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 .
Claim Status
Claims 1-16 are pending.
Claims 12-16 are withdrawn as being directed to a non-elected invention, the election having been made on 1/8/2026. In response to species election, applicant elected the peptide SEQ ID NO: 40 conjugated with Lys(AEEAc-AEEAc-y-Glu-17-carboxyheptadecanoyl) at X9 position; thus, claims 2-5, 7-8, and 10 NOT reading on the elected species of SEQ ID NO: 40 conjugate are further withdrawn.
Claims 1, 6, 9, and 11 have been examined.
Priority
This application has PRO 63/435,723 12/28/2022
This application has PRO 63/389,769 07/15/2022
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/12/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objection
The objection to the specification is withdrawn because the amendments to the specification overcomes the objection of record.
The objection to claims 1 and 9 is withdrawn because the amendments to the claims overcome the objection of record.
The provisional rejection of claims 1, 6, 9, and 11 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/812,993 is withdrawn because claim 1 of 17/812,993 has been cancelled.
Maintained Rejection
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
1. Claims 1, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. (WO2006/086769 A2, cited in IDS) in view of Gabe et al. (Peptides. 2020 Mar:125:170224) and Mahalakshmi et al. (Methods Mol Biol. 2006:340:71-94).
Claim 1 is drawn to a peptide formula (I) or a pharmaceutically acceptable salt thereof.
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Levy et al. teach a GIP hybrid polypeptide comprising an N-terminal GIP analog fragment in combination with a C-terminal polypeptide having glucose lowering activity [0020]. Levy et al. teach the functional motifs of GIP hybrid polypeptide can be described as D-L-C-S defined as follows [00264].
Levy et al. teach the domain consisting of YA2EGTFI7SDYSIA13M14 [00293] and further teach alanine can be modified by 4-amino butyric amino acid (Aib) to resist DPP-IV at position 2 [0079, last line to 0080]. Levy et al. further teach substitutions of Met14 to Leu and His18 to Ala [0083, 00288]. Levy et al. further show substitution of Ile7 to Thr in various GIP analog polypeptide sequences [0084]. Levy et al. show a table for amino acid substitution of generating a GIP analog peptide comprising (i) Leu to ala (reading on Leu 21 to Ala), (ii) Leu to Ile (reading Leu 27 to Ile), and (iii) Asn to gln (reading on Asn 24 to Gln) [00330 and 00297-0029].
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Levy et al. did not specify further substitution of A13 to Aib.
Gabe et al. show GIP folded as a helical protein bound to the GIP receptor as follows (p3, Fig 3). Mahalakshmi et al. teach α-amino-isobutyric acid (Aib) and related Cαα dialkylated residues are strong promoters of helix formation (Summary). Mahalakshmi et al. teach centrally positioned Aib residues can promote formation of an incipient 310 helix by recruiting both the preceding and succeeding residues to the formation of a consecutive type III β-turn structure (p77, Sec 2.2. Helices). Because (i) Levy et al. teach ala can be substituted by Aib in a GIP analog peptide [00276], (ii) Gabe et al. show GIP forming a helical structure bound to its receptor and (iii) Mahalakshmi et al. teach centrally positioned Aib residues can promote formation of an incipient 310 helix, one of ordinary skill in the art would have found it obvious to beneficially substitute the centrally positioned A13 in Levy’s GIP to Aib. Levy et al. further teach a GIP hybridized to a peptide consisting of the following sequence of “KCNTATCVLGRLSQELHRLQTYPRTNTGSNTY” preferably in its C-terminal amide form [00238]. Levy et al. teach the amino acids the of last four amino acids at the C-terminus of GIP are X27= I, X28=A, and X29-30 as GG [00297-00299]. When, Levy’s GIP analog peptide compared to the claimed SEQ ID NO: 15 as follows shows the only difference is the linker sequence according the instant peptide formula (I). Levy et al. further teach a Trp-cage peptide sequence of PSSGAPPPS can be further added to the C-terminus of the modified GIP [0035] to link the second hormone peptide as follows, reading on the peptide SEQ ID NO: 15 (K* = lysine) in claims 1 and 9.
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With respect to claim 11, Levy et al. teach a pharmaceutical composition comprising the GIP hybrid polypeptide (e.g., SEQ ID NO: 15) and a pharmaceutically acceptable carrier [00353] such as buffer solution with salts [00473].
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Levy et al. with (ii) Gabe et al. in view of Mahalakshmi et al. because (a) Levy et al. teach a modified GIP hybrid peptide comprising Ala substituted by Aib [00276], (b) Gabe et al. show GIP forming a helical structure bound to its receptor (p3, Fig 3), and (c) Mahalakshmi et al. teach centrally positioned Aib residues can beneficially promote formation of an incipient 310 helix (p77, Sec 2.2. Helices). The combination would have reasonable expectation of success because centrally positioned Ala18 in GIP substituted by Aib is expected to promote helical protein structure as taught by Mahalakshmi et al.
Applicant’s Arguments
The claimed peptides that are multi-receptor agonists. Indeed, claimed peptides surprisingly exhibit tetra-receptor agonist activity and demonstrate potent functional activity at the GLP-1, GIP, Amylin and CT receptors as illustrated in Table 9 (SEQ ID NOs: 45, 47, 49-53, 55-57, and 59-61) in Remarks, (p30, para 2, Table 9 to p32, Table 12).
Levy et al contemplated using it as a peptide enhancer, to be appended at the end of the GIP sequence, and not as a linker (Remarks, p32 last para to p33, para 1-2).
Gabe broadly describes a postulated mechanism of activation upon peptide binding. Mahalaxsmi describes the utility of Aib incorporation for promoting helicity. Neither reference teaches: (a) which residue changes can be tolerated for receptor activation or (b) effects of lipidation on binding and activation, and both references are silent on the activation of GLP-1, amylin and calcitonin receptors (Remarks, p33, last para to p34., para 1-3).
Response to Arguments
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument (i) is not persuasive because the argument is not commensurate in scope of with the claims. The base claim is not limited to the peptide sequences in Table 9 and the rejected SEQ ID NO: 15 is not in Table 9.
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Applicant’s argument (ii) is not persuasive because applicant narrowly interprets Levy’s teachings. Levy et al. teach the selectable hybrid polypeptides of the invention may involve the use of chemically stable linkers to covalently attach the bio-active modules [0062]. Levy et al. further teach the Trp-Cage sequence of analog thereof is added the c-terminal of any GIP analog using a linker [0096].
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Applicant’s argument (iii) is not persuasive because the helical structure of GIP binding to GIP receptor was known in the art evidenced by Zhao et al. (eLife 2021;10:e68719). Zhao et al. show A13 of GIP (orange color) in a helical structure and localized to the hydrophobic binding pocket of GIP receptor as shown follows. Since both Ala and Aib are non-polar and hydrophobic amino acids as shown follows and Mahalakshmi et al. teach centrally positioned Aib residues can beneficially promote formation of an incipient 310 helix (p77, Sec 2.2. Helices), one of ordinary skill in the art would have found it obvious to beneficially substitute A13 in the hydrophobic binding pocket by Aib to promote formation of the helical structure. Furthermore, K* in the rejected SEQ ID NO: 15 is a lysine residue not a lipid conjugation as argued by applicant.
2. Claims 1, 6, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. in view of Gabe et al., Mahalakshmi et al. as applied to claims 1, 9, 11, and further in view of Musaimi et al. (2017 FDA PEPTIDE HARVEST, Spain, 2018)
Claim 6 is drawn to GIP hybrid peptide conjugated with fatty acid moiety at a lysine residue including the elected species of Lys(AEEAc-AEEAc-γ-Glu-17-carboxyheptadecanoyl).
Levy et al. teach the GIP hybrid peptide conjugated to fatty acid via a lysine residue [00303] and the GIP hybrid peptide consists of a single lysine residue corresponding to the X9 position of the peptide formula (I) as applied to claims 1, 9, and 11, but did not specify the conjugated lysine as Lys(AEEAc-AEEAc-γ-Glu-17-carboxyheptadecanoyl).
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Similarly, Musaimi et al. teach fatty acid conjugated to GLP-1 analog peptide via Glu residue linked to the Lys side-chain through the γ -carboxylic group to generate Semaglutide shown as follows (page 5). Because both Levy et al. and Musaimi et al. teach fatty acid conjugate to a lysine residue of a therapeutic peptide, one of ordinary skill in the art would have found it obvious to conjugate a fatty acid to Levy’s GIP hybrid peptide via Lys(AEEAc-AEEAc-γ-Glu-17-carboxyheptadecanoyl) as taught by Musaimi et al., reading on the elected conjugation species in claim 6.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Levy et al. in view of Gabe et al. and Mahalakshmi et al. with (ii) Musaimi et al. because (a) Levy et al. teach the GIP hybrid peptide conjugated to fatty acid via a lysine residue [00303], (b) Musaimi et al. show fatty acid conjugated to GLP-1 analog peptide via Glu residue linked to the Lys side-chain through the γ -carboxylic group for a therapeutic polypeptide (page 5). The combination would have reasonable expectation of success because both Levy et al. and Musaimi et al. teach conjugation of a fatty acid derivative to a lysine side chain of a peptide.
Response to Arguments
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive. See response to arguments above. In particular, arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See MPEP 2145(I). When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See 2121(I).
3. Claims 1, 6, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. in view of Gabe et al., Mahalakshmi et al., Musaimi et al. as applied to claims 1, 6, 9, 11, and further in view of Ryge et al. (US 2010/0048462 A1).
Claim 9 is drawn to the elected peptide sequence of SEQ ID NO: 40.
Levy et al. teach GIP analog peptide can be linked to a second hormone module/peptide via directly linked by the carboxy of a first module to the amino of a second module (reading on an amide bond). In addition, Levy et al. further teach any linking moiety can be used to attach the modules/peptides known in the art including PEG; amino acid, e.g., Lys, Glu, beta-Ala; polyaminoacids; bi-functional linkers, cleavable or non -cleavable linker. Levy et al. teach a glycine linker 1 to 30 residues in length [00217] or beta alanine linker [00337] in addition to a linker of PSSGAPPPS or its modified linker of PSSG [00305], consistent with this instant disclosure in the specification that the peptide domains in a GIP hybrid polypeptide can be connected either directly or via a linker [00245, 00274-PEG, 00863-Trp Cage, 00915-glycine or other peptide linker)]. Levy et al. teach the amino acids of the last four amino acids at the C-terminus of GIP of X27-30 are optional [00297-00299]. When X28=A and X29-30 = absent with a linker PSSG or GGGG, various Levy’s GIP hybrid polypeptide compared to the elected SEQ ID NO: 40 show the difference among the polypeptides is the linker/spacer sequence of GGPS as
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follows.
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Ryge et al. is cited to show conservative substitution of amino acids among Gly, Ser, and Pro with same physicochemical properties in a peptide known to one of ordinary skill in the art shown as follows [0075, Table 2].
Because (a) applicant admits GIP hybrid polypeptide can be connected either directly or via a linker in the specification [00245, 00274-PEG, 00863-Trp Cage, 00915-glycine or other peptide linker], consistent with Levy’s teaching described above, (b) Levy’s glycine linker or modified linker of PSSG are expected to connect the modified GIP* peptides in various length to the other hormone peptide to control plasma levels and/or treat various diseases/conditions taught by Levy et al. in the Abstract, and (c) Ryge et al. show conservative substitution of amino acids among Gly, Ser, and Pro with same physicochemical properties in a peptide known to one of ordinary skill in the art [0075, Table 2], one of ordinary kill in the art would recognize Levy’s GIP hybrid polypeptide comprising functionally equivalent peptide linkers (e.g., GGGG, PSSG) obvious to the instant linker of GGPS with the same physicochemical properties in the SEQ ID NO: 40. Thus, the elected peptide species of SEQ ID NO: 40 is further rejected by Levy et al. in view of Gabe et al., Mahalakshmi et al., Musaimi et al. and Ryge et al.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Levy et al. in view of Gabe et al., Mahalakshmi et al. and Musaimi et al. with (ii) Ryge’s conservative substitutions of amino acids for creating analog peptides because (a) Levy et al. in view of Gabe et al., Mahalakshmi et al. and Musaimi et al. teach a GIP hybrid with a poly glycine or a linker comprising a mixture amino acids of G, S, and P linker to connect the functional peptide domains and (b) Ryge et al. teach conservative substitutions among Gly, Ser, and Pro with same physicochemical properties for creating analog peptides.
Response to Arguments
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive. See response to arguments above.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 JIA-HAI LEE whose telephone number is (571)270-1691. The examiner can normally be reached Mon-Fri from 9:00 AM to 6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.L/Examiner, Art Unit 1658
28-July-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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