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 .
Election/Restrictions
In response to the restriction requirement dated 02 February, 2026, Applicant elects, without
traverse, SEQ ID NO: 70: DVSSYLEEQAVREFIEWLVRGGPSSGAPPPSK[C16]-NH2 wherein K[C16] represents a lysine acylated at its side chain amino group with a C16 diacid to form a side chain structure of (C4 alkyl)NH-CO(CH₂)14COOH. Claims 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35 read on the elected species. Applicant’s election in the reply filed on 27 April 2026 is acknowledged.
Claims 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35 are hereby examined on the merits. Claims 7, 12, 24, 27-29 and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim status
Claims 1-3, 7-9, 12, 14, 17, 19-20, 23-24, 26-29, 32, 34 and 35 are pending. Claims 2, 3, 7, 8, 9, 12, 14, 17, 19, 20, 23, 24, 26 and 27 are currently amended. Claims 4-6, 10-11, 13, 15-16, 18, 21-22, 25, 30-31 and 33 are cancelled. Claims 7, 12, 24, 27-29 and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Claims 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35 read on the elected species and are hereby examined on the merits.
Priority
This application filed 08/03/2023 is a National Stage entry of PCT/US2022/016406 , International Filing Date: 02/15/2022. PCT/US2022/016406 Claims Priority from Provisional Application 63149852 , filed 02/16/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/03/2023, 07/21/2025 and
01/21/2026 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure
statement is being considered by the examiner.
Claim Objections
Claim 9 is objected to because of the following informalities: Examiner respectfully requests a period at the end of the claim. Appropriate correction is required.
Claim 26 is objected to because of the following informalities: Examiner respectfully requests correcting “change” in line 4 to “chain”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35 are rejected under 35 U.S.C. 103 as being obvious over James T. Patterson et al., hereinafter Patterson (James T. Patterson et al., A Novel Human-Based Receptor Antagonist of Sustained Action Reveals Body Weight Control by Endogenous GLP-1, ACS Chem. Biol. 2011, 6, 135-145; published October 2010; reference provided in IDS) in view of Defelippis et al., hereinafter Defelippis (Defilippis et al., WO 03/020201A2; published 13 March 2003).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
For prior art purpose, Examiner interprets claims 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35, as being directed to the species elected by the Applicant.
Regarding claim 1, Patterson teaches GLP-1 receptor antagonist GLP-1/Ex-4 N-terminally truncated hybrid peptides (see Supplementary Table 1, peptide #41; Jant-4(9-40)a Lys40-C16). The hybrid peptide in Patterson, DVSSYLEEQAVREFIAWLVKGGPSSGAPPPSK-NH2, differs from the instant elected species at two amino acid residues which are underlined. Patterson teaches that Glu16, Val19 and Arg20 bestows superior potency relative to Ex-4 (9-39)a antagonism (Introduction, last paragraph). Patterson teaches that a triple substitution Glu16, Val19, Arg20 define minimal changes to yield a GLP-1 antagonist (see page 137, last paragraph) and confirm the seminal importance of Glu16, Val19 and Arg20 in achieving high potency antagonism. Glu16, Val19 and Arg20 are in bold font in the sequence in Patterson (noted above), and notably, these residues are preserved in the claimed peptide. Patterson teaches that Jant-4 antagonists acylated with palmitic acid (i.e. C16) improves potency by approximately 3-fold (see page 139, section ‘Fatty acid acylation enhances antagonism’; Fig 6). Synthesis of acylated analogs is achieved on resin at an additional C-terminal lysine position 40 (i.e. K[C16]) (page 139, section ‘Fatty acid acylation enhances antagonism’).
Patterson does not teach substituting the underlined amino acids ‘A’ and ‘K’ with the instant ‘E’ and ‘R’.
Defilippis teaches GLP-1/Extendin-4 peptide analogs (see page 17, last paragraph). A preferred group of GLP-1 analogs represented in Formula III (SEQ ID NO: 3) is a 100 % match to SEQ ID NO: 70 in the instant application. Defilippis teaches, that Xaa at position 30 (which corresponds to position 24 in Patterson) is Ala or Gly or Ser or Thr or…; Xaa at position 34 (which corresponds to position 28 in Patterson) is Lys or Arg or Glu or Asp or Asn or His (page 20, line 10). Defilippis teaches that it is preferred that the amino acid at position 30 (i.e. position 24 in Patterson) is substituted with glutamic acid (see page 23, last line). Defillippis discloses that a conservative substitution is a replacement of an amino acid with another that has the same net electronic charge and approximately the same size and shape (see page 16, first paragraph).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
One motivated to do so would have a reasonable expectation of success, as all references are
directed to GLP-1 peptide analogs. Patterson specifically teaches GLP-1 receptor antagonist Jant-4(9-40)a Lys40-C16. One would have recognized that applying the teachings in Patterson and substituting two amino acids with the teachings in Defilippis, would yield predictable results and generate a repertoire of peptide antagonists, as Defillippis discloses that a conservative substitution is a replacement of an amino acid with another that has the same net electronic charge and approximately the same size and shape (see page 16, first paragraph) and additionally, as noted, are not the amino acids involved in preserving or potentiating antagonism (see page 137, last paragraph). See MPEP § 2143 I(A)(B); MPEP § 2144.05 II(A).
Regarding claims 2, 3 and 8, 14, 17, 19 the obviousness rationale has been set forth above in the teachings of Patterson and Defilippis.
Regarding claim 9, the teachings of Patterson and Defilippis have been set forth above. Patterson teaches that Jant-4 antagonists acylated with palmitic acid are synthesized with the objective of extending serum half-life by facilitating binding to albumin. Acylated peptide binding to albumin is detected by a plasma shift assay (Supplementary Figure 8). Further examination of C8, C14, and C18 fatty acids show similar improvements in potency (see page 139, first paragraph).
Regarding claim 26, the obviousness rationale has been set forth in the teachings of Patterson, and Defilippis. Patterson teaches X40 is an acetylated lysine with a C16 acyl group, R20 is amidated (i.e. CONH2) and Lys40-C16 antagonists are acylated on the side-chain. (see legend for Supplementary Table 1). Patterson teaches that Jant-4 antagonists acylated with palmitic acid are synthesized with the objective of extending serum half-life by facilitating binding to albumin. Acylated peptide binding to albumin is detected by a plasma shift assay (Supplementary Figure 8).
Regarding claim 34, Patterson teaches PBS (Supplementary methods, CD).
Regarding claim 35, embodiments of the specification disclose “treating” wherein “said method comprises the step of administering to a patient in need thereof” (page 52 of specification, lines 21-23; page 2 lines 5-6). Patterson teaches that the humanization of Jant-4 relative to Ex-4 and the application of acylation to simplify chronic in vivo studies renders peptide #41 (i.e. Jant-4(9-40)a Lys40-C16) a preferred choice for human studies (see page 141, first paragraph last few lines). Patterson discloses the use of this long-acting peptide as a subcutaneous injection to persistently antagonize endogenous GLP-1 in metabolically compromised obese mice (i.e. atypical hypoglycemia; i.e. patient). Patterson teaches a dose of 0.5 µmol kg-1 and blood glucose levels after administration of antagonist or vehicle (Fig 8b) (i.e. effective amount). Also see Fig 8 (page 142); Methods ‘one week in vivo study’ (page 143).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
One motivated to do so would have a reasonable expectation of success, as Patterson specifically teaches administering GLP-1 receptor antagonist Jant-4(9-40)a Lys40-C16. One would have recognized that administration can be performed in the peptide in Patterson, substituting two amino acids as suggested in Defilippis, to yield predictable results and generate a repertoire of peptide antagonists for administration to patients. See MPEP § 2143 I(A)(B); MPEP § 2144.05 II(A).
Claim 1, 2, 17, 20 and 23 are rejected under 35 U.S.C. 103 as being obvious over James T. Patterson et al., hereinafter Patterson (James T. Patterson et al., A Novel Human-Based Receptor Antagonist of Sustained Action Reveals Body Weight Control by Endogenous GLP-1, ACS Chem. Biol. 2011, 6, 135-145; published October 2010; reference provided in IDS) in view of Defelippis et al., hereinafter Defelippis (Defilippis et al., WO 03/020201A2; published 13 March 2003) further in view of Richard D. Dimarchi hereinafter Dimarchi (Richard D. Dimarchi et al., WO 2016/049190 A1; published 31 March 2016).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 20, the teachings of Patterson and Defilippis have been set forth above.
Patterson and Defilippis do not teach a spacer.
Dimarchi teaches incretin-insulin conjugate peptides which stimulate weight loss in an individual (see Abstract). The incretin component of the conjugate can be e.g. GLP-1 (see page 4, line 4). Dimarchi teaches incretin moiety acylated at the lysine amino acid side chain at position 40. In particular, the "U" of SEQ ID NO: 1927 represents a lysine acylated with a C16 acyl group via a gamma glutamic acid linker (Lys(y-5 Glu-C16)) (page 17, lines 2-5) (i.e. (ii) in the instant claim; covalently linked). Dimarchi teaches that in SEQ ID NO: 1931, X10 is Lys acylated with a C16 to C20 alkyl group optionally via a gamma Glu linker (page 47, line 16); In one embodiment a C12, C, 13, C14, C15, C16, Cl 7, C18, C19 or a C20 acyl or alkyl group 25 is linked to the side chain of an amino acid at position 10 or 40, optionally through a linker such as gamma glutamic acid (page 48, lines 24-26; page 159). Dimarchi teaches that using a C-peptide linker provides a novel structural location where many chemical modifications can be successfully deployed (page 3, lines 19-21). Additionally, Dimarchi teaches a spacer can be a dipeptide or tripeptide (i.e. (i) in the instant claim) consisting of naturally occurring and/or non-naturally occurring amino acids (see page 64, lines 20-28).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
One motivated to do so would have a reasonable expectation of success, as all references are
directed to GLP-1 peptide analogs. Patterson specifically teaches GLP-1 receptor antagonist Jant-4(9-40)a Lys40-C16. One would have recognized that applying the teachings in Patterson and Defilippis and introducing a spacer as suggested in Dimarchi, would provide a novel structural location where many chemical modifications can be successfully deployed (page 3, lines 19-21). See MPEP § 2143 I(A)(B); MPEP § 2144.05 II(A).
Regarding claim 23, the obviousness rationale has been set forth above in the teachings of Patterson, Defilippis and Dimarchi. Dimarchi, teaches spacer of the general structure of Formula II. Spacer is attached to any amino acid comprising a moiety which permits linkage to the spacer. For example, an amino acid comprising a side chain -NH2, -OH, or-COOH (e.g., Lys, Orn, Ser, Asp, or Glu) is suitable (page 64, lines 1-3). The spacer can comprise, for example, NH2(CH2CH2O)n(CH2)mCOOH, wherein m is any integer from 1 to 6 and n is any integer from 2 to 12 (page 64, lines 7-9).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 8, 9, 14, 17, 19, 20, 23, 26, 34 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-9, 14-21 of copending Application No. 18/365,081 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, reference application ‘081 teaches a GLP-1 receptor antagonist of SEQ ID NO: 97 which is a 100 % match to the instant sequence Seq ID NO: 70. Reference application ‘081 teaches fatty acid covalently linked to the N-terminal alpha amine of the antagonist (see claims 1-4, 7-9, 14-20). Reference application ‘081 teaches that the GLP-1 receptor antagonist further comprises a C-terminal extension of 1-3 amino acids wherein one of the amino acids is optionally an acylated Lysine (i.e. K[C16]) (see claim 6).
Regarding claims 2 and 3, reference application ‘081 teaches the GLP-1 receptor antagonist of SEQ ID NO: 97 (see claims 1-4, 7-9)
Regarding claim 8, reference application ‘081 teaches a spacer (see claim 16, 17, 18).
Regarding claim 9, reference application ‘081 teaches fatty acid C14-C20 or diacid (see claims 1-4, 7-9, 14-20).
Regarding claim 14, reference application ‘081 teaches the peptide antagonist (see claim 6).
Regarding claim 17, reference application ‘081 teaches acylated lysine (see claim 6).
Regarding claim 19, reference application ‘081 teaches acyl groups and spacer (see claim 16, 17, 18).
Regarding claims 20-24, reference application ‘081 teaches spacers (see claim 18).
Regarding claim 26, reference application ‘081 teaches the peptide antagonist (1-4, 7-9, 14-20).
Regarding claim 34, reference application ‘081 teaches pharmaceutical composition (see claim 20).
Regarding claim 35 reference application ‘081 teaches a method of treatment (see claim 21).
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 5712707430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARCHANA VARADARAJ/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights