DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The rejection of claims 70-73, 75-80 and 82-83 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-14,19, 20, 23 and 24 of U.S. Patent No. 11,384,153 B2 (‘153) in view of ClinicalTrial.gov study NCT03761108 (https://clinicaltrials.gov/ct2/history/NCT03761108?A=1&B=1&C=merged#StudyPageTop, v.1, 11/29/2018, cited in the IDS filed 11/6/204) and Topp et al. (Blood, 132(Suppl. 1):1010, 29 Nov 2018) is withdrawn in view of the amendment requiring 3 increasing doses of bispecific antibody, which neither the patent claims nor the clinical study teach or makes obvious. Topp et al. taught administering one of a different selected dose of a bispecific anti-BCMAxanti-CD3 antibody different from one of the instant claims, with patients showing complete responses or partial remission at 400μg/d (fifth and sixth paragraph). Three patients at lower doses also obtained complete remission (sixth paragraph). Topp et al. does not support the obviousness of administering at least 3 increasing doses of the bispecific antibody to the same patient.
The rejection of claims 70-73, 75-80 and 82-83 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 6-8 of U.S. Patent No. 12,258,412 B2 (“412) in view of ClinicalTrial.gov study NCT03761108 (https://clinicaltrials.gov/ct2/history/NCT03761108?A=1&B=1&C=merged#StudyPageTop, v.1, 11/29/2018, cited in the IDS filed 11/6/204) and Topp et al. (Blood, 132(Suppl. 1):1010, 29 Nov 2018) is withdrawn for the reasons discussed immediately above for the nonstatutory double patenting rejection over claims of US Patent 11,384,153 B2.
The rejection of claims 70-76 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 41-49 and 52-59 of copending Application No. 18/765,008 (‘008) in view of in view of ClinicalTrial.gov study NCT03761108 (https://clinicaltrials.gov/ct2/history/NCT03761108?A=1&B=1&C=merged#StudyPageTop, v.1, 11/29/2018, cited in the IDS filed 11/6/204) and Topp et al. (Blood, 132(Suppl. 1):1010, 29 Nov 2018) is withdrawn for the reasons discussed immediately above for the nonstatutory double patenting rejection over claims of US Patent 11,384,153 B2.
The rejection of claim(s) 70-75 under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over ClinicalTrials.gov Study NCT03761108 (https://clinicaltrials.gov/ct2/history/NCT03761108?A=1&B=1&C=merged#StudyPageTop, v.1, 11/29/2018, cited in the IDS filed 11/6/204) in light of Applicant’s admission in paragraph [0190] of the instant specification is withdrawn in view of the amendment requiring 3 increasing doses of bispecific antibody, which the clinical study neither teaches nor makes obvious.
The rejection of claim(s) 77-82 under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials.gov Study NCT04083534 (https://clinicaltrials.gov/ct2/history/NCT04083534?A=1&B=1&C=merged#StudyPageTop, v.1, 09/05/2019, cited in the IDS filed 11/06/2024) in light of Applicant’s admission in paragraph [0191] of the instant specification is withdrawn in view of the amendment requiring 3 increasing doses of bispecific antibody, which the clinical study neither teaches nor makes 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 70-76 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,919,965 B2 (’965). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and patent claim a method of treating triple or up to penta-refractory multiple myeloma (MM) in a patient by administering a bispecific antibody (bsAb) binding BCMA and CD3 (claims 3-6 of ‘965 and instant claims 70 and 76). Both this application and the patent recite the same bispecific antibody in the claims, i.e.,the antibody has the same CDRs and heavy and light chain variable regions (HCVR and LCVR), HCVR of SEQ ID NO:66 and 90 and common LCVR of SEQ ID NO:82 (claim 1 of ‘965, and instant claim 70-73). The constant heavy chains and light chain are SEQ ID NO: 126-127 and 129, respectively (claim 2 of ‘965 and instant claim 74). The patent and instant application claim wherein the subject to be treated has received at least 3-5 prior therapies for MM (claims 3-6 of ‘965 and instant claims 70 and 76). The patent and instant application further claim wherein the prior therapies include an anti-CD38 antibody, a proteasome inhibitor and in an immunomodulatory drug (instant claim 70 and claims 7-13 of ‘965). The patent and instant application claim that the subject has a MM immune subtype of immunoglobulin (Ig) G, Ig A, lamda or kappa light chain or an extramedullary plasmacytoma (claims 14-15 of ‘965 and instant claim 75). Both the patent and instant application claim wherein the bispecific antibody is administered in a dosing regimen wherein the initial dose, administered during the first week, is less than the subsequent second dose, which is itself less than the subsequent third dose (claim 1 of ‘965 and instant claim 70).
Applicant states (bottom of p. 24 of REMARKS) that Applicant will consider submission of a terminal disclaimer, if appropriate, upon indication that the claims are otherwise allowable. While this statement is acknowledged, the Examiner cannot hold the rejection in abeyance and as indicated in the attached Interview Summary, Applicant did not wish to file a terminal disclaimer at this time. Therefore, the rejection is maintained.
Claims 70-76 remain and new claims 84-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,919,965 B2 (’965) as applied to claims 70-76 above, and further in view of US Patent 11,466,094 B2 (Chu).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and patent claim a method of treating triple or up to penta-refractory multiple myeloma (MM) in a patient by administering a bispecific antibody (bsAb) binding BCMA and CD3 (claims 3-6 of ‘965 and instant claims 70 and 76). Both this application and the patent recite the same bispecific antibody in the claims, i.e.,the antibody has the same CDRs and heavy and light chain variable regions (HCVR and LCVR), HCVR of SEQ ID NO:66 and 90 and common LCVR of SEQ ID NO:82 (claim 1 of ‘965, and instant claim 70-73). The constant heavy chains and light chain are SEQ ID NO: 126-127 and 129, respectively (claim 2 of ‘965 and instant claim 74). The patent and instant application claim wherein the subject to be treated has received at least 3-5 prior therapies for MM (claims 3-6 of ‘965 and instant claims 70 and 76). The patent and instant application further claim wherein the prior therapies include an anti-CD38 antibody, a proteasome inhibitor and in an immunomodulatory drug (instant claim 70 and claims 7-13 of ‘965). The patent and instant application claim that the subject has a MM immune subtype of immunoglobulin (Ig) G, Ig A, lamda or kappa light chain or an extramedullary plasmacytoma (claims 14-15 of ‘965 and instant claim 75). Both the patent and instant application claim wherein the bispecific antibody is administered in a dosing regimen wherein the initial dose, administered during the first week, is less than the subsequent second dose, which is itself less than the subsequent third dose (claim 1 of ‘965 and instant claim 70). The ‘965 patent does not claim wherein each of the second and third doses are administered respectively during the second and third weeks of the dosing regimen or wherein each of the first-third doses is split into two fractions administered on consecutive days.
Chu teaches administration of a bispecific antibody binding CD20 and CD3 for the treatment of a B cell proliferative disease, including multiple myeloma (e.g., col. 31, line 60, through col. 32, line 36). It is taught in col. 2, lines 17-19, that the bispecific antibody administration may comprise three doses, with the first (C1D1) being less than the second (C1D2), which is less than the third (C1D3): “In some embodiments, the C1D2 is greater than the C1D1 by about 50% to about 250%. In some embodiments, the C1D3 is greater than the C1D2 by about 150% to about 300%.” (see also col. 2, lines 20-31, and col. 2, lines 17-19) The administration may be weekly (col. 3, lines 27-31). The bispecific antibody may be administered over a series of treatments (col. 33, lines 38-40). It is further taught that doses may be fractionated to reduce or inhibit unwanted treatment effects, such as cytokine release syndrome (CRS) or infusion-related reactions (col. 19, lines 50-64). Preclinical data with the anti-CD20/anti-CD3 bispecific antibody indicated that fractionation might decrease the risk of cytokine-driven toxicities (col. 52, lines 35-38).
It would have been obvious wherein administration of the first, second and third doses were during weeks 1-3, respectively, since Chu taught that regimen for treatment of a B cell proliferative disease, e.g. multiple myeloma. Additionally, it would have been obvious to have split each dose into two administrations (fractions) to reduce the potential for CRS or infusion-related reactions as suggested by Chu.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WIPO documents WO 2014/140248 A1, WO 2016/166629 A1, WO 2017/031104 and W0 2018/083204 (all cited in the IDS filed 11/6/2024) were cited in the previous Office action (Prior Art) as disclosing anti-BCMA or anti-CD3 bispecific antibody cancer treatment, including of multiple myeloma, but there is no disclosure of or suggestion to administer at least 3 increasing doses of the bispecific antibody.
ClinicalTrial.gov study NCT03933735, ver.1 (https://clinicaltrials.gov/study/NCT03933735?term=tnb-383b&rank=1&tab=
history&a=1#version-content-panel, 04/29/2019) was cited in the previous Office action (Prior Art) as teaching treatment of refractory MM with a bsAb that binds CD3 and BCMA; although, the bsAb does not have the CDRs of the HVCRs and LVCR of the instant claims. As further described by D’Souza et al. (J. Clin. Oncol. 40(31):3576–3586, 27 Aug. 2022), published after the effective filing date of the instant application, ClinicalTrial study NCT03933735 used 21-day (every 3 weeks) dosing cycles of TNB-383B, later known as ABBV-383. There was no step-dosing. (p. 3578, col. 1, first full paragraph, and p. 3577, col. 1, start of second paragraph). It mentions instant REGN5458 bsAb (p. 3584, col. 1, second paragraph). D’Souza et al. conclude (p. 3584, col. 2, second paragraph), “ABBV-383 doses of 60 mg once every 3 weeks as well as 40 mg once every 3 weeks have been selected for further dose exploration and optimal-dose selection. The safety and efficacy of ABBV-383 will be investigated further in this ongoing phase I study.” This study does not make obvious administration of at least three increasing doses administered to the same patient.
Jaki et al. (Canc. Chemo. Pharm. 71:1107-1114, 2013) describes principles of dose-finding studies. The most common method, used in about 97% of studies, is the “3+3” dose-escalation design (p. 1108, last paragraph, and, e.g., Fig. 2), which uses distinct patient cohorts given different doses. That is, each cohort receives one dose, which may be administered multiple times. Jaki et al. is cited to show the state of the art.
Allowable Subject Matter
Claims 77-83 and 87-89 are allowed.
Conclusion
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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Claire Kaufman
/CLAIRE KAUFMAN/Primary Examiner, Art Unit 1674
February 23, 2026