DETAILED ACTION
Examiner acknowledges receipt of applicant’s reply filed 11/17/2025, in response to the restriction requirement mailed 9/17/2025.
Claims 1-40 are pending.. Claims 6, 16-22, 24-27, 29-32, 39, and 40 are withdrawn for the reasons set forth herein.
Claims 1-5, 7-15, 23, 28, and 33-38 are being examined on the merits in this office 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 .
Denial of Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original no provisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Upon review of the instant specification, the PCT application, and provisional Appl. 62/964932, it is noted that peptides corresponding with instant SEQ ID NOs: 16-511 were not taught in the provisional application. Provisional application specification was 73 pages in length. The provisional application differs from the PCT in at least the following: the provisional did not disclose or support for X30 can be K(Z1)R6 or OrnR2; the R6 variable; or the two fatty acids (R5) at the recited amino acid positions, as recited in instant claim 1.
Instant SEQ ID NOs: 16-511 first appeared in the PCT application filed 1/21/2021. The PCT specification was 143 pages in length (not including claims).
The instant application is not entitled to the benefit of the earliest filing date. Thus, priority to provisional Appl. 62/964932 (filed 1/23/2020) is denied.
The earliest filing date for the instant application and claims is deemed to be the filing date of PCT/US2021/014302, filed 1/21/2021.
Election/Restrictions
Applicant’s election of Group I (claims 1-28 and 33-38) without traverse in the reply filed on 11/17/2025 is acknowledged.
Claims 29-32, 39, and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/17/2025.
Applicant elected the following species:
Peptide:
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Disorder: type 2 diabetes
Election was made without traverse in the reply filed on 11/17/2025.
Applicant states that claims 1-5, 7-15, 23, 28, and 33-38 read on the elected species.
Claims 6, 16-22, and 24-27 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 11/17/2025.
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.
Trademark in the Specification
The use of at least the trademark TWEEN-20® has been noted in this application at, e.g., pages 95-97 of the specification. They should be capitalized wherever they appear and be accompanied by the generic terminology. Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks.
Examiner requests that applicant thoroughly review the specification for trademark terms.
Claim Objections- multiple dependent claims
Examiner previously commented on the multiple dependent claims in the restriction requirement mailed 9/17/2025 (p. 2 of restriction).
Claims 5, 7-15, and 33-38 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent cannot depend from any other multiple dependent claim. See MPEP § 608.01(n).
Claim 4 depends from any one claims 1-3 (multiple dependent claim). Claim 3 depends from claim 1 or 2.
Claim 5 recites as claimed by any one of claims 1-4. Thus, claim 5 is a multiple dependent claim which depends from multiple dependent claim 4.
Claim 7 recites as claimed by any one of claims 1-6. Thus, claim 5 is a multiple dependent claim which depends from multiple dependent claim 4, multiple dependent claim 5, and multiple dependent claim 6.
The same analysis further applies to claims 8-15 and 33-38.
Accordingly, the claims have not been further treated on the merits.
Claim Objections
Claims 2-4, 23, and 28 are objected to because of the following informalities:
Dependent claims 2-4, 23, and 28 should be amended to recite “The [[A]] compound ..as claimed by claim
Claims 23 and 28 should be amended to recite the corresponding SEQ ID NO with the recited peptide. For instance, the first peptide recited in claim 23 is the elected species, which correlates with SEQ ID NO:11. The fifth and last peptide recited in claim 23 correlates with SEQ ID NO:15. Claim 28 recites the elected species SEQ ID NO:11.
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 1-4 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 alone or coupled with a known or disclosed correlation between structure and properties, 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 characteristics coupled with a known or disclosed correlation between properties 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 when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, the claims recite a compound of the recited peptide formula of SEQ ID NO:505. The peptide formula encompasses various amino acids for each recited position, and various C-terminal lengths depending on identity of X30 and R2 variable (SEQ ID NOs:5-10). The peptides have two fatty acid moieties (R5)- wherein two, and only two, of X10, X12, X17, X21, X24, X25, X28, X30, X31, and X40 are KZ1 or K(Z1)R6. Page 20, ll. 31-32 of the as-filed specification states: “linker” means a group conjugating the R5 fatty acid to a lysine of the peptide. As used herein, “fatty acid” means a hydrocarbon with a carboxyl group.
Thus, the claimed peptides encompass numerous peptide structures, linkers with various chemical structures and physical properties, and fatty acids having various hydrocarbon lengths and groups.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
Examples 1-5 disclose peptides of instant SEQ ID NOs:11-15, as recited in claim 23. The specification indicates that Examples 6-211 correlate with SEQ ID NOs:16-504. The specification discloses that the compounds were synthesized and binding affinities were determined (Tables 1-3).
Compounds encompassed within the instant claim scope were identified as having widely ranging binding affinities. See e.g., Ki value of SEQ ID NO:11 or 12, Ki values of SEQ ID NO:16 (Table 1); and peptides showing significantly lower efficacy in tables 2-3 (for example, Emax values of SEQ ID NOs: 11, 12, or 14, Emax value of SEQ ID NO:13, Emax value of SEQ ID NO: 15).
The claims and specification disclose compounds that do not actually fall within the instant claim scope. As noted above, the specification discloses that fatty acids [R5 variable] contain a hydrocarbon with a carboxyl group. The specification discloses fatty acids”, including, but not limited to, -(10-(4-carboxyphenoxy)decanoyl), -(4-(4-iodophenyl)butanoyl), -(4-(4-tert-butylphenyl)butanoyl), -CO-(CH2)14-CH3, -CO-(CH2)12-CH3, -CO-(CH2)10-CH3, -(7-(4-carboxyphenoxy)heptanoyl), -(11-(4-carboxyphenoxy)undecanoyl), -(12-(4-carboxyphenoxy)dodecanoyl), and -(8-(4-carboxyphenoxy)octanoyl). These compounds are not fatty acids because they do not contain a carboxyl group. For instance, the R5 variable of peptides 2-5, as recited in claim 23, are not fatty acids. R5 of Peptide 2 is -(10-(4-carboxyphenoxy)decanoyl). R5 of Peptide 3 is -(4-(4-iodophenyl)butanoyl). R5 of Peptide 4 is -(4-(4-tert-butylphenyl)butanoyl). R5 of Peptide 5 is -CO-(CH2)10-CH3.
At least, SEQ ID NOs: 12-14, 21-26, 29, 31, 32, 236-248 encompass R5 variables that are not actually fatty acids. See Table 1. Examiner notes this is not a comprehensive listing of peptides taught in the specification that structurally fail to satisfy the requirements of the instant claims.
(c) Sufficient relevant identifying characteristic in the way of complete/partial structure or physical and/or chemical properties, when coupled with known or disclosed: and (d) Representative number of examples:
As discussed above, in the instant case, based on the disclosure of the instant specification, a person of ordinary skilled in the art would not be able to determine what structural feature is required for the claimed compounds. The specification purports compounds as falling within the claim scope but the compounds are actually structurally broader in scope, e.g., R5 variables that are not fatty acids [hydrocarbon with a carboxyl group].
It is further noted that the linkers are not limited to any particular chemical composition. Linkers can include, but are not limited to, peptides, saccharides, lipids, and combinations thereof. With regard to linkers, the properties of conjugates are sensitive to the linker moiety [see section 6 in He et al, Molecules 24:1855, 1-34 (2019); see abstract and conclusion in Lu et al, Int J Mol Sci 17:561, 1-22 (2016)]. The art also recognizes that the choice of a linker has great impacts on biological activity, expression yield, and pharmacokinetic properties of a fusion partner (see Chen et al. (Adv. Drug Deliv. Rev. 65:1357-1369 (2013)).
With regard to variability in peptides, protein chemistry is probably one of the most unpredictable areas of biotechnology. 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 structure. As an example of the unpredictable effects of mutations on protein, 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 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 structure and therefore properties of the protein. The unpredictability of the effect of amino acid substitution on the structure 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 properties 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 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.
This is underscored by peptides that structurally fall within the instant claim scope, yet have significantly varying binding affinities. See above regarding Tables 1-3.
Considering the scope of the genus of instant claimed compounds of the formula of SEQ ID NO:505, the instant specification fails to provide sufficient examples to describe the entire genus of peptides sequences claimed based on limited data. The claimed compounds encompass numerous peptide structures, with linkers of variable chemical structures and physical properties, and fatty acids further having variable hydrocarbon lengths and structures.
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 claimed genus of compounds of the formula of SEQ ID NO:505; 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 4 and 23 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 4 lacks proper antecedent basis from claim 1. Claim 1 recites that variable R5 is a fatty acid. Page 20, l. 32 of the as-filed specification states: As used herein, “fatty acid” means a hydrocarbon with a carboxyl group.
Claim 4 recites a Markush grouping of R5 variable compounds. The claim recites -CO-(CH2)12-CO2H, CO-(CH2)14-CO2H, and -CO-(CH2)10-CO2H which are fatty acids [contain hydrocarbon with a carboxyl group].
Claim 4 further recites “fatty acids”: -(10-(4-carboxyphenoxy)decanoyl), -(4-(4-iodophenyl)butanoyl), -(4-(4-tert-butylphenyl)butanoyl), -CO-(CH2)14-CH3, -CO-(CH2)12-CH3, -CO-(CH2)10-CH3, -(7-(4-carboxyphenoxy)heptanoyl), -(11-(4-carboxyphenoxy)undecanoyl), -(12-(4-carboxyphenoxy)dodecanoyl), and -(8-(4-carboxyphenoxy)octanoyl) are not fatty acids because they do not contain a carboxyl group. Thus, claim 4 recites compounds that lack antecedent basis from claim 1.
Claim 23 is rejected for similar reasons. Claim 23 recites 5 separate peptides. The first recited peptide is SEQ ID NO:11, the elected species. Peptides 2-5 do not contain a fatty acid as an R5 variable. R5 of Peptide 2 is -(10-(4-carboxyphenoxy)decanoyl). R5 of Peptide 3 is -(4-(4-iodophenyl)butanoyl). R5 of Peptide 4 is -(4-(4-tert-butylphenyl)butanoyl). R5 of Peptide 5 is -CO-(CH2)10-CH3. As noted above, these compounds are not fatty acids because they do not contain hydrocarbon with a carboxyl group, as required by the definition of “fatty acids” set forth in the specification.
Closest Prior Art
The elected species of SEQ ID NO: 11 was not found to be reasonably taught or suggested by the prior art of record. The closest prior art is Abraham et al (U.S. 2020/0024322- earliest effective filing date 7/23/2018; published 1/23/2020).
Example 4 of Abraham et al discloses SEQ ID NO:13:
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X31 of this peptide is Pro, whereas X31 of instant SEQ ID NO:11 is KZ1, K((2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(γ-Glu)-CO-(CH2)12-CO2H.
Examiner further notes that the peptides of Abraham et al have no more than one of X10, X12, X13, X14, X16, X17, X19, X20, X21, X23, X24, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X39, and X40 may be a substituent that contains a fatty acid (claim 1; para. [0051]). In contrast, instant claim 1 requires 2 fatty acid moieties [R5 of KZ1 is a fatty acid]. Instant claim 1 recites “wherein two, and only two, of X10, X12, X17, X21, X24, X25, X28, X30, X31, and X40 are KZ1 or K(Z1)R6”.
Accordingly, SEQ ID NO:11 appears to be free of the prior art.
Conclusion
Claims 1-40 are pending. Claims 6, 16-22, 24-27, 29-32, 39, and 40 are withdrawn for the reasons set forth herein.
Claims 5, 7-15, and 33-38 claims have not been further treated on the merits for the reasons set forth herein [multiple dependent claims]. See MPEP § 608.01(n).
Claims 1-4 and 23 are rejected. Claim 28 is objected.
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.
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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