Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restrictions
2. Applicant's election without traverse of Group II, claims 27-38, in the reply filed on 12 February 2026 is acknowledged. Claims 1-26 and 39-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 February 2026.
3. The restriction requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, and/or Claims
4. The Response to the Restriction Requirement filed 12 February 2026 has been entered in full. Claim 1 has been amended, claims 2, 7-9, 16-17 and 45-50 have been canceled, and claims 1-26 and 39-50 have been withdrawn as discussed supra. Therefore, claims 1, 3-6, 10-15 and 18-44 are pending, and claims 27-38 are the subject of this Office Action.
Specification
Nucleotide and/or Amino Acid Sequence Disclosures
5. REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
The file name is incorrect, and the size of the text file is required to be in bytes (See image below for correct file name and size).
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Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version), with the file size in bytes;
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specifically, Applicant must provide: a substitute specification which has the appropriate statement with the file name, file creation date and file size (in bytes).
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 28-31, 34-35 and 37-38 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.
8. Claims 28-30 and 34-35 are rejected as being indefinite for reciting “conservatively modified variant”. Since it is not clear if “conservatively” refers to the structure of the substitution, the function of the PAR1- or PAR-3 derived peptide as a whole, or both, the metes and bounds of the claims cannot be determined.
9. Claim 31 is rejected as being indefinite for reciting the limitation “at least about.” Since the specification does not provide any indication as to what range is covered by the term “at least about”, the metes and bounds of the claim cannot be determined.
10. Claims 37 and 38 are rejected as being indefinite for reciting the limitation “at most about.” Since the specification does not provide any indication as to what range is covered by the term “at most about”, the metes and bounds of the claim cannot be determined.
11. Claims 37 and 38 are rejected as being indefinite for reciting the limitation “a daily dose.” Since it is not clear if the composition comprises a single dose, or multiple daily doses, and if so, for how many days, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 112, 1st Paragraph (Written Description)
12. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
13. Claims 27-38 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
14. The U.S. Court of Appeals for the Federal Circuit recently reaffirmed, in an en banc decision, that the written description requirement for a genus may be satisfied either by (i) the disclosure of a representative number of species falling within the scope of the genus or (ii) structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus. Ariad Pharmaceuticals', Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350, 94 U.S.P.Q.2d 1161, 1171 (en banc) (Fed. Cir. 2010), citing Regents" of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69, 43 U.S.P.Q.2d 1398, 1406 (Fed. Cir. 1997).
15. The representative ways of satisfying the written description requirement as set out by the Federal Circuit in Ariad Pharmaceuticals comport with statements set out in the USPTO's Manual of Patent Examining Procedure (M.P.E.P.). In particular, the M.P.E.P. provides that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species of relevant identifying characteristics. M.P.E.P. § 2163, II, A, 3, (a), (ii).
16. 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: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “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.
17. The claims are drawn very broadly to a composition comprising a PAR3-derived anti-inflammatory peptide and a PAR1-derived anti-inflammatory peptide, which the Specification teaches encompasses short oligopeptides have less than about 25 residues, as well as conservatively modified variants thereof, which can have as little as 50% sequence identity (See pp. 18 and 21, for example). The claims also recite wherein (a) the PAR3 derived anti- inflammatory peptide comprises (1) an N-terminal fragment of Metl-Arg41 deleted human PAR3 extracellular domain (SEQ ID NO:3) or conservatively modified variant thereof, wherein the fragment consists of at least the first 4 N-terminal residues of SEQ ID NO:3, or (2) at least 4 contiguous amino acid residues of PAR3 derived peptide P3R (SEQ ID NO:4) or conservatively modified variant thereof, wherein the at least 4 contiguous amino acid residues comprises Phe10- Phe12 of SEQ ID NO:4; and (b) the PAR1- derived anti-inflammatory peptide comprises (1) an N-terminal fragment of Metl-Arg46 deleted human PAR1 extracellular domain (SEQ ID NO:6) or conservatively modified variant thereof, wherein the fragment consists of at least the first 4 N- terminal residues of SEQ ID NO:6, or (2) a variant of human PAR1 derived peptide TR47 (SEQ ID NO:7) with a deletion or substitution of at least one residue at its N-terminus; or wherein the PAR3 derived peptide comprises at least the first 13 N-terminal residues of SEQ ID NO:3 or conservatively modified variant thereof, and the PAR1 derived peptide comprises at least the first 8 N-terminal residues of SEQ ID NO:6 or conservatively modified variant thereof; or wherein the PAR3 derived peptide comprises SEQ ID NO:4, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or a conservatively modified variant thereof, and the PAR1 derived peptide comprises SEQ ID NO:7, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:43, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50 or a conservatively modified variant thereof. The claims also wherein said composition comprises (a) PAR1-derived peptide comprising the sequence shown in SEQ ID NO:36 or a conservatively modified variant thereof, and (b) PAR3-derived peptide comprising the sequence shown in SEQ ID NO:9 or a conservatively modified variant thereof, wherein (a) and (b) are linked via a peptide moiety; or comprising the sequence shown in SEQ ID NO:61 or a conservatively modified variant thereof. Thus, the claims have been broadly interpreted by the Examiner as reading upon an extremely large genus of PAR3-derived anti-inflammatory peptides and a PAR1-derived anti-inflammatory peptides and fusions thereof that are only defined by a very limited structure and a desired function/activity.
18. For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
A “patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”), see MPEP 2163.IIAii.
19. Several recent court decisions speak to the notion that claiming a molecule with unknowable structural heterogeneity solely by reciting its function is not sufficient to establish possession of a genus so claimed.
20. For example, quoting Eli Lilly the court states in Ariad, 598 F.3d at 1350: "[A] sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." (quoting Eli Lilly, 119 F.3d at 1568-69).
21. A "representative number of species" means that the species which are described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG V. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
22. In the instant case, the claims encompass in their breadth a PAR3-derived anti-inflammatory peptide and a PAR1-derived anti-inflammatory peptide, which the Specification teaches encompasses short oligopeptides have less than about 25 residues, as well as conservatively modified variants thereof, which can have as little as 50% sequence identity (See pp. 18 and 21, for example), and fusions thereof linked via a peptide moiety, having the function of being an anti-inflammatory peptide.
23. Given the exceedingly large genus of fragments and variants of PAR3 and PAR1 encompassed by the claims, one of skill in the art cannot possibly envision the structures contained within this genus that will have the property of being an anti-inflammatory. While the specification provides adequate written description for a PAR3-derived peptide of SEQ ID NO: 4 (P3R) and a PAR1-derived peptide of SEQ ID NO: 7 (TR47), as well as a PAR3-PAR1 fusion protein (with a linker) comprising the amino acid sequence of SEQ ID NO: 61, which are disclosed as synergistically exerting anti-inflammatory properties via inhibiting caspase I activity and suppressing IL-1β release (See pp. 48-49, Figure 1C and 1D), this single embodiment of the invention is not representative of the unlimited breadth of the claimed invention which includes the fragments and variants recited in the claims.
24. The state of the art is such that the relationship between the sequence of a protein and its activity is not well understood and unpredictable, and that certain positions in the sequence are critical to the protein’s structure/function relationship and can only tolerate only relatively conservative substitutions or no substitutions. The problem of predicting protein and DNA structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein and DNA is extremely complex. While it is known that many amino acid substitutions are generally possible in any given protein, the positions within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g. such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitutions (see Wells, 1990, Biochemistry 29:8509-8517; Ngo et al., 1994, The Protein Folding Problem and Tertiary Structure Prediction, pp. 492-495). While Specification outlines art-recognized procedures for producing variants, this is not adequate guidance as to the nature of the active variants that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. An ordinary artisan would immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active, which conformation is dependent upon surrounding residues; therefore substitution of non-essential residues can often destroy activity. The art recognizes that function cannot be predicted from structure alone (Skolnick et al., 2000, Trends in Biotech. 18(1):34-39, especially p. 36 at Box 2; cited by Applicant).
25. Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
26. An adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”). See MPEP 2163IIA3(a).
27. Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of PAR3- and PAR-1 derived anti-inflammatory peptides encompassed in the breadth of the instant claims.
28. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that in order to satisfy the written description requirement, “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of PAR3- and PAR1-derived peptides having anti-inflammatory properties, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
29. Without a correlation between structure and function, the claims do little more than define the claimed invention by function, which is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 ("definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is"). Therefore, only a composition comprising a PAR3-derived anti-inflammatory peptide and a PAR1-derived anti-inflammatory peptide, wherein the PAR3-derived anti-inflammatory peptide comprises the amino acid sequence SEQ ID NO:4 and wherein the PAR1-derived anti-inflammatory peptide comprises the amino acid sequence SEQ ID NO:7, or a composition comprising a PAR3-PAR1 fusion having the amino acid sequence of SEQ ID NO: 61, but not the full breadth of the claims meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Summary
30. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jon M. Lockard whose telephone number is (571) 272-2717. The examiner can normally be reached on Monday through Friday, 8:00 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached on (571) 272-2911. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JON M LOCKARD/
Examiner, Art Unit 1647
April 4, 2026