DETAILED ACTION
Examiner acknowledges receipt of the reply filed 8/3/2026, in response to the restriction requirement mailed 6/05/2026.
Claims 1-30 are pending. Claims 9-14 and 17-30 are withdrawn from further prosecution for the reasons set forth below.
Claims 1-8, 15, and 16 are being examined on the merits in this office action.
This is a Track One application.
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 .
Priority
The filing receipt dated 6/03/2026 provides the following information:
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Election/Restrictions
Applicant’s election of Group I (claims1-16) in the reply filed on 8/03/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 17-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/03/2026.
Applicant’s election of the following species in the reply filed on 8/03/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Z1 moiety: SEQ ID NO:22
Z2 moiety: SEQ ID NO:2
Peptide linker: AG
Tri-agonist: SEQ ID NO:252
Claims 1-8, 15, and 16 read on the elected species.
Claims 9-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/03/2026.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The abstract of the disclosure is objected to for the following minor informality:
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Here, the abstract recites: “The present invention relates to” and “The invention also relates to” at lines 1 and 3, respectively.
Claim Objections
Claims 1 and 2 are objected to because of the following informalities:
Regarding claim 1, the acronyms GLP-1 and GIP should be written out in full name in the first appearance in the claims.
Claim 1 should further be amended to recite:
X₃₀ represents Gly (G), or Ala (A),
X₃₁ represents Pro (P), Gly (G), or Ala (A),
X33 represents Ser (S), and
X68 represents Glu (E), [[or]] Lys (K), or (Gln (Q), and
Claim 2 should be amended to recite:
X43 ... or is absent
X44 ... or is absent
X₄₅ represents Glu (E), Gly (G), Pro (P) or is absent,[[\]]
X₄₉ represents Glu (E), Pro (P) or is absent, and
Appropriate correction is required.
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 1, 5-7, and 16 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.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP § 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP § 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, the claims are drawn to a GLP-1-/GIP-/amylin-receptor tri-agonist comprising Z1-L1-Z2 wherein Z1 comprises SEQ ID NO:161, L1 is a peptide linker, and Z2 comprises SEQ ID NO:164.
The specification does not explicitly define the term “peptide linker”. Claim 2 recites a peptide linker formula. Claim 3 recites the peptide linker AG.
The peptide linker can be of any to length, charge, or secondary/tertiary structure. There is limited guidance as to peptide linkers that can function as a linker between Z1 and Z2 moieties and further maintain structure and functional interaction by the Z1/Z2 moieties with the GLP1/GIP/amylin receptors.
Claim 5 recites that the tri-agonist further comprises a “protraction moiety”. Claim 7 recites that the “protraction moiety” comprises a linker. The linker within the “protraction moiety” is not expressly defined.
The PGPUB of the instant specification states at paras [0379]-[0380]:
The term “protraction moiety” as used herein refers to a moiety having half-life extending properties and comprising a “protractor P” and an optional “linker Lp”, and may be represented by the general formula “Lp-P”, in which Lp is said optional linker and P is said protractor.
The term “protractor” as used herein refers to a molecule which is capable of increasing the plasma half-life of the peptide to which it is attached. The term “protraction” thus refers to half-life extension and the terms “protractor”, “protraction moiety” or “half-life extending moiety” thus serve the purpose of extending the plasma half-life of the peptides as disclosed herein.
Claim 8 recites two protraction moiety structures. The specification provides limited guidance as to compounds that can be construed as “half-life extending moieties”.
The issue at question is whether a person of ordinary skilled in the art would be able to determine what structural features are required for the instant claimed peptide linkers, protraction moieties, and linkers therein that can form the claimed tri-agonist and maintain overall functional utility in GLP-1-/GIP-/amylin-receptor agonism.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
The specification is limited to peptide linkers and protraction moieties that were reduced to practice, e.g. claims 4, 8, and 15.
Example 1 discloses reference compounds 1-7. Example 2 discloses compounds 104-197, and 211-221. Example 3 discloses LCMS results of specific peptides. Example 4 discloses GLP1-, GIP- and amylin receptor binding assay results of reference compounds 1-7 without and with HSA (Tables 11 and 13) and compounds 104-197, 211-221 without and with HSA (Tables 12 and 14). Example 5 discloses that the peptides reduced food intake/ suppressed appetite. Example 6 discloses pharmacokinetic results (Table 16). Example 7 discloses chemical stability results of peptide formulations (Table 17).
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure:
As discussed above, in the instant case, based on the disclosure of instant specification, other than the limited examples, a person of ordinary skilled in the art would not be able to determine what structural feature is required for the claimed peptide linker to maintain functional activity of the Z1 and Z2 moieties for GLP-1, GIP, and amylin receptor agonism. The same holds true for the claimed protraction moiety.
Furthermore, the present application is attempting to patent what has not yet been invented and the fact that one of skill in the art can test for the effect used to determine the compounds does not necessarily confer sufficient written description. The claimed tri-agonist peptides would entail testing limitless potential peptides and proteins, and one of skill in the art could afterwards still be faced with no hits with the desired functionality.
In addition, it is well known in the peptide/protein art that even single amino acid changes or differences in the amino acid sequence of a protein can have dramatic effects on the protein’s function. As an example of the unpredictable effects of mutations on protein function, Drumm et al (Annu. Rev. Pathol. Mech. Dis., 2012, 7, pages 267-282) teach cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, for example, page 268, Section “CYSTIC FIBROSIS”. Drumm et al further teach several mutations can cause cystic fibrosis, including two mutations G551D and G551S; and clinical consequences are quite different for these two changes, as the G551D variant has virtually no detectable activity, and consequently a classic, severe phenotype is associated; G551S, however, has reduced but clearly detectable function and is associated with a much milder presentation of CF, for example page 269, left column, the last paragraph. Drumm et al also teach that in the most common cystic fibrosis mutation ΔF508 (the absence of amino acid 508 of the normally 1,480-amino acid protein) gives rise to the cystic fibrosis phenotype, for example, page 268, right column, the 2nd paragraph. Thus, even the substitution or deletion of a single amino acid can have dramatic and unpredictable effects on the function of the protein. The unpredictability of the effect of amino acid substitution on the function and/or property of peptide/protein is further confirmed and discussed in Yampolsky et al (Genetics, 2005, 170, pages 1459-1472). Yampolsky et al teach even conservative substitution can significantly affect the function of the protein/peptide, for example, page 1465, Table 3. Although the disclosures of Drumm et al and Yampolsky et al are directed to proteins/peptides other than the claimed tri-agonist peptides, they illustrate the inherent unpredictability with respect to the biological activity of a given protein/peptide after even minor changes to the primary amino acid sequence.
Therefore, based on the state of art, a person of ordinary skilled in the art would not be able to determine what structural feature is required for the claimed peptide linkers, further having the overall function of GLP-1-/GIP-/amylin-receptor agonism. The same is true for the protraction moieties. The skilled artisan cannot extrapolate to all iterations of peptide linkers, protraction moieties, and linkers therein that can be combined with Z1 and Z2 peptides, while maintaining the overall structure and functional utility of interacting with GLP-1-/GIP-/amylin-receptors.
(d) representative number of samples:
In the instant case, the genus of instant claimed peptide linkers, protraction moieties and linkers therein encompasses numerous compounds and combinations thereof. However, the specification is limited in setting forth compounds that fall within the claim scope and maintain overall structure and function in receptor agonism.
Considering the scope of the genus of instant claimed peptide linkers, protraction moieties and linkers therein, the instant specification fails to provide sufficient examples to describe the entire genus of peptide linkers, protraction moieties and linkers therein claimed.
Taken all these together, considering the state of the art and the disclosure in instant specification, it is deemed that the instant specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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.
Claim 8 is 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 8 recites the GLP-1-/GIP-/amylin-receptor tri-agonist according to 5, wherein the protraction moiety is … wherein R1 is the point of attachment of the protraction moiety to the epsilon amino group of the lysine in the peptide Z1 - L1 - Z2. Claim 1 recites only two amino acid positions that contain lysine: “X₁₂ represents Lys (K) or Ile (I)” and “X₆₈ represents Glu (E) or Lys (K), or Gln (Q)”. It is noted that lysine is not required to be present in the claimed GLP-1-/GIP-/amylin-receptor tri-agonist because the X12 and/or X68 position recite other/alternative amino acids that could be present in lieu of lysine.
Accordingly, claim 8 is not deemed to have antecedent basis from claim 1 because embodiments of the claimed tri-agonist may not comprise lysine, as required by claim 8.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 15 depends from claim 1.
Claim 1 recites:
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Per the sequence listing filed 12/01/2025, Z1 moiety of SEQ ID NO:168 has the following sequence:
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Z2 moiety of SEQ ID NO:165 has the following sequence:
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The peptide sequences of Z1-L1-Z2 do not allow for any modifications at any residue positions within the recited peptide.
In contrast, claim 15 recites:
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The peptide of claim 15 recites a side chain modification at lysine, position 12.
Accordingly, claim 15 is broader in scope than claim 1 because it recites a modification not provided for in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Relevant Art Not Relied Upon
Instant SEQ ID NO:168 has 90.7% identity with SEQ ID NO:45 of Wu et al (U.S. 2022/0168396).
Instant SEQ ID NO:165 has 95.9% identity with SEQ ID NO:79 of Kruse et al (U.S. 2023/0331803).
Instant SEQ ID NO:252 has 78.3% identity with SEQ ID NO:226 of Kruse et al (U.S. 2023/0331803).
Rondinone et al (WO 2023/288313- cited in IDS filed 12/01/2025) discloses multi-agonist peptides. Examples include the GLP1/GIP/amylin tri-agonist peptide of SEQ ID NO:16 (Example 1, compound no 16):
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However, the peptide does not correlate with the claimed formula of claim 1 (Z1-L1-X2, comprising SEQ ID NOs: 168 and 165).
Claims 2-4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Claims 1-30 are pending. Claims 9-14 and 17-30 are withdrawn.
Claims 1, 5-8, 15, and 16 are rejected. Claims 2-4 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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, LIANKO GARYU can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
