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 .
Application Status
Claims 1-92 are pending and examined on the merits herein.
Information Disclosure Statement
The references cited on the information disclosure statements filed 06/13/2025 (#2), 09/04/2025, 10/21/2025, 01/06/2026, 07/22/2026 (#1 and #3) were considered and have been made of record to the extent that each was provided.
The information disclosure statements filed 06/13/2025 (# 1 and #3), 07/22/2026 (#2 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Drawings
The drawings are objected to because the legends and labels on multiple figures are not in the English language and are therefore not able to be examined.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 21. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-38, 40, 42, 46-47, 51-53, 55-56, 64, 77-79, 87, 89, and 91 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBank Teclistamab (ID: DB16655; created March 24, 2021 and updated August 05, 2026; Herein “Teclistamab”; PTO-892) and DrugBank Talquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892).
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 2-14, as evidenced by Teclistamab, the sequence of the BCMAxCD3 IgG4 antibody teclistamab has 100% sequence identity to the instant claimed SEQ ID NO: 4-23 which contain the recited Fc substitutions.
Regarding claims 16-28, as evidenced by Talquetamab, the sequence of the GPRC5DxCD3 IgG4 antibody talquetamab has 100% sequence identity to the instant claimed SEQ ID NO: 14-23 and 30-33 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
Claim Rejections - 35 USC § 103
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.
Claim(s) 39, 43-44, 49-50, 57-58, 61-62, 67-69, 71, 80-86, 88, 90, and 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBank Teclistamab (ID: DB16655; created March 24, 2021 and updated August 05, 2026; Herein “Teclistamab”; PTO-892) and DrugBankTalquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892) as applied to claims 1-38, 40, 42, 46-47, 51-53, 55-56, 64, 77-79, 87, 89, and 91 above, and further in view of Moreau (New Engl J Med, 2022, 387(6): 495-505; IDS entered 06/13/2025; supplements attached as NPL), Berdeja (ASCO annual meeting, 2021, June 4-8; IDS entered 06/13/2025) and Ball (MABS, 2023, 15(1):2181016; IDS entered 07/22/2026).
The teachings of Cho regarding claims 1-38, 40, 42, 46-47, 51-53, 55-56, 64, 77-79, 87, 89, and 91 are detailed above.
Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution such as talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) which are being evaluated for RRMM (perspectives para 2; Table 3).
Cho does not teach biweekly dosing of teclistamab or the timing of the step up doses.
Regarding claims 39, 42-44, and 61-62, Moreau teaches that for any subjects receiving weekly dosing, a change from the weekly dosing to biweekly dosing schedule may occur, if approved when: A subject has had a minimum of 6 months of therapy and they achieve a minimum response of CR or a subject has maintained a response of <CR for at least a year (page 214).
Regarding claims 49 and 67-68, Moreau teaches that the step-up doses were separated by 2 to 4 days and were completed 2 to 4 days before the administration of the first full teclistamab dose (page 496, col 2, para 2).
Regarding claims 80, 82, 84, 88, 90, and 92, Moreau teaches that response rates were lower in patients with extramedullary disease (page 499, col 1, para 1), which probably reflects the poor prognosis in this population, which is historically challenging to treat (page 503, col 1, para 1). Moreau further teaches that EMD patients had 10/28 responders (35.7%) albeit with a wide confidence interval (Fig S2).
Regarding claim 50, 57-58, 67-69 and 71, Berdeja teaches with 10.0 and 60.0 µg/kg step-up doses for talquetamab (abstract; results).
Regarding claims 50, 57, and 67-68, Ball teaches for the currently approved T cell engagers (TCEs), a key discovery was that by incrementally increasing the dose administered to a patient before reaching the target dose level, the body’s immune system could be primed in a more gradual manner, thereby modulating the balance between T cell activation and expansion, and cytokine-mediated efficacy and toxicity, which is known as step up dosing (Intro; para 2).
Regarding claims 41, 48, 54, 59-60, 63, 65-66, 70, and 72-76, Ball teaches it is essential to develop rational, mechanistically guided approaches to dose selection and clinical study design, in order to facilitate the development of immune engaging molecules with a better therapeutic index in patients (page 14, col 1, para 2; Fig 3). Ball further teaches current approaches to select optimal dose regimens within clinical studies of TCEs are then evaluated, and alternative strategies are considered (intro; para 4). Ball further teaches as clinical development progresses, population PK/PD and exposure-response modeling can help to determine appropriate step-up and target dose regimens for further evaluation in pivotal trials and in additional patient populations, as demonstrated for mounetuzumab, glofitinib, and blinatumomab (page 9, col 2, para 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to incorporate a step up dose for talquetamab as taught by Berdeja and timing for the step up doses for teclistamab as taught by Moreau in the method of treating multiple myeloma with teclistamab and talquetamab as taught by Cho and further to optimize dosing amount and timing as taught by Ball. The ordinary artisan would have been motivated to do so because Moreau and Berdeja teach additional steps in the protocol for administration of teclistamab and talquetamab and Ball teaches a key discovery was that by incrementally increasing the dose administered to a patient before reaching the target dose level for TCE to avoid CRS. Further, as Moreau teaches that response rates were lower in patients with extramedullary disease with only teclistamab, which probably reflects the poor prognosis in this population, the ordinary artisan would be motivated to combine talquetamab and teclistamab to improve clinical outcomes as taught by Cho.
Regarding claims 41, 48, 54, 59-60, 63, 65-66, 70, and 72-76, as taught by Ball essential to develop rational, mechanistically guided approaches to dose selection and clinical study design, in order to facilitate the development of immune engaging molecules with a better therapeutic index in patients and would do this using population PK/PD and exposure-response modeling can help to determine appropriate step-up and target dose regimens. Therefore one of ordinary skill in the art would have a reasonable expectation of success to test various doses and timing of administrations to as necessary to establish an effective treatment protocol for RRMM patients while minimizing toxicity.
Further, one of ordinary skill in the art would recognize antibody concentration
and timing of administration as result-effective variables and optimize them by 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 re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As
set forth at MPEP 2144.05 II. A: “Generally, differences in concentration or temperature
will not support the patentability of subject matter encompassed by the prior art unless
there is evidence indicating such concentration or temperature is critical.”
Further, regarding claims 80-92, applicant is reminded that chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). A person of ordinary skill in the art would recognize that these are properties of the combination therapy of teclistamab and talquetamab.
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 1-38, 40, 42, 46-48, 51-53, 55-56, 63-64, and 77-79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 12-13 of U.S. Patent No. 11,952,426 B2 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBank Talquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892).
Regarding claims 1-3, 30, 38, 40, 42, and 63, the patented claims teach a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising administering a therapeutically effective amount of a BCMAxCD3 bispecific antibody to the subject to treat the cancer, wherein the subject is relapsed or refractory to treatment with at least one prior anti-cancer treatment, wherein the BCMAxCD3 bispecific antibody comprises a BCMA binding domain comprising 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 a CD3 binding domain comprising 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, wherein the BCMAxCD3 bispecific antibody is administered subcutaneously at a dose of about 1500 μg/kg weekly, and wherein the method is effective in treating the multiple myeloma (claim 1). SEQ ID NOs: 10, 11, 20, and 21 have 100% sequence identity to the same instant claimed SEQ ID NOs.
Regarding claims 4-5, the patented claims teach wherein the BCMAxCD3 bispecific antibody is an IgG4 isotype (claim 2).
Regarding claims 11-14, the patented claims teach wherein the BCMAxCD3 bispecific antibody comprises a first heavy chain (HC1) having the amino acid sequence of SEQ ID NO: 12, a first light chain (LC1) 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 (claim 3). SEQ ID NOs: 12, 13, 22, and 23 have 100% sequence identity to the same instant claimed SEQ ID NOs.
Regarding claims 6-10 and 15, the patented claims teach wherein the BCMAxCD3 bispecific antibody is teclistamab (claim 4).
Regarding claims 31 and 34, the patented claims teach wherein the subject is relapsed or refractory to treatment with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody (claim 12).
Regarding claims 37 and 46-48, the patented claims teach wherein step-up doses of about 60 μg/kg and about 300 μg/kg are administered to the subject prior to the dose of about 1500 μg/kg weekly (claim 13).
Regarding claim 77, the patented claims teach wherein the BCMAxCD3 bispecific antibody is administered for a time sufficient to achieve complete response, stringent complete response, very good partial response, partial response, minimal response or stable disease status, and can be continued until disease progression or lack of patient benefit (claim 5).
The patented claims do not teach treatment by administering an effective amount of a GPRC5DxCD3 bispecific antibody.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 16-28, as evidenced by Talquetamab, the sequence of the GPRC5DxCD3 IgG4 antibody talquetamab has 100% sequence identity to the instant claimed SEQ ID NO: 14-23 and 30-33 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the patented claims and GPRC5DxCD3 antibody treatment regimens as taught by Cho. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquetamab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Claims 1-17, 20-38, 40, 42, 46-47, 50-53, 55-59, 64, 70, 77-79, 87, 89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-9, 11-15, 24-28, and 32 of copending Application No. 17/477,435 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBank Teclistamab (ID: DB16655; created March 24, 2021 and updated August 05, 2026; Herein “Teclistamab”; PTO-892).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 16, 30, 50-51, 53, 55, 57-59, 64, and 77, the copending claims teach 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 p.g/kg and 60 p.g/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 (claim 8).
Regarding claims 16, 30, 50, 52, 56-58, and 77, the copending claims teach a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising subcutaneously administering to the subject 800 p.g/kg of a GPRC5DxCD3 bispecific antibody biweekly, after the subject has been subcutaneously administered priming doses of the GPRC5DxCD3 bispecific antibody, wherein the priming doses comprise doses of 10 p.g/kg and 60 p.g/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 (IIMWG) criteria (claim 9).
Regarding claims 17, wherein 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 (claim 11 and 24).
Regarding claim 20, the copending claims teach wherein the GPRC5DxCD3 bispecific antibody is an IgG4 isotype having a first heavy chain (HC1) and a second heavy chain (HC2), and the antibody comprises leucine at position 405 and lysine at position 409 in the second heavy chain (HC2), wherein residue numbering is according to the EU Index (claim 12 and 25).
Regarding claim 21-24, the copending claims teach wherein the GPRC5DxCD3 bispecific antibody further comprises proline at position 228, alanine at position 234 and alanine at position 235 in both the HC1 and the HC2 (claim 13 and 26).
Regarding claim 25-28, the copending claims teach wherein the GPRC5DxCD3 bispecific antibody comprises a first heavy chain (HC1) having the amino acid sequence of SEQ ID NO: 12, a first light chain (LC1) 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 (claim 14 and 27).
Regarding claims 20-24 and 29, the copending claims teach wherein the GPRC5DxCD3 bispecific antibody is talquetamab (claim 15 and 28).
Regarding claim 50 and 70, the copending claims teach wherein the priming doses comprise doses of 10 pg/kg and 60 pg/kg and 300 pg/kg (claim 32).
The copending claims do not teach combination treatment with teclistamab.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 2-14, as evidenced by Teclistamab, the sequence of the BCMAxCD3 IgG4 antibody teclistamab has 100% sequence identity to the instant claimed SEQ ID NO: 4-23 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the Cho and GPRC5DxCD3 antibody treatment regimens as taught by the copending claims. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquatemab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Claims 1 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 36-37, 39, 41-43, and 61-69 of copending Application No. 17/672,123 (U.S. Patent 12,637,509 which has not yet been published).
This is a provisional nonstatutory double patenting rejection.
The instant claims are drawn to a method of treatment for multiple myeloma comprising teclistamab (BCMAxCD3) and talquetamab (GPRC5DxCD3).
The copending claims are drawn to a trispecific antibody that targets GPRC5DxBCMAxCD3 used in a method of treating multiple myeloma. Although the antibody sequences are not the same, instant claim 1 is generic and would be anticipated by the patented claims as would dependent claim 30 that is drawn to RRMM.
Claims 1-40, 42-43, 45-48, 51-53, 55-56, 64, 77-79, 87, 89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-23, 25-27, 29-35, and 37-41 of copending Application No. 18/439,951 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBankTalquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 1-3, 11-14, 37-38, 40, 42, and 46, the copending claims teach a method of treating multiple myeloma in a human subject in need thereof, comprising subcutaneously administering a therapeutically effective amount of a BCMAxCD3 bispecific antibody to the subject to treat the multiple myeloma, wherein the BCMAxCD3 bispecific antibody comprises a BCMA binding domain comprising a first heavy chain (HC 1) having the amino acid sequence of SEQ ID NO: 12 and a first light chain (LC 1) having the amino acid sequence of SEQ ID NO: 13, and a CD3 binding domain comprising 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, wherein the method comprises administering two step-up doses of the BCMAxCD3 bispecific antibody followed by at least two 1500 pg/kg treatment doses of the BCMAxCD3 bispecific antibody, wherein said at least two treatment doses are administered about one week apart from each other, and wherein the method is effective in treating the multiple myeloma (claim 22).
Regarding claims 4-5, the copending claims teach wherein the BCMAxCD3 bispecific antibody is an IgG4 isotype (claim 23).
Regarding claim 6-10 and 15, the copending claims teach wherein the BCMAxCD3 bispecific antibody is teclistamab (claim 25)
Regarding claim 30, the copending claims teach wherein the subject is relapsed or refractory to treatment with at least one prior anti-cancer treatment (claim 27 and 35).
Regarding claims 31 and 34, the copending claims teach wherein the subject is relapsed or refractory to treatment with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody (claim 29 and 37).
Regarding claims 39, 43, 45, and 48, the copending claims teach wherein, after the at least two 1500 pg/kg treatment doses are administered about one week apart from each other, additional treatment doses of the BCMAxCD3 bispecific antibody are administered in amounts of up to 3000 pg/kg (claim 31 and 39), wherein, after the at least two 1500 pg/kg treatment doses are administered about one week apart from each other, additional treatment doses of the BCMAxCD3 bispecific antibody are administered once every two weeks, or once every three weeks, or once every month (claim 32-33 and 40-41).
Regarding claim 47, the copending claims teach wherein the two step-up doses are administered in amounts of 60 pg/kg and 300 pg/kg (claim 30 and 38).
Regarding claim 77, the copending claims teach wherein the BCMAxCD3 bispecific antibody is administered for a time sufficient to achieve a complete response, a stringent complete response, a very good partial response, or a partial response, according to International Myeloma Working Group (IMWG) criteria (claim 26 and 34).
The copending claims do not teach treatment by administering an effective amount of a GPRC5DxCD3 bispecific antibody.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 16-28, as evidenced by Talquetamab, the sequence of the GPRC5DxCD3 IgG4 antibody talquetamab has 100% sequence identity to the instant claimed SEQ ID NO: 14-23 and 30-33 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the copending claims and GPRC5DxCD3 antibody treatment regimens as taught by Cho. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquatemab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Claims 1-40, 42-43, 45-49, 51-53, 55-56, 60, 64, 77-79, 87, 89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 101-109, 111-116, and 118 of copending Application No. 18/639,242 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBankTalquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 1-15 and 38-39, the copending claims teach a method of treating multiple myeloma in a subject in need thereof, comprising subcutaneously administering to the subject treatment doses of a BCMAxCD3 bispecific antibody on a weekly dosing schedule (QW) for at least one 28-day treatment cycle, and subsequently administering to the subject treatment doses of the BCMAxCD3 bispecific antibody on a bi-weekly dosing schedule (Q2W) for at least one 28-day treatment cycle, and subsequently administering to the subject treatment doses of the BCMAxCD3 bispecific antibody on a monthly dosing schedule (Q4W), wherein the BCMAxCD3 bispecific antibody comprises a BCMA binding domain comprising the HCDR1 of SEQ ID NO: 4, the HCDR2 of SEQ ID NO: 5, the HCDR3 of SEQ ID NO: 6, the LCDR1 of SEQ ID NO: 7, the LCDR2 of SEQ ID NO: 8 and the LCDR3 of SEQ ID NO: 9, and a CD3 binding domain comprising the HCDR1 of SEQ ID NO: 14, the HCDR2 of SEQ ID NO: 15, the HCDR3 of SEQ ID NO: 16, the LCDR1 of SEQ ID NO: 17, the LCDR2 of SEQ ID NO: 18 and the LCDR3 of SEQ ID NO: 19, and wherein the method is effective in treating the multiple myeloma (claim 101), wherein the BCMAxCD3 bispecific antibody is teclistamab (claims 102-104).
Regarding claim 30, the copending claims teach wherein the subject has relapsed or refractory multiple myeloma (claim 105 and 112)
Regarding claim 37, the copending claims teach comprising subcutaneously administering to the subject one or more step-up doses of the BCMAxCD3 bispecific antibody prior to administering the first treatment dose of the BCMAxCD3 bispecific antibody (claim 106 and 113).
Regarding claims 40, 42-43, 45 the copending claims teach comprising administering the BCMAxCD3 bispecific antibody on the weekly dosing schedule (QW) at a treatment dose of about 1500 pg/ kg, and administering the BCMAxCD3 bispecific antibody on the bi-weekly dosing schedule (Q2W) at a treatment dose of about 3000 pg/kg (claim 107-108 and 114-115).
Regarding claim 46-49 and 61, the copending claims teach comprising administering the BCMAxCD3 bispecific antibody in the following 28-day treatment cycles: Cycle 1: 0.06 mg/kg step-up dose on Day 2, 0.3 mg/kg step-up dose on Day 4, 1.5 mg/kg step-up dose (also referred to as a treatment dose) on Day 8 and 1.5 mg/kg weekly (QW) thereafter;Cycle 2: 1.5 mg/kg weekly (QW);Cycles 3-6: 3 mg/kg biweekly (Q2W);Cycle 7 and subsequent cycles: 3 mg/kg monthly (Q4W) (claim 111 and 118).
Regarding claim 77, the copending claims teach wherein the subject achieves a clinical response that is a partial response (PR), or a very good partial response (VGPR), or a complete response (CR) or a stringent complete response (sCR) according to International Myeloma Working Group (IMWG) criteria (claim 109 and 116).
The copending claims do not teach treatment by administering an effective amount of a GPRC5DxCD3 bispecific antibody.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 16-28, as evidenced by Talquetamab, the sequence of the GPRC5DxCD3 IgG4 antibody talquetamab has 100% sequence identity to the instant claimed SEQ ID NO: 14-23 and 30-33 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the copending claims and GPRC5DxCD3 antibody treatment regimens as taught by Cho. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquatemab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Claims 1-38, 40, 42, 45-49, 51-53, 55-56, 60, 64, 77-79, 87, 89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 19, 21, 26-33, 38-39, 49, 53-55, and 60 of copending Application No. 19/581,761 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBankTalquetamab (ID: DB16678; created April 01, 2021 and updated October 30, 2025; herein “Talquetamab”; PTO-892).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the copending claims teach a method of treating high-risk smoldering multiple myeloma (HR-SMM) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a BCMAxCD3 bispecific antibody (claim 1).
Regarding claim 2, the copending claims teach wherein the BCMAxCD3 bispecific antibody comprises a BCMA binding domain comprising the HCDR1 of SEQ ID NO: 4, the HCDR2 of SEQ ID NO: 5, the HCDR3 of SEQ ID NO: 6, the LCDR1 of SEQ ID NO: 7, the LCDR2 of SEQ ID NO: 8 and the LCDR3 of SEQ ID NO: 9, and a CD3 binding domain comprising the HCDR1 of SEQ ID NO: 14, the HCDR2 of SEQ ID NO: 15, the HCDR3 of SEQ ID NO: 16, the LCDR1 of SEQ ID NO: 17, the LCDR2 of SEQ ID NO: 18 and the LCDR3 of SEQ ID NO: 19 (claim 2).
Regarding claim 3, wherein the BCMA 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 heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 21 (claim 3).
Regarding claims 4-5, the copending claims teach wherein the BCMAxCD3 bispecific antibody is an IgG4 isotype (claims 4-5).
Regarding claims 6-10, the copending claims teach wherein the Fe region of the CD3 binding arm comprises Proline/Alanine/Alanine substitutions at amino acid positions 228/234/235, respectively, in addition to F405L and R409K substitutions (claims 6-10).
Regarding claims 11-14, the copending claims teach wherein the BCMAxCD3 bispecific antibody comprises a first heavy chain (HC 1) having the amino acid sequence of SEQ ID NO: 12, a first light chain (LC1) 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 (claims 11-14).
Regarding claim 15, the copending claims teach wherein the BCMAxCD3 bispecific antibody is teclistamab (claim 15).
Regarding claim 37, the copending claims teach comprising subcutaneously administering each dose of the BCMAxCD3 bispecific antibody (claim 19), wherein one or more step-up doses of the BCMAxCD3 bispecific antibody are subcutaneously administered to the subject during a step-up phase (claim 21).
Regarding claims 38, 40, and 42, the copending claims teach wherein the regimen comprises:in Cycle 1, subcutaneously administering one or more step-up doses and then two or more weekly (QW) treatment doses, and in one or more subsequent BCMAxCD3 treatment cycles, subcutaneously administering weekly (QW) treatment doses (claim 49), wherein each treatment dose of the BCMAxCD3 bispecific antibody is administered to the subject in an amount of 1.5 mg/kg or 3 mg/kg (claim 53-54).
Regarding claim 45, the copending claims teach comprising administering the BCMAxCD3 bispecific antibody according to a regimen comprising 28-day cycles, wherein the regimen comprises:in Cycle 1, subcutaneously administering one or more step-up doses and then two or more weekly (QW) treatment doses of 1.5 mg/kg, and in one or more subsequent BCMAxCD3 treatment cycles, subcutaneously administering weekly (QW) treatment doses of 1.5 mg/kg, and then in one or more subsequent BCMAxCD3 treatment cycles, subcutaneously administering bi-weekly (Q2W) treatment doses of 3.0 mg/kg (claim 55).
Regarding claims 46-47, the copending claims teach wherein the step-up phase comprises a first step-up dose of 0.06 mg/kg of the BCMAxCD3 bispecific antibody and a second step-up dose of 0.3 mg/kg of the BCMAxCD3 bispecific antibody (claim 26-31).
Regarding claim 48, the copending claims teach wherein one or more treatment doses of the BCMAxCD3 bispecific antibody are subcutaneously administered to the subject during the step-up phase, in addition to the one or more step-up doses (claim 27), wherein each of the one or more treatment doses of the BCMAxCD3 bispecific antibody administered during the step-up phase are administered in an amount of 1.5 mg/kg (claims 32-33).
Regarding claim 49, the copending claims teach wherein the second step-up dose is administered 2-4 days after first step-up dose (claims 38-39).
Regarding claim 60, the copending claims teach wherein the wherein the method achieves a clinical response in the subject that is a partial response (PR), a very good partial response (VGPR), a complete response (CR) or a stringent complete response (sCR), as defined by IMWG (2016) response criteria (claim 60).
The copending claims do not teach treatment by administering an effective amount of a GPRC5DxCD3 bispecific antibody.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 16-28, as evidenced by Talquetamab, the sequence of the GPRC5DxCD3 IgG4 antibody talquetamab has 100% sequence identity to the instant claimed SEQ ID NO: 14-23 and 30-33 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the copending claims and GPRC5DxCD3 antibody treatment regimens as taught by Cho. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquatemab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Claims 1-38, 40, 42, 46-47, 50-53, 55-59, 64, 69-71, 77-79, 87, 89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 9-12, 15 and 17 of copending Application No. 19/783,743 in view of Cho (Front. Oncol., 2022, 12:1032775; PTO-892) as evidenced by DrugBank Teclistamab (ID: DB16655; created March 24, 2021 and updated August 05, 2026; Herein “Teclistamab”; PTO-892).
Regarding claims 1, 16-30, 50-51, 53, 55, 57-59, 69, 71, and 77, the copending claims teach a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising subcutaneously administering to the subject 400 pg/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 pg/kg and 60 pg/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 (claim 1 and 7), wherein the GPRC5DxCD3 bispecific antibody is talquetamab (claims 2-5).
Regarding claims 52 and 56, the copending claims teach a method of treating relapsed or refractory multiple myeloma in a human subject in need thereof, comprising subcutaneously administering to the subject 800 pg/kg of a GPRC5DxCD3 bispecific antibody biweekly, after the subject has been subcutaneously administered priming doses of the GPRC5DxCD3 bispecific antibody, wherein the priming doses comprise doses of 10 pg/kg and 60 pg/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 (claim 9 and 15), wherein the GPRC5DxCD3 bispecific antibody is talquetamab (claims 10-12).
Regarding claim 70, the copending claims teach wherein the priming doses comprise doses of 10 pg/kg and 60 pg/kg and 300 pg/kg (claim 17).
The copending claims do not teach combination treatment with teclistamab.
Regarding claims 1, 15, and 29-30, Cho teaches that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are under evaluation in RRMM patients (NCT04586426) (perspectives para 2; Table 3).
Regarding claims 2-14, as evidenced by Teclistamab, the sequence of the BCMAxCD3 IgG4 antibody teclistamab has 100% sequence identity to the instant claimed SEQ ID NO: 4-23 which contain the recited Fc substitutions.
Regarding claim 31-32 and 34-35, Cho teaches talquetamab was granted Breakthrough Therapy Designation (BTD) by the FDA in July 2022 for the treatment of adult patients with RRMM who have previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (page 6, col 1, para 1).
Regarding claim 33, Cho teaches teclistamab was tested on RRMM patients with 5 prior lines of treatment (table 1, page 9).
Regarding claims 36 and 78, Cho teaches that 17% of patients treated with teclistamab had extramedullary disease (EMD) (Table 1; teclistamab).
Regarding claims 37 and 46-47, Cho teaches weekly step up doses of 0.06 and 0.3 mg/kg (table 1; teclistamab).
Regarding claims 38, 40, 42, 64, Cho teaches teclistamab was administered subcutaneously at a weekly dose range 80−3000 μg/kg with an overall response rate of 63% (page 4, col 2, para 2) and further a specific dose of 1.5mg/kg (table 1; teclistamab).
Regarding claims 51-53, 55-56, 64, and 79, Cho teaches talquetamab was administered subcutaneously at 405 μg/kg QW [n = 30] or 800 μg/kg Q2W [n = 44] in clinical trial with an overall response rate of 70% (page 6, col 1, para 1).
Regarding claim 77, 87, 89, and 91, Cho teaches 97 (58.8%) very good partial response (VGPR) and a complete response rate of 65 (39.4%) to teclistamab (table 1, teclistamab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine BCMAxCD3 as taught by the Cho and GPRC5DxCD3 antibody treatment regimens as taught by the copending claims. The ordinary artisan would have been motivated to do so because Cho teaches that to reduce the risk of low antigen expression or antigen loss–related relapse, combining bispecific molecules that target different tumor antigens would be a logical solution and that talquetamab (anti-BCMA) and teclistamab (anti-GPRC5D) are already being tested for RRMM. Further Cho teaches that talquatemab and teclistamab have both demonstrated good efficacy and been approved separately by the EMA and FDA for treatment of MM. The ordinary artisan has a reasonable expectation of success to combine teclistamab and talquetamab at known effective dosing regimens to improve clinical outcomes for multiple myeloma patients.
As stated in the above rejection, each of these combinations had been taught by
the prior art to be effective in improving clinical outcomes in subjects with multiple
myeloma, the instant situation is amenable to the type of analysis set forth in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie
obvious to combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition which is to be used for
the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169
USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-
77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, it is prima facie obvious to combine the two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose of improving response in subjects with multiple myeloma.
Conclusion
No claims are allowed.
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/AMBER K FAUST/ Examiner, Art Unit 1643
/GARY B NICKOL/ Primary Examiner, Art Unit 1643
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