao, Qun, et al. Journal for immunotherapy of cancer 7.1 (2019): 42), hereinafter Gao.
Patent claim 1 recites a method of treating a cancer in a subject in need thereof , the method comprising: administering to the subject (i) an effective amount of a superantigen conjugate comprising a first protein chain comprising SEO ID NO : 8 and a second protein chain comprising SEQ ID NO : 9 that together bind a 5T4 cancer antigen expressed by cancerous cells within the subject and (ii) an effective amount of an anti-PD-1 antibody selected from atezolizumab and MEDI4336, thereby to treat the cancer, wherein the cancer is selected from non-small cell lung cancer and melanoma. Patent claim 1 lacks an effective amount of an immune cell comprising an exogenous nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds a second cancer antigen expressed by cancerous cells within the subject of instant claim 1.
Gao teaches a method of treating subjects with non-small cell lung tumors comprising administering CAR-T cells where the CAR binds HER2 (page 4, left col. para. 3 – 4 and right col. para. 1; Figure 7A). Gao teaches administering the CAR-T cells alone or in combination with docetaxel (page 4, right col. para. 1; page 11, right col. para. 2 – 3; Figure 7A; page 13, left col. para. 1). Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells compared to untreated or single treated groups and attenuated tumor growth (page 11, right col. para. 2; Figure 7B – D and F). Gao teaches overall survival in NSCLC patients was positively correlated with the amount of infiltrating CD8+ T cells (Figure 1E; page 5). Gao teaches the infiltration of CD8+ T cells in patients that had been treated with docetaxel was much higher (Figure 2d; page 6, left col. para. 2 and right col. para. 1). Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors , however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment (page 2, left col. para. 2; page 13, left col. para. 2). Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter (page 13, left col. para. 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to modify the method of patent claim 1 to include administering CAR-T cells that binds HER2 as taught by Gao to provide dual targeting of cancer cells with 5T4 and a second cancer antigen as Gao teaches intense infiltration of tumor antigen-reactive T cells play a key role in eradicating tumors, however these cells often fail to inhibit the tumor because of the reduction of infiltrating effector cells in the tumor microenvironment and Gao teaches finding a way to increase the infiltration of antitumor immune cells is a pressing matter and Gao teaches tumors derived from the combination of docetaxel and CAR-T cells had the highest infiltration of HER2-CAR T cells and attenuated tumor growth.
Conclusion
No claims allowed.
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/Z.M.B./ Examiner, Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632