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
Claim Status
Applicant's amendment filed on March 19, 2026 has been entered.
Claims 1, 5, 7-9, 11-15, 18-20, 24-29, 31-33, 36-40, 48-61, 64, 68, 71-76, 78-95, 97-114, and 116-141. were previously canceled.
Claims 2-4, 6, 10, 16-17, 21-23, 30, 34-35, 41-47, 62-63, 65-67, 69-70, 77, 96, 115, and 142-143 are pending and under consideration.
Election/Restrictions
Applicant’s election without traverse of a single species of chimeric antigen receptor (CAR) in the reply filed on March 19, 2026 is acknowledged. Applicant has elected a CD19 CAR comprising a VH sequence of SEQ ID NO: 41, a VL sequence of SEQ ID NO: 42, a CDRL1 sequence of SEQ ID NO: 35, a CDRL2 sequence of SEQ ID NO: 36, a CDRL3 sequence of SEQ ID NO: 37, a CDRH1 sequence of SEQ ID NO: 38, a CDRH2 sequence of SEQ ID NO: 39, and a CDRH3 sequence of SEQ ID NO: 40. Further comprising the spacer set forth in SEQ ID NO: 1, the transmembrane domain set forth in SEQ ID NO: 8, the 4-1BB costimulatory signaling domain set forth in SEQ ID NO: 12, and the CD3-zeta (CD3z) signaling domain set forth in SEQ ID NO: 13.
The elected species corresponds to the CAR recited in instant claim 77.
Priority
This application is a 371 of PCT/US2022/022377 filed March 29, 2022 which claims the benefit of U.S. Provisional Application No. 63/167,596 filed March 29, 2021.
Claim Objections
Claim 45 is objected to because of the following informalities:
Claim 45 - delete the extra space between “wherein each dose”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 10, 16-17, 22-23, 34-35, 42-47, and 143 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 10, 16-17, 22-23, 34-35, 42-43, and 45-47 are drawn to “each dose” of the PD-1 inhibitor or “each dose” or “doses” of the LAG3 inhibitor. However, there is no antecedent basis for administering more than one dose of a PD-1 inhibitor or a LAG3 inhibitor in the claims, as the rejected claims depend from claim 2 which recites administering “a PD-1 inhibitor” and “a LAG3 inhibitor”, and is not suggestive of administering a plurality of doses.
For the purpose of examination, the claims are interpreted as referring to a dose of the PD-1 inhibitor or the LAG3 inhibitor broadly. For example, claim 10 is interpreted as the PD-1 inhibitor is administered at a dose between at or about 140 mg and at or about 580 mg, inclusive.
Claim 44 recites the term “with the same frequency” which is a relative term that renders the claim indefinite. The specification does not provide a definition for the term. Therefore the term “with the same frequency” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
For the purpose of examination, the claim is interpreted as the PD-1 inhibitor and the LAG3 inhibitor are always administered on the same day(s), and never administered alone during a 24 hour (1 day) period throughout the entire treatment regimen.
Claim 46 recites the term “half as frequently” which is a relative term that renders the claim indefinite. The specification does not provide a definition for the term. Therefore the term “half as frequently” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, if the PD-1 inhibitor is administered for 5, 7, or 9 doses, how can the LAG3 inhibitor be administered half as frequently?
For the purpose of examination, the claim is interpreted as the PD-1 inhibitor must be administered for an even number of days for at least two days, wherein the PD-1 inhibitor is administered at a ratio of 2:1 of the administration of the LAG3 inhibitor.
Claim 143 recites the term “fixed-dose combination” which is a relative term that renders the claim indefinite. The specification does not provide a definition for the term. Therefore the term “fixed-dose combination” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The only mention of a “fixed-dose” is in regard to Opdualag, a fixed-dose immunotherapy combination treatment of nivolumab and relatlimab in a single injection [0241]. Therefore, for the purpose of examination, the claim is interpreted as being a combination of a PD-1 inhibitor and a LAG3 inhibitor in the same vessel (i.e. syringe) for administering to a subject.
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.
Claims 2-4, 6, 10, 16-17, 21-22, 30, 34, 41-42, 44-46, 62-63, 65-67, 69-70, 77, 96, 115, and 142 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson et al. (WO 2020/113194; Cited IDS 7/16/2024) (“Albertson”) in view of Ascierto et al. (J Clin Oncol, 2017; 35(15suppl):9520; Cited IDS 7/16/2024) (“Ascierto”).
The instant claims are drawn to a method of treating a cancer comprising administering to a subject having a CD19-expressing cancer an anti-CD19 chimeric antigen receptor (CAR), a PD-1 inhibitor, and a LAG3 inhibitor, wherein the PD-1 inhibitor is nivolumab and the LAG3 inhibitor is relatlimab. The method further comprising administrating a lymphodepleting therapy prior to administering the dose of engineered T cells, wherein the dose of engineered T cells comprises between about 5 x 107 CAR-expressing T cells and about 1.1 x 108 CAR-expressing T cells, inclusive of each, and wherein the subject is relapsed or refractory to at least two prior lines of systemic therapy for the CD19-expressing cancer. The PD-1 inhibitor and LAG3 inhibitor are administered 1 to 19 days after the administration of the CD19 CAR T cells, wherein at least 2 doses of the PD-1 inhibitor of 140-580 mg are administered every two weeks (Q2W), and wherein the LAG3 inhibitor is administered at a dose of 60 to 540 mg every two weeks (Q2W), or when doses of the LAG3 inhibitor are administered half as frequently as doses of the PD-1 inhibitor.
Albertson teaches methods for treating relapsed or refractory large B cell lymphoma comprising administering a dose of T cells comprising a chimeric antigen receptor (CAR) that specifically binds to CD19, wherein the dose of T cells comprises between 1 x 107 CAR-expressing T cells and about 2 x 108 CAR-expressing T cells, inclusive [claim 1] (instant claims 2 (partial), 96, 142). Wherein the subject has relapsed following remission after treatment with, or become refractory to, two or more prior therapies for the disease or condition other than another dose of cells expressing the CAR [claim 24] (instant claim 115). Albertson further teaches that prior to administration of the engineered T cells the subject has been preconditioned with a lymphodepleting therapy comprising the administration of fludarabine and/or cyclophosphamide [claim 77] (instant claim 70).
Albertson teaches that the CAR comprises an extracellular antigen-binding domain specific for CD19, a transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3z cytoplasmic signaling domain, wherein the antigen-binding domain is an scFv comprising a variable heavy chain region of FMC63 and a variable light chain region of FMC63. The CAR further comprises a spacer between the transmembrane domain and scFv which is an IgG4 hinge spacer of 15 amino acids or less [claims 107-108, 110, 115-116, 119] (instant claim 77).
Albertson teaches the CAR comprises an scFv with the amino acid sequence of RASQDISKYLN (SEQ ID NO: 35), SRLHSGV (SEQ ID NO: 36), GNTLPYTFG (SEQ ID NO: 37), DYGVS (SEQ ID NO: 38), VIWGSETTYYNSALKS (SEQ ID NO: 39), and YAMDYWG (SEQ ID NO: 40) [claim 109]. The CAR further comprises a CD3zeta signaling domain of SEQ ID NO: 13 [claim 114], a 4-1BB costimulatory domain of SEQ ID NO: 12 [claim 112], a hinge spacer of SEQ ID NO: 1 [claim 118], and a CD28 transmembrane domain of SEQ ID NO: 8 [0672].
Albertson also teaches that administration of an immune checkpoint inhibitor, prior to, concomitantly with or at the same time and/or subsequently to initiation of administration of CAR T cells enhances, boosts, and promotes the efficacy and/or safety of the therapeutic effect of the cell therapy and/or enhances or improves the efficacy, survival or persistence of the administered CAR T cells [0900-0901]. Albertson teaches the immune checkpoint inhibitor is an antibody that totally or partially reduces, inhibits, interferes with or modulate one or more checkpoint proteins, including PD-1, PD-L1, PD-L2, or LAG-3 [0908-0909]. Exemplary immune checkpoint inhibitors include nivolumab (anti-PD-1 antibody) and BMS-986016 (anti-LAG-3 antibody) [0911-0915] (instant claims 2 (partial), 62-63, 65-67, 69). The antibodies are administered 1 to 12 days after administration of the CAR T cells [0973] (instant claims 3, 6 (partial)).
The instant specification discloses that nivolumab comprises the VH CDR amino acid sequences of SEQ ID NOs: 60, 61, and 62 and the VL CDR amino acid sequences of SEQ ID NOs: 63, 64, and 65 as recited in the instant claims [0098].
The instant specification further discloses that the anti-LAG3 antibody BMS-986016 taught by Albertson is also known as relatlimab [0240] which comprises the VH CDR amino acid sequences of SEQ ID NOs: 68, 69, and 70 and the VL CDR amino acid sequences of SEQ ID NOs: 71, 72, and 73 as recited in the instant claims [0099].
Additionally, the CD19 CAR taught by Albertson is 100% identical to the CD19 CAR elected by the Applicant in the reply received March 19, 2026, having the same amino acid sequences and sequence identifiers (SEQ ID NOs) for the FMC63 scFv, hinge, transmembrane domain, CD3z stimulatory domain, and 4-1BB costimulatory domain.
Although Albertson teaches the CD19 CAR in combination with immune checkpoint inhibitors such as nivolumab or relatlimab, it does not specifically teach a treatment regimen that comprises administration of both a PD-1 inhibitor and a LAG3 inhibitor in combination with CD19 CAR T cell therapy.
Ascierto teaches the efficacy of anti-LAG-3 antibody BMS-986016 in combination with nivolumab in patients with melanoma previously treated with anti-PD-1/PD-L1 therapy [Title]. Ascierto teaches that simultaneous blockade of LAG3 + PD-1 can synergistically restore T-cell activation and enhance antitumor immunity [Background].
Specifically, Ascierto treated melanoma patients whose disease progressed on/after prior anti–PD-1/PD-L1 therapy with BMS-986016 80 mg + nivolumab 240 mg IV Q2W [Methods] (instant claims 4, 6 (partial), 10, 16-17, 21-22, 30, 34, 41-42, 44-45). Median treatment duration was 10 weeks [Results]. The disease control rate (DCR) was 45% with benefit even observed in some patients refractory to prior anti-PD-1 therapy. Ascierto teaches that the combination therapy demonstrates encouraging efficacy for patients with melanoma [Conclusion].
It would be obvious to one skilled in the art before the effective filing date of the claimed invention to combine the teachings of Albertson and Ascierto to treat CD19-expressing cancers refractory to two or more therapies with CD19 CAR T cells in combination with nivolumab and relatlimab given that Albertson teaches CD19 CAR T cell therapy in combination with one or more immune checkpoint inhibitors enhances the efficacy and of the cell therapy by improving the survival and persistence of the administered CAR T cells and Ascierto teaches a combination therapy of two immune checkpoint inhibitors, nivolumab (PD-1) and relatlimab (LAG3) for the treatment of refractory melanoma.
One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success by the teachings of Ascierto that provides a dosing regimen for the nivolumab + relatlimab combination therapy that was used to successfully treat melanoma patients refractory to prior anti-PD-1 therapy.
The dosing regimen taught by Ascierto differs from the dosing recited in instant claim 46, wherein the LAG3 inhibitor is administered half as frequently as doses of the PD-1 inhibitor. Therefore, for example, if the PD-1 inhibitor were to be administered Q4W, the LAG3 inhibitor would be administered at Q2W. However, Ascierto only teaches nivolumab and relatlimab administered at the same frequency Q2W or Q4W.
The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See also, Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007). Therefore, the invention was prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention.
Claims 23, 35, 43, 47, and 143 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson et al. (WO 2020/113194; Cited IDS 7/16/2024) (“Albertson”) as applied to claims 2-3, 62-63, 65-67, 69-70, 77, 96, 115, and 142 above, in view of Lutzky et al. (Abstract 430, J Immunother Cancer, 2020; 8(Suppl 3):A261-A262) (“Lutzky”).
The instant claims are drawn to a method of treating a cancer comprising administering to a subject having a CD19-expressing cancer an anti-CD19 chimeric antigen receptor (CAR), a PD-1 inhibitor, and a LAG3 inhibitor, wherein the PD-1 inhibitor is nivolumab and the LAG3 inhibitor is relatlimab. The method further comprising administrating a lymphodepleting therapy prior to administering the dose of engineered T cells, wherein the dose of engineered T cells comprises between about 5 x 107 CAR-expressing T cells and about 1.1 x 108 CAR-expressing T cells, inclusive of each, and wherein the subject is relapsed or refractory to at least two prior lines of systemic therapy for the CD19-expressing cancer, wherein the PD-1 inhibitor is administered at a dose of 480 mg every four weeks (Q4W) and the LAG3 inhibitor is administered at a dose of 160 mg every four weeks (Q4W).
The teachings of Albertson are set forth above.
Albertson does not teach dosing for any immune checkpoint inhibitors or that they can be formulated in a fixed-dose composition.
Lutzky teaches methods of treating metastatic uveal melanoma with a combination of nivolumab and relatlimab (BMS-986016) [Title].
Specifically, Lutzky administered nivolumab 480mg and relatlimab 160mg every 4 weeks for up to 24 months, with objective response rate (ORR) at as a primary endpoint [Methods] (instant claims 23, 35, 43, and 47). Lutzky teaches that nivolumab and relatlimab were mixed in the same bag prior to administration [Methods] (instant claim 143).
It would be obvious to one skilled in the art before the effective filing date of the claimed invention to combine the teachings of Albertson and Lutzky to treat CD19-expressing cancers refractory to two or more therapies with CD19 CAR T cells in combination with nivolumab and relatlimab given that Albertson teaches CD19 CAR T cell therapy in combination with one or more immune checkpoint inhibitors enhances the efficacy and of the cell therapy by improving the survival and persistence of the administered CAR T cells and Lutzky teaches a combination therapy of two immune checkpoint inhibitors, nivolumab (PD-1) and relatlimab (LAG3) for the treatment of uveal melanoma.
One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success by the teachings of Lutzky that provides a dosing regimen for the nivolumab + relatlimab combination therapy that was used to successfully treat uveal melanoma patients while Albertson provides a regimen for the CD19 CAR T cell therapy. Therefore, the invention was prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention.
Prior Art
The following pertinent prior art references were found during examination but were not relied upon as any ground of rejection.
Ascierto et al., “Efficacy of BMS-986016, a monoclonal antibody that targets lymphocyte activation gene-3 (LAG-3), in combination with nivolumab in pts with melanoma who progressed during prior anti-PD-1/PD-L1 therapy (mel prior IO) in all-comer and biomarker enriched populations” (Annal Oncol, 2017; 28(Suppl5):LBA 18). Cited IDS 7/16/2024.
Lipson et al., “Initial experience administering BMS-986016, a monoclonal antibody that targets lymphocyte activation gene (LAG)-3, alone and in combination with nivolumab to patients with hematologic and solid malignancies” (J ImmunoTherap Canc, 2016; 4(Suppl 1):P232). Cited IDS 3/19/2026.
Double Patenting
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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 2-3, 10, 16-17, 34-35, 46, 62-63, 65-67, 69-70, 77, 96, 115, and 142 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185-186, 191-193, 195-200, and 202 of U.S. Application No. 18/705,171, in view of Albertson et al. (WO 2020/113194; Cited IDS 7/16/2024) (“Albertson”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the same LAG3 inhibitor (relatlimab) + PD-1 inhibitor (nivolumab) for the treatment of refractory lymphoma.
The instant claims differ from the copending claims in that they do not explicitly teach nivolumab + relatlimab in combination with CD19 CAR T cell therapy.
The teachings of Albertson are set forth above.
Specifically, Albertson teaches methods for treating relapsed or refractory large B cell lymphoma comprising administering between 1 x 107 CD19 CAR T cells and about 2 x 108 CD19 CAR T cells, wherein the subject is refractory to two or more prior therapies. Albertson further teaches that prior to administration of the engineered T cells the subject has been preconditioned with a lymphodepleting therapy. Albertson teaches the identical CD19 CAR as recited in the instant application comprising an scFv targeting CD19, a transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3z cytoplasmic signaling domain, and a hinge spacer of 15 amino acids or less.
Albertson also teaches that administration of an immune checkpoint inhibitor subsequently to initiation of administration of CAR T cells enhances and promotes the efficacy of the therapeutic effect of the cell therapy and improves the survival and persistence of the administered CAR T cells.
It would have been obvious to one of ordinary skill in the art that the nivolumab + relatlimab combination immune checkpoint inhibitor therapy disclosed in the copending application could be combined with CD19 CAR T cell therapy as evidenced by Albertson that teaches the combination of CD19 CAR T cells with one or more immune checkpoint inhibitors is effective in treating refractory CD19+ cancers. As such, the instant claimed invention is an obvious modification of the copending claims in view of Albertson.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 4, 6, 21-22, 30, 41-42, and 44-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185-186, 191-193, 195-200, and 202 of U.S. Application No. 18/705,171, in view of Albertson et al. (WO 2020/113194; Cited IDS 7/16/2024) (“Albertson”) and Ascierto et al. (J Clin Oncol, 2017; 35(15suppl):9520; Cited IDS 7/16/2024) (“Ascierto”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the same LAG3 inhibitor (relatlimab) + PD-1 inhibitor (nivolumab) for the treatment of refractory lymphoma.
The instant claims differ from the copending claims in that they do not explicitly teach nivolumab + relatlimab in combination with CD19 CAR T cell therapy and do not provide dosing frequency for the antibodies.
The teachings of Albertson and Ascierto are set forth above.
Albertson teaches CD19 CAR T cell therapy in combination with one or more immune checkpoint inhibitors including nivolumab and relatlimab, but does not provide specific dosing.
Ascierto teaches a method for treating melanoma patients whose disease progressed on/after prior anti–PD-1/PD-L1 therapy comprising administering BMS-986016 80 mg + nivolumab 240 mg IV Q2W for an average of 10 weeks.
It would have been obvious to one of ordinary skill in the art that the nivolumab + relatlimab combination immune checkpoint inhibitor therapy disclosed in the copending application could be combined with CD19 CAR T cell therapy as evidenced by Albertson that teaches the combination of CD19 CAR T cells with one or more immune checkpoint inhibitors is effective in treating refractory CD19+ cancers. One of ordinary skill in the art would be motivated to use the dosing protocols taught by Ascierto with a high expectation of success given that the treatment was successfully used to treat melanoma patients refractory to prior anti-PD-1 therapy. As such, the instant claimed invention is an obvious modification of the copending claims in view of Albertson and Ascierto.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 23, 43, 47, and 143 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185-186, 191-193, 195-200, and 202 of U.S. Application No. 18/705,171, in view of Lutzky et al. (Abstract 430, J Immunother Cancer, 2020; 8(Suppl 3):A261-A262) (“Lutzky”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the same LAG3 inhibitor (relatlimab) + PD-1 inhibitor (nivolumab) for the treatment of refractory lymphoma.
The instant claims differ from the copending claims in that they do not explicitly teach nivolumab + relatlimab in combination with CD19 CAR T cell therapy and do not provide dosing frequency for the antibodies.
The teachings of Albertson and Lutzky are set forth above.
Albertson teaches CD19 CAR T cell therapy in combination with one or more immune checkpoint inhibitors including nivolumab and relatlimab, but does not provide specific dosing.
Lutzky teaches methods for treating uveal melanoma comprising administering nivolumab 480mg and relatlimab 160mg every 4 weeks for up to 24 months. Lutzky teaches that nivolumab and relatlimab were mixed in the same bag (i.e. a fixed-dose combination).
It would have been obvious to one of ordinary skill in the art that the nivolumab + relatlimab combination immune checkpoint inhibitor therapy disclosed in the copending application could be combined with CD19 CAR T cell therapy as evidenced by Albertson that teaches the combination of CD19 CAR T cells with one or more immune checkpoint inhibitors is effective in treating refractory CD19+ cancers. One of ordinary skill in the art would be motivated to use the dosing protocols taught by Lutzky with a high expectation of success given that the treatment was successfully used to treat uveal melanoma patients. As such, the instant claimed invention is an obvious modification of the copending claims in view of Albertson and Lutzky.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
Prosecution Insights