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 .
Election/Restrictions
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Applicant's election with traverse of, Group I, claims 1-10, 12, and 16-19, in the reply filed on 5/13/2026 is acknowledged. The traversal is on the ground(s) that Pecorari describes randomized Sac7d libraries and Bansal identifies C3/C3b as therapeutic targets, neither reference teaches or suggests the presently claimed Sac7d variants defined by specific mutations (including W24Y and R42W) and selected for binding to C3 and/or C3b. Nor do they provide guidance that would have led a person of ordinary skill in the art to select such variants presenting these mutations from the vast number of possibilities within Pecorari's randomized libraries. This is not found persuasive because Pecorari's randomized library corresponds to the randomization of the residues K7, Y8, K9, W24, V26, M29, S31, T33, R42, A44 and S46 of Sac7d (p5, line 29-30; p10, SEQ ID NO: 1). Pecorari et al. teach randomization of the residues by degenerated oligonucleotides encoding NNS triplets (wherein N=A,C,T or G, and S=C or G), a DNA product including the 5' - flanking region necessary for ribosome display to generate a protein library (p13, line 20-26), demonstrating the randomized residue mutations at W24 and R42 of Sac7d inherently comprise mutations of W24Y (DNA codon sequence TA[T/C] for Y) and R42W (DNA codon sequence TGG for W) as claimed. Pecorari et al. teach the engineered mutant Sac7d proteins comprising mutations at W24 and R42 in randomized libraries capable of binding to a target protein of interest with virtually no limitation (p7, line 26-32). Igawa et al. teach the use of randomization of selected amino acids in a polypeptide or framework sequence (p95, line 31-34) by PCR and site-directed mutagenesis known in the art (p95, line 25-26). Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3, C3a and C3b (p21, line 29). Bansal shows C3 and C3b are important proteins in complement pathway (Fig 1). Bansal suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10]. Because (a) Pecorari et al. teach the engineered mutant Sac7d proteins comprising mutations at W24 and R42 in randomized libraries capable of binding to a target protein of interest with virtually no limitation (p7, line 26-32) including binding to C3 and/or C3b, (b) Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3, C3a and C3b (p21, line 29), and (c) Bansal suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10], one of ordinary skill in the art would have found it obvious to isolate a peptide of mutant Sac7d comprising randomized residue mutations at W24 and R42 (inherently comprising W24Y and R42W mutations) able to bind C3 and/or C3b. The combination would have reasonable expectation of success because both Pecorari et al. and Igawa et al. suggest the use of a randomized ribosome display peptide library to isolate C3 and/or C3b binding peptide (Pecorari et al. p7, line 26-32; Igawa et al. p21, line 29). Once a reference teaching product (the randomized residue mutations at W24 and R42 in Pecorari’s Sac7d protein library inherently comprising W24Y and R42W) appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency (randomized library), the burden of production shifts to the applicant. See MPEP 2112 (V). Applicant failed to provide any data to support opinions or arguments; thus, the requirement is still deemed proper and is therefore made FINAL.
Claims 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected method invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/13/2026.
Applicant elected species in response to species election are shown follows, reading on claims 1-2, 4-5, 7-9, and 12. Thus, claims 3, 6, 10, and 17-19 are further withdrawn.
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Claim Status
Claims 1-19 are pending.
Claims 3, 6, 11, and 13-19 are withdrawn as being directed to a non-elected method invention or non-elected species, the election having been made with traverse on 5/13/2026.
Claims 1-2, 4-5, 7-10, and 12 have been examined.
Priority
This application is a 371 of PCT/EP2022/057163 filed on 03/18/2022, which claims foreign priority of EP 21305336.6 filed on 03/18/2021 and EP 21305904.1 filed on 06/30/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/18/20123 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 contains the acronyms “C3” and C3b, and an acronym in the first instance of claims should be expanded upon/spelled out as “complement component 3” and “complement component 3b” with the acronym indicated in parentheses as (C3) and (C3b) respectively. The abbreviations can be used thereafter.
Appropriate correction is required.
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.
Claims 1-2, 4-5, 7-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Pecorari et al. (WO 2008/068637 A2, cited in IDS) in view of Igawa et al. (CA 2931296) and Bansal et al. (WO 2013/152024 A1, cited in IDS).
Claim 1 is drawn to a polypeptide comprising a variant of Sac7d family protein comprising W24Y and R42W and up to 4-20 mutations in the interface of its natural ligand-binding site corresponding to SEQ ID NO: 1 capable of binding to C3 and/or C3b.
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Pecorari et al. teach randomization of the residues of its binding face of a protein to create engineered molecules able to bind specifically and high affinity to target proteins (p1, line 19-24). Pecorari et al. teach a reference/parent protein is Sac7d from Sulfolobus acidocaldarius (p1, line 26-38) as shown follows (p10, SEQ ID NO: 1) with 100% identity to the instant SEQ ID NO: 1. Pecorari's randomized library 11 corresponds to the randomization of the residues K7, Y8, K9, W24, V26, M29, S31, T33, R42, A44 and S46 of Sac7d (p5, line 29-30; p10, SEQ ID NO: 1). Pecorari et al. teach randomization of the residues by degenerated oligonucleotides
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encoding NNS triplets (wherein N=A,C,T or G, and S=C or G), a DNA product including the 5' - flanking region necessary for ribosome display to generate a protein library (p13, line 20-26), demonstrating the randomized residue mutations at W24 and R42 of Sac7d inherently comprise mutations of W24Y (DNA codon sequence TA[T/C] for Y) and R42W (DNA codon sequence TGG for W) as claimed. Pecorari et al. teach the engineered mutant Sac7d proteins comprising mutations at W24Y and R42W in the randomized libraries capable of binding to a target protein of interest with virtually no limitation (p7, line 26-32). Pecorari et al. further teach the engineered mutant Sac7d proteins as an alternative scaffold to antibodies (p33, line 14-15).
Pecorari et al. did not explicitly teach isolation of peptides capable of binding to C3 and/or C3b from the ribosome display peptide library.
Igawa et al. teach ribosome display peptide library and phage display library are common techniques for peptide library design (p57, line 9-14; p88, line 35). Igawa et al. teach the use of randomization of selected amino acids in a polypeptide or framework sequence (p95, line 31-34) by PCR and site-directed mutagenesis known in the art (p95, line 25-26). Igawa et al. teach a randomized amino acid comprising Ile, Ala, Asp, Glu, Phe, Gly, Lys, Leu, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr corresponding to a specified amino acid position (p101, line 24), further demonstrating presence of W24Y and R42W in Pecorari’s peptide library. Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3, C3a and C3b (p21, line 29). Thus, one of ordinary skill in the art would expect to screen Pecorari’s ribosome display peptide library against C3 or C3b to isolate an engineered peptide capable of binding to C3 and/or C3b. Bansal shows C3 and C3b are important proteins in complement pathway (Fig 1). Bansal suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10], which motivates one of ordinary skill in the art to screen Pecorari's randomized library against C3 or C3b protein to isolate C3 and/or C3b binding peptides to treat a complement-mediated disease as suggested by Bansal et al. [0002].
Because (a) Pecorari's randomized library 11 corresponds to the randomization of the residues K7, Y8, K9, W24, V26, M29, S31, T33, R42, A44 and S46 of Sac7d (p5, line 29-30; p10, SEQ ID NO: 1) and Pecorari et al. teach the engineered mutant Sac7d proteins comprising mutations at W24Y and R42W in randomized libraries capable of binding to a target protein of interest with virtually no limitation (p7, line 26-32), (b) Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3, C3a and C3b (p21, line 29), and (c) Bansal shows C3 and C3b are important proteins in complement pathway (Fig 1) and suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10], which motivates one of ordinary skill in the art to screen Pecorari's randomized library against C3 or C3b protein to isolate C3 and/or C3b binding peptides to treat a complement-mediated disease as suggested by Bansal et al. [0002].
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Pecorari et al. and (ii) Igawa et al. in view of Bansal because (a) Pecorari et al. teach engineered mutant Sac7d proteins comprising mutations of W24Y and R42W in a randomized ribosome display peptide library capable of binding to a target protein of interest with virtually no limitation (p7, line 26-32), (b) Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3 and/or C3b (p21, line 29) as suggested by Pecorari et al., and (c) Bansal shows C3 and C3b are important proteins in complement pathway (Fig 1) and suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10], which motivates one of ordinary skill in the art to screen Pecorari's randomized library against C3, C3a or C3b to isolate C3 and/or C3b binding peptide to treat a complement-mediated disease as suggested by Bansal et al. [0002]. The combination would have reasonable expectation of success because both Pecorari et al. and Igawa et al. suggest the use of a randomized ribosome display peptide library to isolate C3 and/or C3b binding peptide (Pecorari et al. p7, line 26-32; Igawa et al. p21, line 29).
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With respect to claims 2, 4-5, and 7, Pecorari et al. teach a reference/parent protein is Sac7d (p10, SEQ ID NO: 1) with 100% identity to the instant SEQ ID NO: 1 from Sulfolobus acidocaldarius (p1, line 26-38). Pecorari's randomized library 16 corresponds to the randomization of the bold residues K7, Y8, K9, K21-22, W24, V26, K28, M29, S31, T33, K39, T40, R42, A44 and S46 of Sac7d (p10, SEQ ID NO: 1) as shown follows. Pecorari et al. teach randomization of the residues by degenerated oligonucleotides encoding NNS triplets (wherein N=A,C,T or G, and S=C or G), a DNA product
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including the 5' - flanking region necessary for ribosome display to generate a protein library (p13, line 20-26), demonstrating the randomized residue mutations at W24 and R42 of Sac7d inherently comprise mutations of W24Y (DNA codon sequence TA[T/C] for Y) and R42W (DNA codon sequence TGG for W). A sequence alignment of Pecorari’s randomized library compared to the elected peptide SEQ ID NO: 82 shows amino acid positions 7-9, 21-22, 24, 26, 29, 31, 33, 40, 42, and 44 are all selected for randomization as shown follows. Thus, Pecorari's randomized library inherently or intrinsically comprises the claimed C3 and/or C3b binding peptide as claimed. Igawa et al. teach a ribosome display peptide library comprising randomization of selected amino acids in a polypeptide or framework sequence can be used to identify an antigen-binding peptide sequence bound to cellular proteins of C3, C3a and C3b (p21, line 29). Bansal shows C3 and C3b are important proteins in complement pathway (Fig 1) and suggests the use of an engineered protein to bind C3b (e.g., anti-C3b antibody) and inhibit C3b formation [0025, Fig 10], which motivates one of ordinary skill in the art to screen Pecorari's randomized library against C3 or C3b to isolate C3 and/or C3b binding peptide to treat a complement-mediated disease as suggested by Bansal et al. [0002]. Therefore, one or ordinary skill in the art would have found it obvious to screen Pecorari's randomized library to isolate C3 and/or C3b binding peptides with reasonable expectation of success as suggested by Igawa et al.
With respect to claim 8, one or ordinary skill in the art would have found it obvious to screen Pecorari's randomized library to isolate C3 and/or C3b binding peptides with reasonable expectation of success as suggested by Igawa et al. see rejection of claims 2, 4-5, 7, and 18-19 above.
With respect to claims 9-10, Pecorari et al. suggest a selected binding peptide (e.g., a C3 or C3 binding peptide isolate from Pecorari's randomized library) further fusion, reading on conjugation, to a reporter protein of PhoA or GFP (p33, line 19-20).
With respect to claim 12, Igawa et al. teach formulation of an antigen binding molecule with a pharmaceutically acceptable carrier (p157, line 10-11). Thus one of ordinary skill in the art would have found it obvious to beneficially combine a library selected C3 and/or C3b binding peptide with a pharmaceutically acceptable carrier to formulate a pharmaceutical composition.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4, and 7-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 32 of copending Application No. 18/282,664 (the ‘664 application, 4/24/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘664 application disclosed a peptide obvious to the instant application.
Claim 1 of the ‘664 application disclosed a chimeric polypeptide comprising a C3 and/or C3b binding domain of SEQ ID NO: 77 and VEGF inhibitor.
Claim 32 of the ‘664 application disclosed the C3 and/or C3b binding peptide sequence as SEQ ID NO: 17 reading on the elected species of SEQ ID NO: 82. Thus, claims 1 and 32 of the ‘664 application satisfy the instant claims 1-2, 4, and 7-8.
Claim 1 of the ‘664 application disclosed a chimeric polypeptide comprising a C3 and/or C3b binding domain of SEQ ID NO: 77 and VEGF inhibitor. The specification disclosed VEGF inhibitor in claim 1 of the ‘664 application as a protein of VEGF-binding fragment [00133], satisfying the instant claims 9-10.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
22-July-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights