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 .
Status of the Claims
Claims 1 – 20 were pending. Claims 1, 3 – 6, 10 – 11 and 15 have been amended; claims 2 and 7 have been canceled; and claim 21 has been newly added. Claims 1, 3 – 6 and 8 – 21 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 06/01/2026 and 06/16/2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered.
REJECTIONS WITHDRAWN
Claim Rejections - 35 USC § 112
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In view of the claim amendments in the reply of 06/01/2026, this rejection is withdrawn.
Double Patenting
Claims 1 – 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of U.S. Patent No. 11,685,777 in view of ADAMS (US 2019/0352421 A1; published 11/21/2019; see PTO-892: Notice of References Cited of 12/01/2025) and FERTIG (WO 2019/154890 A1, see PTO-892 of 12/01/2025).
In view of the claim amendments in the reply of 06/01/2026, this rejection is withdrawn.
Claims 1 – 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 28 of U.S. Patent No. 12,065,500 in view of ADAMS and FERTIG.
In view of the claim amendments in the reply of 06/01/2026, this rejection is withdrawn.
Claims 1 – 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 – 9, 11 – 18, and 24 – 32 of copending Application No. 17/477,435 in view of ADAMS and FERTIG.
In view of the claim amendments in the reply of 06/01/2026, this rejection is withdrawn.
Claims 1 – 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 213 – 256 of copending Application No. 18/208,361 in view of ADAMS and FERTIG.
In view of the claim amendments in the reply of 06/01/2026 and the later filing date of the copending application, this rejection is withdrawn.
NEW REJECTION, NECESSITATED BY CLAIM AMENDMENTS
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites “further comprising subcutaneously administering to the subject 10 µg/kg of the GPRC5DxCD3 bispecific antibody and 60 µg/kg of the GPRC5DxCD3 bispecific antibody, prior to the initial subcutaneous administration of the GPRC5DxCD3 bispecific antibody”. However, the comma after “antibody” of line 2 separates the phrase “prior to the initial subcutaneous administration of the GPRC5DxCD3 bispecific antibody” from the rest of the claim. Thus, the phrase “prior to the initial subcutaneous administration of the GPRC5DxCD3 bispecific antibody” seems to refer to “further comprising subcutaneously administering to the subject 10 µg/kg of the GPRC5DxCD3 bispecific antibody and 60 µg/kg of the GPRC5DxCD3 bispecific antibody”. The meaning of the phrase “further comprising subcutaneously administering to the subject 10 µg/kg of the GPRC5DxCD3 bispecific antibody and 60 µg/kg of the GPRC5DxCD3 bispecific antibody” is not clear.
REJECTIONS MAINTAINED IN MODIFIED FORM
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 1, 3 – 6, 8 – 10, 12 – 14 and 17 - 21 are rejected under 35 U.S.C. 103 as being unpatentable over ADAMS (US 2019/0352421 A1; published 11/21/2019; see PTO-892: Notice of References Cited of 12/01/2025) in view of FERTIG (WO 2019/154890 A1, see PTO-892 of 12/01/2025).
Present independent claim 1 is directed to a method of treating relapsed or refractory multiple myeloma in a subject in need thereof, comprising: (1) administering to the subject a GPRC5DxCD3 bispecific antibody at a dose of 400µg/kg weekly or 800 µg/kg biweekly; and (2) administering to the subject an anti-CD38 antibody at a dose of 1800 mg once every week during week 1 to week 8 of the treatment, once every two weeks during week 9 to week 24 of the treatment, and once every four weeks after week 24 of the treatment.
ADAMS is directed to a method of treating relapsed or a refractory multiple myeloma (MM) (see ADAMS at claim 32) in a subject, comprising administering a therapeutically effective amount of an anti-CD38 antibody and a GPRC5DxCD3 bispecific antibody (see ADAMS at claims 1 and 49) where the anti-CD38 antibody is administered at about 1,800 mg (see ADAMS at claims 55 and 90) and that the anti-CD38 antibody may be administered at weekly intervals for 8 weeks, followed by administration at every two weeks for an additional 16 weeks, followed by administration at every four weeks by intravenous infusion (see ADAMS at paragraph 0368).
However ADAMS does not expressly teach the administration of a GPRC5DxCD3 bispecific antibody at a dose of 400µg/kg weekly or 800 µg/kg biweekly.
FERTIG is directed to antibodies that bind to GPRC5D, including bispecific antigen binding molecules e.g. for activating T cells. See abstract. FERTIG teaches a bispecific antigen binding molecule, comprising (a) a first antigen binding moiety that binds to GPRC5D and (b) a second antigen binding moiety which specifically binds to CD3 (see FERTIG at claims 8 and 10).
Furthermore, FERTIG teaches that efforts have been made towards selectively depleting the plasma cells in multiple myeloma and that so far, there are few cases of successful biologics as e.g. represented by daratumumab (anti-CD38). See FERTIG at p. 1, lines 18 – 22. Thus, FERTIG, along with the teaching of a GPRC5DxCD3 bispecific antibody, also teaches that the anti-CD38 antibody daratumumab has been successful in the treatment of MM.
FERTIG teaches that one or more doses of the bispecific antibody of about 0.5 mg/kg, 2.0 mg/kg, 5.0 mg/kg or 10 mg/kg (or any combination thereof) may be administered to the patient. Such doses may be administered intermittently, e.g. every week or every three weeks (e.g. such that the patient receives from about two to about twenty, or e.g. about six doses of the antibody or bispecific antigen binding molecule). See FERTIG at p. 136, lines 8 – 10. Although, FERTIG does not expressly teach the recited dose of 400µg/kg weekly or 800 µg/kg biweekly of present claim 1, FERTIG also teaches about 1μg/kg to 15 mg/kg (e.g. 0.1 mg/kg - 10 mg/kg) of antibody or bispecific antigen binding molecule can be an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations (see FERTIG at p. 135, lines 20 – 23). Thus, the claimed GPRC5DxCD3 bispecific antibody doses of 400µg/kg weekly or 800 µg/kg biweekly can be arrived at with routine experimentation. “[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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. See MPEP 2144.05 (I) and (II).
Overall, because ADAMS teaches a GPRC5DxCD3 bispecific antibody (which FERTIG teaches may be administered in doses and regimens that overlap those recited in the present claims) that is combined with an anti-CD38 antibody at the doses and regimens recited in the present claims to treat relapsed or refractory MM and administered subcutaneously (see ADAMS at paragraph 0474), it would have been obvious to combine the methods of ADAMS and FERTIG to arrive to the inventions of present claims 1, 5 – 6, 14, and 21. There would have been a reasonable expectation of success considering that administering the GPRC5DxCD3 bispecific antibody alone or in combination with an anti-CD38 antibody is known to successfully treat cancer as evidenced by the applied prior art.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of ADAMS and FERTIG. The artisan would have been motivated to use the method of claim 1 because ADAMS teaches methods that enhance T cell functionality for optimal efficacy of the therapeutics mediating T cell redirected killing (see ADAMS at paragraph 0005) and FERTIG teaches T-cell bispecific antibodies targeting GPRC5D that have the potency to treat multiple myeloma (see FERTIG at p. 2, lines 21 – 23). Thus, the artisan would have a reasonable expectation of success with the combined teachings of ADAMS and FERTIG.
Regarding claims 3 – 4, ADAMS teaches that the T-cell redirecting therapeutic that binds GPRC5D and the anti-CD38 antibody is administered by a subcutaneous injection (see paragraph 0474). FERTIG teaches that the disclosed bispecific antibody may be administered at a dose of about 10 microgram/kg body weight, about 50 microgram/kg body weight, about 100 microgram/kg body weight, and that an initial higher loading dose, followed by one or more lower doses may be administered. See FERTIG at p. 135, lines 28 – 30 and p. 136, lines 11 – 12.
Regarding claim 8, ADAMS discloses that “the anti-CD38 antibody is administered or provided for administration in a pharmaceutical composition comprising about 1,800 mg of the anti-CD38 antibody and about 30,000 U of rHuPH20”. See ADAMS at claim 55.
Regarding claim 9, ADAMS discloses a GPRC5DxCD3 bispecific antibody with a GPRC5D binding domain with CDRs of SEQ ID NOs: 27 – 29 and 30 – 32 and with a CD3 binding domain with CDRs of SEQ ID NOs: 17 – 19 and 20 – 22 with 100% identity. See Appendix of record.
Regarding claim 10, ADAMS’ SEQ ID NO: 51 is identical to instant SEQ ID NO: 33; ADAMS’ SEQ ID NO: 52 wholly discloses instant SEQ ID NO: 34. See Appendix of record.
Regarding claim 12, ADAMS discloses an anti-CD38 antibody with HCDRs of SEQ ID NOs: 7 – 9 and LCDRs of SEQ ID NOs: 10 – 12. ADAMS’ SEQ ID NO: 12 discloses instant SEQ ID NOs: 7 – 9 with 100% identity, and ADAMS’ SEQ ID NO: 5 discloses instant SEQ ID NOs: 10 – 12 with 100% identity. See Appendix of record.
Regarding claim 13, ADAMS’ SEQ ID NO: 4 is identical to instant SEQ ID NO: 5; ADAMS’ SEQ ID NO: 5 is identical to instant SEQ ID NO: 6. See Appendix of record.
Regarding claim 17, ADAMS discloses that the subject is relapsed or refractory to a prior anti-cancer therapy with immunomodulatory agents. See claims 28 and 118.
Regarding claim 18, ADAMS discloses that the subject is relapsed or refractory to treatment with the anti-CD38 antibody, lenalinomide, bortezomib, pomalidomide, carfilzomib, elotozumab, ixazomib, melphalan or thalidomide, or any combination thereof. See claim 118.
Regarding claim 19, ADAMS discloses one or more anti-cancer therapies selected from the group consisting of lenalidomide, thalidomide, pomalidomide, bortezomib, carfilzomib, elotozumab, ixazomib, melphalan, dexamethasone or prednisone. See claim 148.
Regarding claim 20, ADAMS discloses that CD4+ T cell activation and degranulation was determined by increased surface expression of CD25 (activation). See Fig. 5 and paragraph 0027.
NEW REJECTION, NECESSITATED BY CLAIM AMENDMENTS
Claims 11 and 15 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over ADAMS in view of FERTIG as applied to claims 1, 3 – 6 and 8 – 21 above, and further in view of OFFIDANI (Offidani M, et al. Novel experimental drugs for treatment of multiple myeloma. Journal of experimental pharmacology. 2021 Mar 9:245-64; see PTO-892 submitted with this Office Action).
The teachings of ADAMS and FERTIG are discussed above and fully incorporated here. Although ADAMS in view of FERTIG renders the methods of claims 1 and 9 – 10, from which claim 11 depends, and the regimen of claim 15 obvious, neither ADAMS nor FERTIG teaches that the disclosed GPRC5DxCD3 bispecific antibody is talquetamab.
OFFIDANI is a review of the results of new therapies and their potential applications of new combinations of naked mAbs because they are becoming the therapy of choice for patients refractory to lenalidomide and/or proteasome inhibitors (PI). OFFIDANI teaches that CAR-T cells and bispecific mAbs have shown relevant results in very advanced stages of disease. See OFFIDANI at the abstract.
OFFINDANI teaches that by using monoclonal antibodies (mAbs) in different combinations, there has been an amazing improvement in the outcome of this disease in recent years. See OFFIDANI at the abstract
OFFIDANI teaches that new generation immunotherapies include bispecific monoclonal antibodies such as talquetamab. See OFFIDANI at p. 250, end of right column - p. 251, top of left column.
In addition, OFFIDANI teaches that daratumumab is the first fully human IgG1κ mAb targeting CD38 to be explored in MM after it showed antimyeloma activity as single agent. See OFFIDANI at p. 247, left column, second paragraph. Furthermore, OFFIDANI teaches the co-formulation of daratumumab (DARA SC) (1800 mg flat dose) with recombinant human hyaluronidase (rHuPH20). See OFFIDANI at p. 248, left column, first paragraph.
Thus, because OFFIDANI teaches that talquetamab and daratumumab each effectively treats MM and teaches that by using monoclonal antibodies (mAbs) in different combinations, there has been an improvement in the outcome of MM, it would have been obvious to combine talquetamab and daratumumab, as recited in claims 11 and 15, to treat MM.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of ADAMS, FERTIG, and OFFIDANI. The artisan would have been motivated to use the methods of claims 1 and 15 because ADAMS teaches methods that enhance T cell functionality for optimal efficacy of the therapeutics mediating T cell redirected killing (see ADAMS at paragraph 0005); FERTIG teaches T-cell bispecific antibodies targeting GPRC5D that have the potency to treat MM (see FERTIG at p. 2, lines 21 – 23); and OFFIDANI teaches that by using monoclonal antibodies (mAbs) in different combinations, there has been an amazing improvement in the outcome of MM (see OFFIDANI at the abstract). Thus, the artisan would have a reasonable expectation of success with the combined teachings of ADAMS, FERTIG, and OFFIDANI.
Regarding claim 16, FERTIG teaches that the administration of the bispecific antibody may be repeated over several days or longer, depending on the condition, the treatment would generally be sustained until a desired suppression of disease symptoms occurs. One exemplary dosage of the antibody or bispecific antigen binding molecule would be in the range from about 0.005 mg/kg to about 10 mg/kg. In other non-limiting examples, a dose may also comprise from about 1 microgram/kg body weight, about 5 microgram/kg body weight, about 10 microgram/kg body weight, about 50 microgram/kg body weight, about 100 microgram/kg body weight, about 200 microgram/kg body weight, about 350 microgram/kg body weight, about 500 microgram/kg body weight, about 1 milligram/kg body weight. See FERTG at p. 135, lines 25 – 32.
Response to Arguments
On p. 7, first paragraph – 10, first paragraph, of the reply of 06/01/2026, Applicant argues on the effectiveness of the claimed methods and presents preliminary results of phase 1b TRIMM 2 study.
Applicant’s argument and data have been fully considered. However, MPEP 2145 states that "[e]vidence pertaining to secondary considerations must be taken into account whenever it has been properly presented; however, it does not necessarily control the obviousness conclusion. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372, 82 USPQ2d 1321, 1339 (Fed. Cir. 2007) ('the record establish[ed] such a strong case of obviousness' that allegedly unexpectedly superior results were ultimately insufficient to overcome obviousness conclusion); Leapfrog Enterprises Inc. v. Fisher-Price Inc., 485 F.3d 1157, 1162, 82 USPQ2d 1687, 1692 (Fed. Cir. 2007) ("given the strength of the prima facie obviousness showing, the evidence on secondary considerations was inadequate to overcome a final conclusion" of obviousness); and Newell Cos., Inc. v. Kenney Mfg. Co., 864 F.2d 757, 768, 9 USPQ2d 1417, 1426 (Fed. Cir. 1988)."
Furthermore, FERTIG teaches that “other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques and assays” (see FERTIG at p. 136, lines 12 – 13), suggesting that the determination of dosing regimens is routine in the art.
On p. 10, last two paragraphs – p. 11, third paragraph, of the reply, Applicant argues that sections of the references pointed to in the Office action of 12/01/2025 do not expressly teach the claimed dosing regimen.
However, combinations of the teachings of the cited references render the claimed methods obvious as discussed above. MPEP 2144.05 states that “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of ‘having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium’ as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. ‘The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.’)”.
FERTIG teaches that “other dosage regimens may be useful. The progress of this therapy is
easily monitored by conventional techniques and assays” (see FERTIG at p. 136, lines 12 – 13), suggesting that the determination of dosing regimens is routine in the art. Because the combination of a GPRC5DxCD3 bispecific antibody and an anti-CD38 antibody is expressly taught by ADAMS (and suggested by FERTIG and OFFIDANI) and similar dosing regimens are taught by the cited references, one having ordinary skill in the art can arrive to the claimed dosing regimen by routine experimentation, which FERTIG suggests is common in the art.
On p. 10, last paragraph, of the reply, Applicant argues that “the portion of Adams I relied on by the Office fails to teach or suggest a combination of administration frequences, much less the claimed treatment dose of 1800 mg once every week during week 1 to week 8 of the treatment, once every two weeks during week 9 to week 24 of the treatment, and once every four weeks after week 24 of the treatment, as required by amended independent claims 1 and 15.”
However, ADAMS teaches that the anti-CD38 antibody is administered at about 1,800 mg (see ADAMS at claims 55 and 90) and that that the anti-CD38 antibody may be administered at weekly intervals for 8 weeks, followed by administration at every two weeks for an additional 16 weeks, followed by administration at every four weeks by intravenous infusion (see ADAMS at paragraph 0368). Thus, ADAMS renders the dose 1800 mg and the regimen of “once every week during week 1 to week 8 of the treatment, once every two weeks during week 9 to week 24 of the treatment, and once every four weeks after week 24 of the treatment” obvious, and it would have been obvious to one having ordinary skill in the art to administer the anti-CD38 antibody at a dose of 1800mg once every week during week 1 to week 8 of the treatment, once every two weeks during week 9 to week 24 of the treatment, and once every four weeks after week 24 of the treatment.
On p. 6, last paragraph, of the reply, Applicant argues that “a POSA would not have reasonably expected the presently claimed coordinated dosing regimen to achieve the demonstrated durable efficacy in heavily pretreated relapsed or refractory multiple myeloma patients, particularly patients previously exposed to T- cell redirecting therapies and bispecific antibodies. Clinical optimization of T-cell redirecting regimens is highly unpredictable due to cytokine release syndrome risk, T-cell exhaustion, refractory disease biology, immune dysregulation, tolerability considerations associated with repeated administration, and the difficulty in maintaining durable anti-tumor responses in heavily pretreated patients. The cited references do not provide a reasonable expectation that the presently claimed integrated dosing architecture would achieve the clinical efficacy and progression-free survival demonstrated in Applicant's disclosure and Chari.”
However, in the discussion of talquetamab (p. 250, right column, last paragraph) of OFFIDANI is a reference to CHARI (63. Chari A, et al. A phase 1, first-in-human study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl 1):abstract 290. doi:10.1182/blood-2020-133873; see PTO:892 submitted with this Office Action), which is directed to talquetamab (JNJ-64407564), which is a first-in-class bispecific antibody that binds to GPRC5D and CD3 to induce T cell-mediated killing of GPRC5D-expressing MM cells through the recruitment and activation of T cells (see CHARI at p. 2, first paragraph.
CHARI teaches weekly IV dosing (see CHARI at p. 2, last sentence) and that 3/4 responded at the 405 µg/kg SC dose (see CHARI at p. 3, second paragraph). Furthermore, CHARI teaches that “only grade 1 - 2 CRS was seen with SC dosing. CRS was generally confined to the first cycle with median time to onset of 1 day (1 - 3) for IV and 2 days (1 - 5) for SC dosing. Treatment-related neurotoxicity was reported in 7 (5%) pts (all resolved/resolving; median duration of 2 days [1 - 9]): 4 had grade 1 - 2 events and 3 had grade 3 events of delirium (n=1), decreased level of consciousness (n=1), or confusion (n=1). Six of 7 pts had neurotoxicity that occurred in the context of CRS, including all 3 grade 3 events. Infections were reported in 37% of pts (8% grade 3 - 4). Infusion related reactions (IV; 15%) and injection site reactions (SC; 14%) were grade 1 - 2 and generally occurred in cycle 1. Two dose-limiting toxicities were observed: clinically asymptomatic grade 4 increased lipase in the setting of a pancreatic plasmacytoma (7.5 µg/kg IV) and grade 3 maculopapular rash (135 µg/kg SC).”
Thus, CHARI teaches the benefits and side-effects of treatment of RRMM with talquetamab, rendering the claimed talquetamab dosing regimen obvious and the side-effects of talquetamab predictable and manageable.
Thus, the combined teachings of the cited references render the claimed methods obvious.
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, 3 – 6 and 8 – 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of U.S. Patent No. 11,685,777 in view of ADAMS, FERTIG, and OFFIDANI.
Patented claim 1 recites a An isolated GPRC5D x CD3 bispecific antibody comprising:
a) a first heavy chain (HC1); b) a second heavy chain (HC2); c) a first light chain (LC 1); and
d) a second light chain (LC2), wherein the HC1 and the LC1 pair to form a first antigen-binding site that specifically binds CD3, and the HC2 and the LC2 pair to form a second antigen-binding site that specifically binds GPRC5D; wherein the HC1 comprises the amino acid sequence of SEQ ID NO: 25 and the LC1 comprises the amino acid sequence of SEQ ID NO: 26, and wherein the HC2 comprises the amino acid sequence of SEQ ID NO: 55 and the LC2 comprises the amino acid sequence of SEQ ID NO: 58.
Patented SEQ ID NOs: 25, 55 and 58 disclose present SEQ ID NOs 23, 33 and 34 of present claim 10 with 100% identity. See Appendix of record. ADAMS discloses present SEQ ID NO: 24 of present claim 10 as discussed in the 103 rejection above.
The main difference between the present claims and the patented claims is that the present claims recite a method of administration of the GPRC5DxCD3 bispecific with an anti-CD38 antibody in the recited regimen. However, ADAMS, FERTIG, and OFFIDANI disclose this difference. The teachings of ADAMS, FERTIG, OFFIDANI, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a GPRC5D x CD3 bispecific antibody; ADAMS in view of FERTIG discloses that the GPRC5DxCD3 bispecific antibody may be administered with an anti-CD38 antibody (daratumubam) in the dosing regimen of the present claims; and OFFIDANI teaches that the GPRC5DxCD3 bispecific antibody is talquetamab, it would have been obvious to one having ordinary skill in the art to use the patented claims’ GPRC5DxCD3 bispecific antibody in the method of the present claims. There would have been a reasonable expectation of success considering that administering the GPRC5DxCD3 bispecific antibody alone or in combination with an anti-CD38 antibody is known to successfully treat cancer as evidenced by the applied prior art.
Claims 1, 3 – 6 and 8 – 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 28 of U.S. Patent No. 12,065,500 in view of ADAMS, FERTIG, and OFFIDANI.
Patented claim 1 recites a method of treating a multiple myeloma in a subject, comprising administering a therapeutically effective amount of an anti-CD38 antibody and a T cell redirecting therapeutic to the subject to treat the multiple myeloma, wherein the T cell redirecting therapeutic comprises: a CD3 binding domain and a BCMA binding domain.
The main difference between the present claims and the patented claims is that the present claims recite a GPRC5DxCD3 bispecific instead of the patented claims’ BCMAxCD3 bispecific antibody . However, ADAMS, FERTIG, and OFFIDANI disclose this difference. The teachings of ADAMS, FERTIG, OFFIDANI, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a method of treating a multiple myeloma in a subject, comprising administering a therapeutically effective amount of an anti-CD38 antibody and a BCMAxCD3 bispecific antibody, and ADAMS in view of FERTIG discloses a similar method with the GPRC5DxCD3 bispecific instead of BCMAxCD3 and OFFIDANI teaches that the GPRC5DxCD3 bispecific antibody is talquetamab, it would have been obvious to one having ordinary skill in the art to use the patented claims’ method with ADAMS’ GPRC5DxCD3 bispecific or OFFIDANI’s talquetamab and the dosing regimen rendered obvious by ADAMS in view of FERTIG to arrive to the method of the present claims.
Claims 1, 3 – 6 and 8 – 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 – 9, 11 – 18, and 24 – 32 of copending Application No. 17/477,435 in view of ADAMS and FERTIG.
Copending claim 8 recites a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising subcutaneously administering to the subject 400 µg/kg of a GPRC5DxCD3 bispecific antibody weekly, after the subject has been subcutaneously administered priming doses of the GPRC5DxCD3 bispecific antibody, wherein the priming doses comprise doses of 10 µg/kg and 60 µg/kg, and wherein the GPRC5DxCD3 bispecific antibody comprises a GPRC5D binding domain comprising a HCDR1 of SEQ ID NO: 4, a HCDR2 of SEQ ID NO: 5, a HCDR3 of SEQ ID NO: 6, a LCDR1 of SEQ ID NO: 7, a LCDR2 of SEQ ID NO: 8 and a LCDR3 of SEQ ID NO: 9, and a CD3 binding domain comprising a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 16, a LCDR1 of SEQ ID NO: 17, a LCDR2 of SEQ ID NO: 18 and a LCDR3 of SEQ ID NO: 19,wherein the method is effective in treating the multiple myeloma by achieving a stringent complete response, a complete response, a very good partial response, or a partial response in the subject, according to International Myeloma Working Group (IMWG) criteria.
Copending claim 11 recites that the GPRC5D binding domain comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 10 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 11, and the CD3 binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 20 and a VL having the amino acid sequence of SEQ ID NO: 21.
Copending claim 14 recites that the GPRC5DxCD3 bispecific antibody comprises a first heavy chain (HCl) having the amino acid sequence of SEQ ID NO: 12, a first light chain (LCl) having the amino acid sequence of SEQ ID NO: 13, a second heavy chain (HC2) having the amino acid sequence of SEQ ID NO: 22 and a second light chain (LC2) having the amino acid sequence of SEQ ID NO: 23.
Copending claim 15 recites that the GPRC5DxCD3 bispecific antibody is talquetamab.
Copending claim 24 recites that the GPRC5D binding domain comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 10 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 11, and the CD3 binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 20 and a VL having the amino acid sequence of SEQ ID NO: 21.
Copending SEQ ID NOs: 10 – 13 and 20 – 23 discloses present SEQ ID NOs: 33 - 34, 23 – 26, and 35 – 36, respectively, with 100% identity. See Appendix.
The main difference between the present claims and the copending claims is that the present claims recite the addition an anti-CD38 antibody to the claimed method. However, ADAMS in view of FERTIG discloses this difference. The teachings of ADAMS and FERTIG, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the copending claims recite recites a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising subcutaneously administering to the subject 400 µg/kg of a GPRC5DxCD3 bispecific antibody weekly, after the subject has been subcutaneously administered priming doses of the GPRC5DxCD3 bispecific antibody, wherein the priming doses comprise doses of 10 µg/kg and 60 µg/kg, and ADAMS in view of FERTIG teaches that the GPRC5DxCD3 bispecific antibody may be administered with an anti-CD38 antibody in the dose regimen of the present claims, it would have been obvious to one having ordinary skill in the art to use the copending claims’ method with an anti-CD38 antibody and dosing regimen as taught by ADAMS in view of FERTIG to arrive to the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
On p. 12 of the reply of 06/01/2026 and in response to the double patenting rejections, Applicant argues that “[b]ecause the claims of the pending application are otherwise allowable for the reasons noted above with respect to the combination of Adams and Fertig, Applicant respectfully requests that this rejection be withdrawn for at least the same reasons.”
However, the presently claimed methods are rendered obvious by ADAMS, FERTIG, and OFFIDANI, as discussed in the 103 rejections above, and by the patented or copending claims in view of ADAMS, FERTIG, and OFFIDANI, as discussed in the double patenting rejections above. Thus, the pending double patenting rejections are maintained.
In view of the later filing date of copending application 18/208,361, the provisional rejection of the present claims on the ground of nonstatutory double patenting as being unpatentable over copending 18/208,361 is withdrawn.
Conclusion
Claims 1, 3 – 6 and 8 – 21 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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