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 .
Claims 1-132, 165, 169-170, 176, and 178 have been cancelled. Claims 185-202 have been newly introduced.
Applicant's arguments filed 6/24/2026 have been fully considered but they are not fully persuasive.
Specification
The substitute specification filed 6/24/2026 has NOT been entered.
The amendment to the substitute specification adding SEQ ID NOS: 612, 613, and 614 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: SEQ ID NOS: 612, 613, and 614 and changes to the references to SEQ ID NOS: 507 and 519.
The replacement sequence listing submitted 6/24/2026 is also considered to be new matter. This sequence listing contains new SEQ ID NOS: 612, 613, and 614.
Applicant’s 6/24/2026 response states that the sequence listing has been amended to include new SEQ ID NOS 612-614 and that support for inclusion of these sequences can be found in the specification, for example, at paragraphs [0115]- [0116], [0254], [0262], [0593], [0595] of the application as published, and originally filed claims 4, 6, 8, and 9, where the sequences are disclosed. This is not agreed with. At least page 85 of the marked copy of the substitute specification changes SEQ ID NO: 519 to SEQ ID NO: 614 and at least page 86 of the marked copy of the substitute specification changes SEQ ID NO: 519 to SEQ ID NO: 612. SEQ ID NO: 519 has stereoisomer notations (i.e. (S) notation) for amino acids 2, 5, 9, and 10. These are absent in new SEQ ID NOS: 612 and 614. SEQ ID NO: 612 contains a different structure at amino acid 9 (i.e. 2-amino-3-(4’-(4-(4-(25 amino…) as compared to SEQ ID NOS: 519 and 614.
It is noted that SEQ ID NO: 506 is the pentapeptide GSGLL. At least pages 39 and 41 of the marked copy of the substitute specification now reference new SEQ ID NO: 613 and SEQ ID NO: 506 rather than SEQ ID NOS: 506-507. The structure of SEQ ID NO: 507 and new SEQ ID NO: 613 do not correspond.
In addition, page 224 (paragraph [00312] of the marked copy of the substitute specification changes SEQ ID NO: 519 to SEQ ID NO: 614 whereas SEQ ID NO: 519 in paragraph [0313] is unchanged. This is inconsistent with pages 85-86.
In addition, pages 224-225 (paragraph [0314]) of the marked copy of the substitute specification changes SEQ ID NO: 507 to SEQ ID NO: 612 whereas SEQ ID NO: 507 in paragraph [0315] is unchanged. This is inconsistent with pages 39 and 41.
Applicant has not provided a clear and detailed explanation for these new sequences and the changes (or lack of changes) to the specification. None is apparent. In addition, applicant should have pointed to all places (pages and line numbers) in the substitute specification where changes were made given the length and complexity of the specification. The examiner cannot be sure the changes discussed above reflect all of the changes.
Applicant is required to cancel the new matter in the reply to this Office Action.
Election/Restrictions
Claim 133 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 182-184 (Groups III-V), directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 11/12/205 is hereby withdrawn. Group II, claim 141, was rejoined previously. See Office action mailed 3/24/2026. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Table A discloses the sequences (CDRs, VH, VL, HC, LC) for various anti-GLP1R antibodies. Each of these specific antibodies is free of the art. The prior art does not disclose or suggest antibodies having these sequences.
Claim 133 as amended recites CDRs from the HCVR/LCVR pairs:
SEQ ID NOS: 26/34 correspond to antibody REGN9268 (mAb 17). Antibodies REGN9268 (mAb 17) (see SEQ ID NOS: 42/44 in claim 140, part (a)) and REGN9267 (mAb 5) (see SEQ ID NOS: 142/144 in claim 140, part (f)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (1). Claim 172, part (a), recites the explicit VH/VL sequences for mAb17. Claim 173, part (a), recites the explicit HC/LC sequences for mAb17. Claim 173, part (f), recites the explicit HC/LC sequences for mAb5.
SEQ ID NOS: 46/54 correspond to antibody REGN 7990 (mAb3). Antibodies REGN7990 (mAb 3) (see SEQ ID NOS: 62/64 in claim 140, part (b)), REGN15869 (see SEQ ID NOS: 82/84 in claim 140, part (c)), REGN18121- (see SEQ ID NOS: 414/84 in claim 140, part (s)), REGN18123- (see SEQ ID NOS: 416/84 in claim 140, part (t)), and REGN7989 (mAb 11) (see SEQ ID NOS: 203/205 in claim 140, part (i)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (2). Claim 172, part (b), recites the explicit VH/VL sequences for mAb3. Claim 173, part (b), recites the explicit HC/LC sequences for mAb3. Claim 173, part (c), recites the explicit HC/LC sequences for REGN15869. Claim 173, part (i), recites the explicit HC/LC sequences for mAb11. Claim 173, part (s), recites the explicit HC/LC sequences for REGN18121- and claim 173, part (t), recites the explicit HC/LC sequences for REGN18123-.
SEQ ID NOS: 86/94 correspond to antibody REGN8070 (mAb16). Antibodies REGN8070 (mAb 16) (see SEQ ID NOS: 102/104 in claim 140, part (d)) and REGN8069 (mAb 12) (see SEQ ID NOS: 223/225 in claim 140, part (j)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (3). Claim 172, part (c), recites the explicit VH/VL sequences for mAb16. Claim 173, part (d), recites the explicit HC/LC sequences for mAb16. Claim 173, part (j), recites the explicit HC/LC sequences for mAb12.
SEQ ID NOS: 106/114 correspond to antibody REGN 8072 (mAb4). Antibodies REGN8072 (mAb 4) (see SEQ ID NOS: 122/124 in claim 140, part (e)) and REGN8071 (mAb 13) (see SEQ ID NOS: 243/245 in claim 140, part (k)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (4). Claim 173, part (e), recites the explicit HC/LC sequences for mAb4. Claim 173, part (k), recites the explicit HC/LC sequences for mAb13.
SEQ ID NOS: 146/154 correspond to antibody REGN7988(mAb15). Antibodies REGN7988 (mAb 15) (see SEQ ID NOS: 162/164 in claim 140, part (g)) and REGN7987 (mAb 14) (see SEQ ID NOS: 331/333 in claim 140, part (n)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (5). Claim 172, part (e), recites the explicit VH/VL sequences for mAb15. Claim 173, part (g), recites the explicit HC/LC sequences for mAb15. Claim 173, part (o), recites the explicit HC/LC sequences for mAb14.
SEQ ID NOS: 166/174 correspond to antibody REGN5619 (mAb 2). Antibodies REGN5619 (mAb 2) (see SEQ ID NOS: 182/184 in claim 140, part (h)) and REGN9426 (mAb 6) (see SEQ ID NOS: 263/265 in claim 140, part (l)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (6). Claim 172, part (f), recites the explicit VH/VL sequences for mAb2. Claim 173, part (h), recites the explicit HC/LC sequences for mAb2. Claim 173, part (l), recites the explicit HC/LC sequences for mAb6.
SEQ ID NOS: 275/283 correspond to REGN5617 (mAb9). Antibody REGN5617 (mAb9) (see SEQ ID NOS: 291/293 in claim 140, part (m)) has a unique set of HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (7). Claim 172, part (g), recites the explicit VH/VL sequences for mAb9. Claim 173, part (m), recites the explicit HC/LC sequences for mAb9.
SEQ ID NOS: 335/343 correspond to antibody REGN9270 (mAb18). Antibodies REGN9270 (mAb 18) (see SEQ ID NOS: 331/333 in claim 140, part (o)) and REGN9278 (mAb 19) (see SEQ ID NOS: 371/373 in claim 140, part (p)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (8). Claim 172, part (h), recites the explicit VH/VL sequences for mAb18. Claim 173, part (n), recites the explicit HC/LC sequences for mAb18. Claim 173, part (p), recites the explicit HC/LC sequences for mAb19.
SEQ ID NOS: 375/383 correspond to antibody REGN9279 (mAb20). Antibodies REGN9279 (mAb 20) (see SEQ ID NOS: 391/393 in claim 140, part (q)) and REGN9280 (mAb 21) (see SEQ ID NOS: 411/413 in claim 140, part (r)) have the same HCDRs and LCDRs. These CDRs are recited explicitly in claim 171, part (9). Claim 172, part (i), recites the explicit VH/VL sequences for mAb20. Claim 173, part (q), recites the explicit HC/LC sequences for mAb20. Claim 173, part (r), recites the explicit HC/LC sequences for mAb21.
The light chains of SEQ ID NO: 44, 64, 84, 104, 124, 164, 184, 269; 273; 293; 313; 373; and 413 have the Q-tag of SEQ ID NO: 18 (LLQGSG) as amino acids 1-6.
The heavy chains of SEQ ID NO: 142, 203, 223, 243, 263, 267, 331, 351, and 391 have the Q-tag of SEQ ID NO: 18 (LLQGSG) as amino acids 1-6.
Independent claim 133 and dependent claims 134-135, 142-164, 166-168, 172-173, 175, 177, 179, 181, 185-191 are allowable.
Independent claim 141 and dependent claims 193-202 are allowable.
Claim Objections
Claim 171 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 133. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 171 depends upon claim 133. The CDRs of claim 133 are recited explicitly in claim 171; however, the scope of the claims does not differ.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 136-139, 140, 174, 180, and 192 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Independent claim 136 has been amended to remove SEQ ID NO: 519 and now references SEQ ID NO: 614. Dependent claim 137 references SEQ ID NO: 519. These claims contain new matter for the reasons set forth with respect to SEQ ID NOS: 507, 519, and 614 as set forth above. The structures and references to sequence identifiers are inconsistent throughout the specification, claims, and sequence listing.
Independent claim 138 has been amended to remove SEQ ID NO: 507 and now references SEQ ID NO: 612. Dependent claim 139 references SEQ ID NO: 507. Claim 174 depends upon claim 138 and references SEQ ID NO: 507. These claims contain new matter for the reasons set forth with respect to SEQ ID NOS: 507, 519, and 612 as set forth above. The structures and references to sequence identifiers are inconsistent throughout the specification, claims, and sequence listing.
Claim 140 depends from claim 133. The claim has been amended to remove SEQ ID NOS: 506-507 and to refer to SEQ ID NOS: 506 and 613. This claim contains new matter for the reasons set forth with respect to SEQ ID NOS: 507 and 613 as set forth above. The structures and references to sequence identifiers are inconsistent throughout the specification, claims, and sequence listing.
Applicant is reminded that each identical structure should be referenced by the same sequence identifier throughout the specification and claims. The sequence in the sequence listing should match the structure in the specification and claims.
Claim 180 was amended to recite “the antibody-tethered drug conjugate is present in an amount of about 5 mg to about 100 mg in the pharmaceutical dosage form.” Applicant pointed to basis in paragraph [0685]. This is not agreed with. This paragraph disclosed these amounts with respect to the antibody and not the antibody-tethered conjugate.
Claim 184 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 184 is dependent upon claim 133. Claim 184 is directed to a method of producing the antibody-tethered drug conjugate or a pharmaceutically acceptable salt thereof. The method as written is not enabled. There are no steps for producing the pharmaceutically acceptable salt. In addition, claim 133 has no limitations to the BA comprising at least m glutamine residues. Note that only the CDRs of the named sequences are required in claim 133. The steps of “contacting, in the presence of a transglutaminase” in claim 184, step (a), is insufficient to produce the compound of Formula (A). The method is incomplete and missing critical steps. See at least Example 7 (starting at page 509 of PGPUB20230330254).
Claim 183 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for method of enhancing GLP1R activity, lowering blood glucose levels, and lowering body weight, does not reasonably provide enablement for treating allGLP1R-associated conditions in a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The specification does not specifically define “treatment” and claim 183 does not provide a specific therapeutic effect to be achieved by “treatment.” Treatment is considered to include ameliorating all symptoms and aspects of GLP1R-associated conditions. In the absence of a specific therapeutic effect in the claim, all aspects of treatment must be enabled. Note that GLP1R-associated conditions are not defined by the specification although many examples are given. See at least page 246 at paragraphs [0691-0695] of PGPUB 20230330254. These conditions include Alzheimer’s Disease, cirrhosis, and myocardial infarction. At least for example, there is no evidence of record nor reason to believe that administration of the claimed antibody-tethered drug conjugate of claim 133 would ameliorate/reverse memory loss caused by Alzheimer’s Disease, reverse liver fibrosis/damage in cirrhosis, and/or ameliorate/reverse cardiac tissue damage due to myocardial infarction.
The scope of the claims is not enabled.
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.
Claims 140 and 182-184 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.
Claim 140 is confusing in reciting “SEQ ID NOS: 506 and 613” where there is only one structure shown. The specification and claim do not explain and it is not obvious how this single structure is represented by two sequence identifiers. The claim is confusing.
Claim 140 also recites “optionally, wherein the heavy chain immunoglobulin does not comprise a C-terminal lysine or lysine and glycine in any of parts (a)-(b) and (d)-(r).” This is confusing. Each of the heavy chains in these subparts contain “GK” at the C-terminal. The claim should make clear that the C-terminal amino acid (K) deleted or the two C-terminal amino acids (GK) are being optionally deleted.
Claim 182 is indefinite in reciting a method of selectively targeting GLP1R on a surface of a cell, in the body of a subject or in vitro where the body of the claim administers to a subject. There are not in vitro method steps.
Claim 183 is indefinite in reciting GLP1R-associated condition. The term “GLP1R-associated” in claim 183 is a relative term which renders the claim indefinite. The term “GLP1R-associated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Examples of such conditions does not provide a limiting definition such that the metes and bounds of the claim can be ascertained.
Claim 184 is indefinite in being directed to a method of producing the antibody-tethered drug conjugate or a pharmaceutically acceptable salt thereof. There are no steps for producing the pharmaceutically acceptable salt. In addition, claim 133 has no limitations to the BA comprising at least m glutamine residues. Note that only the CDRs of the named sequences are required in claim 133. The steps of “contacting, in the presence of a transglutaminase” in step (a) is insufficient to produce the compound of Formula (A). The method is incomplete and missing critical steps. See at least Example 7 (starting at page 509 of PGPUB2023/0330254).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
mpa
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