DETAILED ACTION
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 .
Applicant telephoned on December 16th, 2025 to request reconsideration of the after final amendment. The after final amendment, submitted December 12nd, 2025 is reconsidered and entered.
All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed December 12nd, 2025, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 12 – 14, 21, 23, and 30 – 31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022).
Regarding claims 1, 12 – 14, 21, 23, and 30 – 31, Lopez-Girona’752 teach methods for treating or preventing cancer (claim 12) comprising administering a TOR kinase inhibitor and an IMiD, that is an immunomodulatory imide drug (claim 1) (page 2 paragraph 0013). Furthermore, Lopez-Girona’752 teach embodiments wherein the methods achieve an International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response definition of complete response, partial response, or stable disease in a patient having chronic lymphocytic leukemia (claim 14) (page 2 paragraph 0014). Additionally, Lopez-Girona’752 teach embodiments wherein the methods achieve a Response Evaluation Criteria in Solid Tumors (for example, RECIST 1.1) of complete response, partial response or stable disease in a patient having a solid tumor (claim 13) (page 2 paragraph 0014).
Moreover, Lopez-Girona’752 teach that the IMiD provided herein may be capable of acting both indirectly through cytokine activation and directly on Natural Killer ("NK") cells and Natural Killer T ("NKT") cells, and increase the NK cells' ability to produce beneficial cytokines such as, but not limited to, IFN-y, and to enhance NK and NKT cell cytotoxic activity (page 19 paragraph 0142). Additionally, Lopez-Girona’752 teach that the IMiD include lenalidomide, pomalidomide, (S)-3-(4-(4-(morpholinomethyl)benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, that is the chemical name for iberdomide (claim 1) (page 183 paragraph 0580). Furthermore, Lopez-Girona’752 teach an embodiment wherein a TOR kinase inhibitor administered in combination with an IMiD can be further combined with radiation therapy or surgery (page 189 paragraph 0656). Moreover, Lopez-Girona’752 teach certain embodiments are provided herein are kits comprising a TOR kinase inhibitor and an IMiD (page 194 paragraph 0697) further comprise instructions for use, such as for administering a TOR kinase inhibitor and an IMiD (page 194 paragraph 0700).
Furthermore, Lopez-Girona’752 teach in Figure 1A that 1 µM of lenalidomide as a monotherapy, and in combination with 0.2 µM and 0.3 µM Compound 1 worked to reduce the percent of viable H929 cells (claim 30), a multiple myeloma cell line (page 3 paragraph 0018). In addition, Lopez-Girona’752 teach in Table 8 – 9 the results of incubation of Compound 1, the TOR kinase inhibitor, with lenalidomide in human cell line HepG2 and SK-HEP-1 colony formation assays (claims 21 and 23) (page 198 paragraph 0748). Moreover, Lopez-Girona’752 teach a synergistic effect of using 0.1 – 0.3 µM Compound 1 with 10 – 50 µM lenalidomide in the HepG2 (page 198 Table 8). Furthermore, Lopez-Girona’752 teach other examples of second active agents that can be tested in the cell viability assays, using for example a multiple myeloma cell line (claim 30), in combination with a TOR kinase inhibitor or, for example, one or more of dexamethasone, a corticosteroid and IMiD (pages 195 – 196 Tables 1 – 6, and page 198 paragraph 0751).
While, Lopez-Girona’752 is silent about a method for increasing ZAP-70 activity (claims 1, 21, and 31); the prior art of Lopez-Girona’752 does teach the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited in claims 1, 21, and 31, in methods for treating, the proliferative disease of cancer. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)(MPEP 2112.02(II)).
Response to Arguments
Applicant's arguments filed December 22nd, 2025 in regards to the prior art rejection of claims 1, 12 – 14, 21, 23, and 31 have been fully considered and found persuasive thus the rejection has been modified.
Applicant argues that the use of MPEP 2112.01(II) for the instant method claims was improper since the MPEP section relied upon by the examiner is regards to compound/composition claims and not method claims (see applicant’s argument page 5 paragraph 1). Moreover, applicant argues that the use of the specification by the examiner to for the argument of inherency is improper (see applicant’s argument page 5 paragraph 2).
The examiner contends that the use of MPEP 2112.01(II) was merely to highlight the fact that if the prior art taught the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited in claims 1, 21, and 31, to the same patient population that is in methods for treating, the proliferative disease of cancer then the increasing ZAP-70 activity is a property of that composition. Furthermore, outside of a showing that a particular amount, concentration, or range is critical the property, that is, an increase in ZAP-70 activity, would necessarily happen as long as the active step is completed. Thus in order to determine the effective dosage the examiner looked to the instant specification and found that in Figure 15A the effective concentration range for lenalidomide is 0.01 – 1 µM. Thus since the prior art of Lopez-Girona’752 taught administration of lenalidomide as a monotherapy at 1 µM of lenalidomide as a monotherapy in H929 cells, that is a multiple myeloma cell line, the property, that is, an increase in ZAP-70 activity, would necessarily happen.
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.
Claims 1, 12 – 14, 21, 23, and 30 – 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 8632772 B2 to Anderson et. al. (herein after Anderson’772) in view of US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022).
Anderson’772 recites a method of treating multiple myeloma (instant claims 14, and 30) in a subject, comprising administering to a subject in need thereof a first pharmaceutical composition comprising a therapeutically effective amount of HuLuc63, said HuLuc63 being a humanized IgG 1 antibody comprising the heavy chain variable region of SEQ ID NO:5 and the light chain variable region of SEQ ID NO:6, a second pharmaceutical composition comprising a therapeutically effective amount of lenalidomide (instant claim 1), and a therapeutically effective amount of dexamethasone (reference claim 1).
However, Anderson’772 fails to recite a method for increasing the activity of zeta-chain associated protein kinase-70 (instant claims 1, 21, and 31).
Nevertheless, the teachings of Lopez-Girona’752, as they relate to the prior art rejection of claims 1, 12 – 14, 21, 23, and 30 – 31, are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the invention of Anderson’772, that is for a method of treating multiple myelomas using lenalidomide in view of Lopez-Girona’752, that is for a method of increasing the activity of ZAP-70. One or ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because 1 µM of lenalidomide as a monotherapy worked to reduce the percent of viable H929 cells a multiple myeloma cell line. Thus it would have been inherent that the H929 cells a multiple myeloma cell lines treated with 1 µM of lenalidomide would have also exhibited increasing the activity of zeta-chain-associated protein kinase-70 in biological sample or cell since the cells were treated with the same concentration, that is effective dose, with the same compound. Additionally, the prior art of Lopez-Girona’752 does teach the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited instant claims 1, 21, and 31, in methods for treating, the proliferative disease of cancer. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)(MPEP 2112.02(II)).
Claims 1, 12 – 14, 21, 23, and 30 – 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 28 – 31, 33 – 35, 38 – 39, and 44 of US Patent Number US 12115151 B2 to Cheng et. al. (herein after Cheng’122) in view of US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022).
Cheng’122 recite a method of treating a p53 wild type (WT) tumor in a subject, comprising administering to the subject (a) an MDM2 inhibitor which is HDM201 (reference claims 29, 31, and 33) or nutlin-3 (reference 30) and (b) i) a CKla degrading agent which is lenalidomide (reference claim 31 and 33; instant claims 1, 21, and 31) and/or ii) an MDM4 inhibitor which is SC-24-UR-99 (reference claim 28). Furthermore, Cheng’122 recite a method wherein the p53 WT tumor is a solid tumor (reference claim 34 – 35; instant claim and 13) or wherein the p53 WT tumor is a hematological tumor or a hematologic malignancy (reference claim 38 – 39; instant claim 14). Moreover, Cheng’122 recite a method further comprising one or more further anti-cancer agent(s) (reference claim 44).
However, Cheng’122 fails to recite a method for increasing the activity of zeta-chain associated protein kinase-70 (instant claims 1, 21, and 31).
Nevertheless, the teachings of Lopez-Girona’752, as they relate to the prior art rejection of claims 1, 12 – 14, 21, 23, and 30 – 31, are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the invention of Cheng’122, that is for method of treating a p53 wild type (WT) tumor using lenalidomide in view of Lopez-Girona’752, that is for a method of increasing the activity of ZAP-70. One or ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because 1 µM of lenalidomide as a monotherapy worked to reduce the percent of viable H929 cells a multiple myeloma cell line. Thus it would have been inherent that the H929 cells a multiple myeloma cell lines treated with 1 µM of lenalidomide would have also exhibited increasing the activity of zeta-chain-associated protein kinase-70 in biological sample or cell since the cells were treated with the same concentration, that is effective dose, with the same compound.
Additionally, the prior art of Lopez-Girona’752 does teach the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited instant claims 1, 21, and 31, in methods for treating, the proliferative disease of cancer. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)(MPEP 2112.02(II)).
Claims 1, 12 – 14, 21, 23, and 30 – 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, and 25 – 26 of copending Application No. 17/634465 to Wu et.al. (herein after Wu’465) in view of US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022).
Wu’465 recite a method of treating a subject with Richter's transformation, comprising: obtaining a test sample from a subject having or at risk of having Richter's transformation (RT); determining the expression level of at least one RT-associated gene in the test sample; comparing the expression level of the RT-associated gene in the test sample with the expression level of the RT-associated gene in a reference sample; and determining whether programmed cell death protein-1 (PD-1) inhibition will inhibit RT and provide a clinical benefit to the subject if the expression level of the RT-associated gene in the test sample is differentially expressed as compared to the level of the RT-associated gene in the reference sample; and administering a PD-1 inhibitor to the subject in whom the expression level of the RT- associated gene in the test sample is differentially expressed as compared to the level of the RT-associated gene in the reference sample (reference claim 1).
Wu’465 further recites the method further comprising treating the subject with a chemotherapeutic agent, radiation therapy, cryotherapy, hormone therapy, or immunotherapy (reference claim 6; wherein the chemotherapeutic agent comprises thalidomide (instant claim 1), lenalidomide (instant claims 1, 21, and 31), ibrutinib, ixazomib, bortezomib, carfilzomib, melphalan, vincristine, cyclophosphamide, doxorubicin, liposomal doxorubicin, or bendamustine (reference claim 18).
However, Wu’465 fails to recite a method for increasing the activity of zeta-chain associated protein kinase-70 (instant claims 1, 21, and 31).
Nevertheless, the teachings of Lopez-Girona’752, as they relate to the prior art rejection of claims 1, 12 – 14, 21, 23, and 30 – 31, are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the copending Wu’465, that is for a method of treating a subject with Richter's transformation using lenalidomide in view of Lopez-Girona’752, that is for a method of increasing the activity of ZAP-70. One or ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because 1 µM of lenalidomide as a monotherapy worked to reduce the percent of viable H929 cells a multiple myeloma cell line. Thus it would have been inherent that the H929 cells a multiple myeloma cell lines treated with 1 µM of lenalidomide would have also exhibited increasing the activity of zeta-chain-associated protein kinase-70 in biological sample or cell since the cells were treated with the same concentration, that is effective dose, with the same compound.
Additionally, the prior art of Lopez-Girona’752 does teach the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited instant claims 1, 21, and 31, in methods for treating, the proliferative disease of cancer. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)(MPEP 2112.02(II)).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 12 – 14, 21, 23, and 30 – 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, and 25 – 26 of copending Application No. 19/071232 to Quayle et.al. (herein after Quayle’232) in view of US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022).
Quayle’232 recite a method for treating multiple myeloma (instant claims 1, 12, and 14) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical combination comprising a histone deacetylase 6 (HDAC6) specific inhibitor or a pharmaceutically acceptable salt thereof, and an immunomodulatory drug (IMiD) (instant claim 1, 21, and 31) or a pharmaceutically acceptable salt thereof, wherein the HDAC6 inhibitor is a compound of Formula II (reference claim 19); wherein the combination further comprises an anti- inflammatory agent (reference claim 25) wherein the anti-inflammatory agent is dexamethasone (reference claim 26).
However, Quayle’232 fails to recite a method for increasing the activity of zeta-chain associated protein kinase-70 (instant claims 1, 21, and 31).
Nevertheless, the teachings of Lopez-Girona’752, as they relate to the prior art rejection of claims 1, 12 – 14, 21, 23, and 30 – 31, are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the copending Quayle’232, that is for a method for treating multiple myeloma using lenalidomide in view of Lopez-Girona’752, that is for a method of increasing the activity of ZAP-70. One or ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because 1 µM of lenalidomide as a monotherapy worked to reduce the percent of viable H929 cells a multiple myeloma cell line. Thus it would have been inherent that the H929 cells a multiple myeloma cell lines treated with 1 µM of lenalidomide would have also exhibited increasing the activity of zeta-chain-associated protein kinase-70 in biological sample or cell since the cells were treated with the same concentration, that is effective dose, with the same compound.
Additionally, the prior art of Lopez-Girona’752 does teach the active step of the administration of the IMiDs lenalidomide, pomalidomide, as recited instant claims 1, 21, and 31, in methods for treating, the proliferative disease of cancer. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)(MPEP 2112.02(II)).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed December 12nd, 2025, with respect to the NSDP rejections of claims 1, 12 – 14, 21, 23, and 30 – 31 over claim 1 of U.S. Patent No. 8632772 B2 to Anderson et. al. (herein after Anderson’772); claims 28 – 31, 33 – 35, 38 – 39, and 44 of US Patent Number US 12115151 B2 to Cheng et. al. (herein after Cheng’122); claims 19, and 25 – 26 of copending Application No. 17/634465 to Wu et.al. (herein after Wu’465); and claims 19, and 25 – 26 of copending Application No. 19/071232 to Quayle et.al. (herein after Quayle’232) have been fully considered but they are not persuasive.
Applicant respectfully traverse the rejection in view of the lack of indication of allowable subject matter (see applicant’s remarks pages 6 – 7). Moreover, applicant argues the non-obvious NSDP rejects using similar logic as expressed in the prior art rejection above against US Patent Application Publication No. US 2014/0314752 A1 to Lopez-Girona et. al. (herein after Lopez-Girona’752; cited on the IDS dated 07/01/2022)(see applicant’s argument page 5 paragraphs 1 – 2).
The examiner reminds the applicant that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. (MPEP 804). Moreover, the examiner rebuttal in regards the NSDP rejection in view of Lopez-Girona’752 has been addressed above in the prior art response to arguments.
Conclusion
Claims 1, 12 – 14, 21, 23, and 30 – 31 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached on 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627