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
Status of Application, Amendments, and/or Claims
2. The Response filed on 08 January 2026 has been entered in full. Claims 1, 7, 11, 13, 15-16, 18, 22, 25, 31-33 and 35 have been amended, claims 11, 24, 28 and 38 have been cancelled, and claims 39-46 have been added. New claims 39-46 will be examined as they fit under the rubric of the elected invention. Claims 13 and 37 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking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. Therefore, claims 1, 3, 7, 13, 15-16, 18-19, 22, 25, 29, 31-33, 35, 37 and 29-46 are pending, and claims 1, 3, 7, 15-16, 18-19, 22, 25, 29, 31-33, 35 and 39-46 are the subject of this Office Action.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on 26 February 2026 have been considered by the examiner.
Withdrawn Objections and/or Rejections
4. The objection to the Specification as set forth at pg. 4 of the previous Office action (mailed 06 June 2025) is withdrawn in view of Applicants filing of a Substitute Specification (filed 08 January 2026).
5. The objection to the claims as set forth at pg. 4 of the previous Office action (mailed 06 June 2025) is withdrawn in view of Applicants amendment (filed 08 January 2026).
6. The rejection of claim 24 under 35 U.S.C. 112(d) as set forth at pg. 5 of the previous Office action (mailed 06 June 2025) is moot in view of Applicants cancelation of said claim (filed 08 January 2026).
7. The rejection of claims 1, 7, 11, 15 and 31-32 for reciting an improper Markush grouping as set forth at pp. 5-6 of the previous Office action (mailed 06 June 2025) is withdrawn in view of Applicants amendment (filed 08 January 2026).
8. The rejection of claims 1, 3, 7, 11, 15-16, 19, 22, 24-25, 28-29, 31-33 and 35 under 35 U.S.C. 112(b) as set forth at pp. 7-8 of the previous Office action (mailed 06 June 2025) is withdrawn in view of Applicant’s amendment of claims 1, 7 and 25 (filed 08 January 2026).
9. The rejection of claims 11, 24 and 28 under 35 U.S.C. 112(a) (Written Description) as set forth at pp. 8-12 of the previous Office action (mailed 06 June 2025) is moot in view of Applicant’s cancellation of said claims (filed 08 January 2026).
Maintained and/or New Objections and/or Rejections
Claim Objections
10. Claims 1 and 40-46 are objected to because of the following informalities: “said peptide protein” should read “wherein said peptide, protein’. Appropriate correction is required.
Claim Rejections - 35 USC § 112
11. 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.
12. Claims 7, 29 and 31-32 are 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. The recitations “wherein said inhibitor binds to a complement C3a protein having the amino acid sequence depicted in SEQ ID NO: 43” (claim 7), “wherein the at least two inhibitors are proteins or protein fragments” (claim 29) and “wherein said inhibitor is a peptide” (claim 31) does not materially change the scope of the method from which the claims depends (claim 1) which has been amended to recite administering peptides. Claim 32 fails to include all the limitations from claim from which it depends (claim 1). Claim 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.
Claim Rejections - 35 USC § 112 (Written Description)
13. 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.
14. Claims 1, 3, 7, 15-16, 19, 22, 25, 29, 31-32 and 35 remain rejected, and newly added claims 39-46 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. The basis for this rejection is set forth at pp. 8-12 of the previous Office action (mailed 06 June 2025) and at pp. 9-12 of the Office action mailed 21 November 2024.
15. The claims are drawn quite broadly to a method comprising: treating an ocular wound, ocular fibrosis, or an ocular wound and ocular fibrosis; or pulmonary fibrosis; said treatment comprising: administering to a subject in need thereof, an inhibitor to C3a, wherein the inhibitor is a peptide, protein or protein fragment, wherein said peptide protein, or protein fragment comprises a sequence that is at least 90% identical to a sequence according to SEQ ID NO: 1-6, 13, 14, 18 or 19. The claims also recite wherein said inhibitor is a protein or protein fragment, wherein said protein or protein fragment is human C5L2 protein according to SEQ ID NO: 1, a protein/peptide or fragment that is at least 90% identical to the full-length amino acid sequence of human C5L2 protein of SEQ ID NO: 1, human C5aR1 protein according to SEQ ID NO: 2, a protein or fragment that is at least 90%identical to the full-length amino acid sequence of human C5aR1 protein of SEQ ID NO: 2, human C3aR protein according to SEQ ID NO: 3, a protein or fragment that is at least 90% identical to the full-length amino acid sequence of human C3aR protein as of SEQ ID NO: 3, a mouse C5L2 protein according to SEQ ID NO: 4, a protein or fragment that is at least 90% identical to the full-length amino acid sequence of mouse C5L2 protein of SEQ ID NO:4, mouse C5aR1 protein according to SEQ ID NO: 5, a protein or fragment that is at least 90% identical to the full-length amino acid sequence of mouse C5aR1 protein of SEQ ID NO: 5, mouse C3aR protein according to SEQ ID NO: 6,and or a protein or fragment that is at least 90% identical to the full-length amino acid sequence of mouse C3aR protein of SEQ ID NO: 6. The claims also recite wherein said inhibitor is a protein according to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6 or a fragment thereof. The claims also recite wherein the inhibitor is a protein according to SEQ ID NO: 1 or SEQ ID NO: 4 or a fragment thereof, or a protein or fragment thereof having at least 90% to a protein according to SEQ ID NO: 1 or SEQ ID NO: 4 or a fragment thereof. The claims also recite a method comprising: treating an ocular wound, ocular fibrosis, or an ocular wound and ocular fibrosis, or pulmonary fibrosis; said treatment comprising: administering to a subject in need thereof, an inhibitor to C3a, wherein the inhibitor is a peptide, protein or protein fragment, wherein said peptide protein, or protein fragment comprises a sequence according to SEQ ID NO: 1-6, 13, 14, 18, or 19 wherein no more than two amino acids of said respective sequence are substituted by a different amino acid; wherein said peptide protein, or protein fragment comprises the sequence according to SEQ ID NO: 13 or 14 wherein no more than two amino acids of said respective sequence are substituted by a different amino acid; wherein said peptide protein, or protein fragment comprises a sequence according to SEQ ID NO: 18 or 19 wherein no more than two amino acids of said respective sequence are substituted by a different amino acid; wherein said peptide protein, or protein fragment comprises the sequence that is SEQ ID NO: 18 or 19 or a sequence that is at least 90% identical to SEQ ID NO: 18 or 19; wherein said peptide protein, or protein fragment comprises the sequence that is at least 90% identical to SEQ ID NO: 13 or 14; wherein said peptide protein, or protein fragment comprises the sequence that is at least 90% identical to SEQ ID NO: 18 or 19; wherein said peptide protein, or protein fragment comprises the sequence according to SEQ ID NO: 1 or 4, wherein no more than two amino acids of said respective sequence are substituted by a different amino acid; or wherein said peptide protein, or protein fragment comprises the sequence that is at least 90% identical to SEQ ID NO: 1 or 4. Thus the claims are drawn to a method of treatment utilizing an extremely large genus of peptide inhibitors to C3a that are only defined a by a very limited structure and a desired function.
16. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, and any combination thereof. However, there does not appear to be an adequate written description in the specification as filed of proteins or fragments thereof having as little as 90% sequence identity to mouse or human C5L2, C5aR1 and C3aR proteins which are capable of binding and inhibiting the activity of C3a.
17. It is well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. While it is known that 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 art-recognized procedures for designing and producing variants is known, such does not provide adequate written description of the active variants that may be constructed, since 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).
18. In the instant case, there is insufficient guidance to direct a person of skill in the art to select or predict particular residues of the recited C5L2, C5Ar1 and C3AR proteins as essential for binding and inhibiting C3a. While the specification provides adequate written description for the human and mouse C3aR proteins (SEQ ID NOs: 3 and 6, respectively), which was shown to inhibit myofibroblasts activated by C5a in human corneal keratocytes (See Examples 26-27, for example), the C5L2 proteins of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 18 and SEQ ID NO: 19, C5AR1 proteins of SEQ ID NO: 2 and SEQ ID NO:5, and the proteins of SEQ ID NO: 13 and SEQ ID NO: 14 which are conserved across C5L2, C5aR1 and C3aR and contained within the proteins of SEQ ID NO: 18 and SEQ ID NO: 19, respectively, it does not provide adequate written description for the genus of variants encompassed by the claims since the art recognizes that function cannot be predicted from structure alone. The distinguishing characteristics of the claimed genus are not described. The only adequately described species of polypeptides comprising the amino acid sequence of SEQ ID NOs:1-6, 13-14 and 18-19. Accordingly, the specification does not provide adequate written description of the claimed genus.
19. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “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).
20. With the exception of the polypeptides referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed agonists, 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 product 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.
21. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
22. Therefore, only peptide inhibitors of C3a comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 18 and SEQ ID NO: 19, but not the full breadth of the claims, meet 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).
Response to Arguments
23. Applicant’s arguments as they pertain to the rejections have been fully considered but are not persuasive for the following reasons.
24. Applicant argues at pp. 9-10 of the response (filed 08 January 2026) that the scope of the inhibitors have ben specified, the inclusion of “a fragment thereof” has been removed.
25. Applicant's arguments have been fully considered but are not found persuasive for the following reasons. While the scope of the inhibitors has been narrowed by the amendment, the claims still recite variants. While the specification provides adequate written description for the human and mouse C3aR proteins (SEQ ID NOs: 3 and 6, respectively), which was shown to inhibit myofibroblasts activated by C5a in human corneal keratocytes (See Examples 26-27, for example), the C5L2 proteins of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 18 and SEQ ID NO: 19, C5AR1 proteins of SEQ ID NO: 2 and SEQ ID NO:5, and the proteins of SEQ ID NO: 13 and SEQ ID NO: 14 which are conserved across C5L2, C5aR1 and C3aR and contained within the proteins of SEQ ID NO: 18 and SEQ ID NO: 19, respectively, it does not provide adequate written description for the genus of variants encompassed by the claims since the art recognizes that function cannot be predicted from structure alone. For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species, cannot be achieved by disclosing only one or two species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph. In the instant case, the distinguishing characteristics of the claimed genus are not described. The only adequately described species of inhibitors that read on the elected species of proteins/protein fragments that bind C3a are the polypeptides of SEQ ID NOs:1-6, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 18 and SEQ ID NO: 19, and the description of 10 species of protein inhibitors which bind C3a is not adequate written description of an entire genus of fragments and variants that are encompassed by the claims.
Summary
26. No claim is allowed.
27. Claims 18 and 33 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
28. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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 M-F 9-6 EST.
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/J.L/Examiner, Art Unit 1647 March 16, 2026
/Christine J Saoud/Primary Examiner, Art Unit 1645