Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submissions filed on 9/15/2025 and 10/2/2025, have been entered.
Status of the Claims
2. Claims 1-31 are the original claims filed on 5/8/2020. In the Preliminary Amendment of 8/20/2020, Claims 1-37 are amended. In the second Preliminary Amendment of 9/22/2020, Claim 30 is amended. In the Response of 4/10/2023, Claims 1-4, 6-9, 11, and 27-31 are amended, claims 12-14 are canceled and new claims 32-37 are added. In the Response of 8/25/2023, Claims 1, 6, 10, 31, 34-35, and 37 are amended. In the Response of 2/8/2024, Claims 1 and 6 are amended. In the Response of 10/8/2024, Claims 1, 3-4, 11, 17-18, 21, 24-26, 28-31, and 36-37 are amended, claims 15, 19-20, and 22-23 are canceled, and new claim 38 is added. In the Response of 2/26/2025, Claims 1, 18, 21, 24 and 25 are amended and new Claim 39 is added. In the Response After Final Action of 7/14/2025, no claims are amended or added. In the RCE of 9/15/2025 and 10/2/2025 no claims no claims are amended, canceled or added.
Claims 1-11, 17-18, 21 and 24-39 are all the claims.
This Office Action contains new grounds for objection and rejection.
Priority
3. USAN 16/869,793, filed 05/08/2020, and having 3 RCE-type filing therein,
claims foreign priority to EP19208417.6, filed 11/11/2019.
Information Disclosure Statement
4. As of 12/3/2025, a total of five (5) IDS are filed for this application: 8/11/2020; 12/1/2021; 9/26/2022; 1/16/2025; and 6/9/2025. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Rejections
Double Patenting
5. The rejection of Claims 1-11, 17-18, 21 and 24-39 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10752694 in view of Cong et al (PTO 892 form)) is withdrawn.
Applicants allege neither claims 1-14 of the ‘694 patent nor Cong disclose or suggest administering the claim-recited antibody construct in one cycle comprising three individual administrations of a dose of the antibody construct, wherein one administration of the antibody construct is administered to the subject in a single day and other administrations of the cycle are administered on different days. Further both the ‘694 patent claims and Cong are silent with respect to therapeutically treating or ameliorating a B-cell maturation antigen (BCMA)- positive B cell neoplasm or a BCMA-positive plasma cell neoplasm in a human subject in need thereof. Said another way, claim 1 of the ‘694 patent is a product claim and does not recite (1) any dosing regimen, yet more importantly the dosing regimen recited in claim 1; and (2) the treating or ameliorating of a B-cell maturation antigen (BCMA)-positive B cell neoplasm or a BCMA-positive plasma cell neoplasm. Cong’s disclosure of PEGylation at histidine tags does not provide the elements of the instantly claimed method which are missing from the claims of the ‘694 patent.
6. The rejection Claims 1-11, 17-18, 21 and 24-39 on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 10766969 or claims of 28, 36-44, 47-52 of 17/011,849 (reference no. US 20220064336; U.S. Patent No. 12281175) or claims 2-5, 8-9 and 11 of 17/336,152 (reference no. US 20220356268; U.S. Patent No. 12281176) or claims 1-15 of U.S. Patent No. 9598500 or claims 1-15 of U.S. Patent No. 9150664 or claims 1-15 U.S. Patent No. 9340621 in view of Cong et al (PTO 892 form)) is withdrawn.
Applicants allege the claims of each of these cited patents are deficient in teaching the elements of the instant claims because they do not recite (1) the dosing regimen recited in claim 1; and (2) the treating or ameliorating of a B-cell maturation antigen (BCMA)-positive B cell neoplasm or a BCMA-positive plasma cell neoplasm. Cong's disclosure of PEGylation at histidine tags does not provide the elements of the instant claims which are missing from the claims of the '969 patent, the '175 patent, the '176 patent, the '500 patent, the '664 patent, or the '621 patent.
Rejections Maintained
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.
7. The rejection of Claims 1-11, 17-18, 21 and 24-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11352433 or claims 1-19 of U.S. Patent No. 10301391 in view of Cong et al (PTO 892 form)) is maintained.
Applicants allege none of the claims of the ‘433 or the ‘391 patent recite (1) any dosing regimen, yet more importantly the dosing regimen recited in claim 1; and (2) the treating or ameliorating of a B-cell maturation antigen (BCMA)-positive B cell neoplasm or a BCMA-positive plasma cell neoplasm. Cong’s disclosure of PEGylation at histidine tags does not provide the elements of the instantly claimed method which are missing from the claims of the ‘433 patent and the ‘391 patent.
Response to Arguments
A) Contrary to Applicant’s assertion under (2) herein above, the reference patents claim the treating or ameliorating of a B-cell maturation antigen (BCMA)-positive B cell neoplasm or a BCMA-positive plasma cell neoplasm:
Ref ‘433
18. A method of treating or ameliorating a B cell disorder correlating with B cell maturation antigen (BCMA) overexpression, a plasma cell disorder, or an autoimmune disease, comprising the step of administering to a subject in need thereof the antibody construct of claim 1.
Ref ‘391
17. A method of treating or ameliorating a B cell disorder correlating with B cell maturation agent (BCMA) overexpression, a plasma cell disorder, or an autoimmune disease comprising the step of administering to a subject in need thereof an effective amount of the antibody construct of claim 1.
B) As regards Applicants allegation under (1) herein above that none of the claims of the ‘433 or the ‘391 patent recite any dosing regimen, yet more importantly the dosing regimen recited in claim 1, it is permissible to consult the ref specification on the scope and meaning of a method of treatment claim under Sun Pharmaceuticals.
That the portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. See MPEP 804 II(B)(1) stating in part:
The court in Vogel recognized “that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,” but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first “determine how much of the patent disclosure pertains to the invention claimed in the patent” because only “[t]his portion of the specification supports the patent claims and may be considered.” The court pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. V. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
To avoid improperly treating what is disclosed in a reference patent or copending application as if it were prior art in the context of a nonstatutory double patenting analysis, the examiner must first properly construe the scope of the reference claims. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. If claims to the compound’s use and the compound were subject to a restriction requirement, and the compound was elected, a nonstatutory double patenting rejection may not be appropriate in a divisional application claiming the restricted compound’s use. See MPEP § 804.01. However, subject matter disclosed in the reference patent or application that does not fall within the scope of a reference claim cannot be used to support a nonstatutory double patenting rejection as this would effectively be treating the reference patent or application as prior art.
A half-life extending moiety comprising the instant claimed BiTE is broadly taught in the ref specifications:
FIG. 6: Mean PK profiles of nine different BiTE® antibody constructs, each fused to an scFc half-life extending moiety. For reasons of comparability, serum concentrations were dose-normalized to 15 μg/kg and indicated in nmol.
Dosing regimen is broadly taught in the ref specifications:
The compositions of the present invention can be administered to the subject at a suitable dose which can be determined e.g. by dose escalating studies by administration of increasing doses of the antibody construct of the invention exhibiting cross-species specificity described herein to non-chimpanzee primates, for instance macaques.
These drugs may be administered simultaneously with the composition comprising the antibody construct of the invention as defined herein or separately before or after administration of said antibody construct in timely defined intervals and doses.
Dosing that falls within the instant claim scope (at least 800 ug) is taught:
A typical dosage may range from about 0.1 pg/kg to up to about 30 mg/kg or more, depending on the factors mentioned above. In specific embodiments, the dosage may range from 1.0 pg/kg up to about 20 mg/kg, optionally from 10 pg/kg up to about 10 mg/kg or from 100 pg/kg up to about 5 mg/kg.
The respective claim sets are drawn to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. The ref claim 21 shares the anti BCMA VH/VL CDR1-3 of instant Claim 1, element (i) for SEQ ID NOs: 71-73 (VH) and 75-77 (VL):- VL element (1): SEQ ID NO:48 NHIIH; SEQ ID NO:49 YINPYPGYHAYNEKFQG; SEQ ID NO:50 DGYYRDTDVLDY; and VH element (i) SEQ ID NO:45 QASQDISNYLN; SEQ ID NO: 44 YTSRLHT; SEQ ID NO: 45 QQGNTLPWT.
10. The antibody construct of claim 1, comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 55, 56, 61, 62, 73, 74, 79, 80, 91, 92, 97 and 98.
The polypeptide of SEQ ID NO: 180 for instant Claim 26 comprises the antibody construct of instant method claim 1 and shares 99.9% similarity with the antibody construct of the ref patent sequences of SEQ ID NOS: 61 and 62:
Ref SEQ ID NO: 61:
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Ref SEQ ID NO: 62
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The ref patents teach there is a need in the art for bispecific therapeutics that retain similar therapeutic efficacy, that have a format which is straightforward to produce, and that have favorable pharmacokinetic properties, including a longer half-life. The ref patents teach additional domains (or a third domain) comprising a tag which is e.g. helpful in the isolation of the molecule or relate to an adapted pharmacokinetic profile of the molecule and include PEG molecules. Instant claim 1 requires a third domain that extends the serum/plasma half-life. It is known in the art that strategies to extend serum half-life from a His-tagged protein includes PEGylation (Cong et al). Accordingly, extended half-lives of recombinant proteins is well known in the art.
The ref patents teach the compositions can be administered to the subject at a suitable dose which can be determined e.g. by dose escalating studies by administration of increasing doses of the antibody construct of the invention. The ref patents teach dose ranges for the AMG 701 antibody construct being “A typical dosage may range from about 0.1 μg/kg to up to about 30 mg/kg or more, depending on the factors mentioned above. In specific embodiments, the dosage may range from 1.0 μg/kg up to about 20 mg/kg, optionally from 10 μg/kg up to about 10 mg/kg or from 100 μg/kg up to about 5 mg/kg.”
The ref patents teach frequency of administration where the antibody construct of the invention will generally be designed for specific routes and methods of administration, for specific dosages and frequencies of administration, for specific treatments of specific diseases, with ranges of bio-availability and persistence, among other things. The materials of the composition are preferably formulated in concentrations that are acceptable for the site of administration.
Under MPEP 2144.05 In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
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. “[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). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960) (MPEP 716.02(d)).
The subject matter disclosed in the reference patents falls within the scope of the broadly drawn reference claims 18 and 17, respectively. The dosing regimen recited in instant claim 1 or the dependent claims is not shown to be more effective, surprising, unexpected or critical over the broad method invention of the ref patents.
The rejection is maintained.
New Grounds for Objections
Claim Objections
8. Claims 4 and 32 are objected to because of the following informalities:
a) Claim 4 recites 800 ug/day and 12 mg per day. Amend claim 4 to recite “12 mg/day” to comport with the claim set.
b) Claim 32 recites “12 mg per day.” Amend claim 32 to recite “12 mg/day” to comport with the claim set.
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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.
9. Claims 1-5, 7-11, 17-18, 21 and 24-39 are 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.
a) 1-5, 7-11, 17-18, 21 and 24-39 are unclear and indefinite for the recitation in claim 1:
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. It is not ascertainable whether the penultimate “wherein” clause is or is not related to the final “wherein” clause.
If the two “wherein” clauses are intended to be related, then amend claim 1 to recite “wherein the one cycle comprising at least three administrations comprises a first administration of the antibody construct day, and a second and a third administration of the antibody construct on different days.”
See claim 6 for clarity and that is not rejected.
Conclusion
10. No claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643