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 .
Priority
This application is a CON of PCT/CN2020/138950 filed 12/24/2020 and claims the benefit of the priority of Chinese patent application No. CN202010952921.3 filed 09/11/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 03/15/2023 has been considered by the examiner.
Election/Restrictions
Claims 3-11 are withdrawn from further consideration pursuant to 37 CFR
1.142(b) as being drawn to a nonelected Group II and III or based on the elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/21/2025. Applicant’s election without traverse of Group I drawn to proinsulin glargine, in the reply filed on 11/21/2025 is acknowledged.
Applicant further elects the species of R being SEQ ID NO: 3, R1 is Arginine, and the sequence (B1-B32)-(A1-A20)-A21 is SEQ ID NO: 6.
Claim Status
Claims 1-11 are pending. Claims 3-11 are withdrawn. Claims 1-2 are being examined on the merits in this office action.
Drawings
The drawings are objected to because Figures 1-7, and 9-10 are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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.
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.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Borowicz et al. (WO2017126984A1 – hereinafter “Borowicz”) in view of French et al. (J. Mol. Evol. (1983) 19:171-175).
Borowicz teaches a polypeptide having the amino acid sequence of the formula:
Xn-B-Arg-Arg-A
where:
A is a polypeptide of the insulin A-chain or analogue thereof, preferably a sequence selected from SEQ. ID No.: 1-4. B is a polypeptide of the insulin B-chain or analogue thereof, preferably a sequence selected from SEQ. ID No.: 5-7. n is 0 or 1, X is a leader protein polypeptide, preferably of a sequence selected from SOD of SEQ. No: 8 or UBI of SEQ. No: 9 (claim 1). Borowicz teaches that A21 is Gly (Page 4, line 3rd paragraph, line 2; page 18, Example 6).
Borowicz teaches that the human insulin B chain is bound to the A chain via Arg-Arg dipeptide and teaches the sequence of SEQ ID NO: 10, which has the sequence below
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Examiner notes that the highlighted sequence is the instant sequence SEQ ID NO: 6, while the sequence from residues 1-64 is the SOD sequence. Examiner notes that the difference between the proinsuline glargine of the Borowicz and the instant claims is that the SOD sequence is different from the instant sequence in the places wherein the lysine residues in positions correlating to the instant X1, X2 and X3 are replaced with a histidine (see position correlating to the instant X1, X2 and X3).
Examiner notes that as taught by French et al., lysine can be conservatively substituted with histidine (see page 172, left col., 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the SOD sequence of Borowicz and conservatively substitute the lysine in the SOD sequence for histidine because this constitute obvious to try given the finite number of options in the substitution in that group. One of ordinary skill in the art would find it obvious to try and conservatively substitute lysine with histidine to arrive to the instant SOD sequence since lysine can be substituted with a finite number of options (K, R, or H) or predictable solutions with a reasonable expectation of success. The disclosures render obvious claim 1.
Regarding claim 2, Examiner notes that the disclosures render obvious substitution lysine in the three position with histidine to arrive to the instant SEQ ID NO: 3, thus rendering obvious claim 2.
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 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. US12325732B2 in view of Borowicz et al. (WO2017126984A1 – hereinafter “Borowicz”).
The claims of the patent recite a novel short-proinsulin aspart sequence for preparing recombinant insulin aspart and analogs thereof, wherein the sequence has an amino acid sequence as shown in Formula I: R-R1-(B1-B27)-B28-B29-B30-R2-(A1-A21),
wherein R-R1 is a leading peptide sequence, which meets the following conditions:
(a) R is one part of super oxide dismutase (SOD) homolog, which consists of 63 amino acids including active methionine; and two cysteine (C) residues are substituted by serine(S);
wherein, the sequence of R is SEQ ID NO: 1:
MATHAVSVLKGDGPVQGIINFEQHESNGPVKVWGSIHGLTEGLHGFHVHE FGDNTAGSTSAGP;
(b) the leading peptide does not affect refolding of short-proinsulin aspart and can be cleaved;
(c) R1 is any one of Arg and Lys,
R2 is a C-peptide, which consists of any one from Arg or Lys;
B1-B27 denotes an amino acid sequence of B1 to B27 in B-chain of native human insulin;
A1-A21 denotes an A-chain of native human insulin; B28 is Aspartic acid; B29 is Lysine; and B30 is Threonine; (claim 1-3).
The difference between the sequence of the patent and the instant sequence is that in the instant sequence, the B chain is covalently bound to the A chain via a Arg-Arg dipeptide, while in the claims of the patent, the chains are covalently bound by either Arg or Lys.
However, it is known in the art, before the effective filing date of the claimed invention, that the two chains can be covalently bound via a Arg-Arg dipeptide as taught by Borowicz et al. Borowicz teaches a polypeptide having the amino acid sequence of the formula:
Xn-B-Arg-Arg-A
where: A is a polypeptide of the insulin A-chain or analogue thereof, preferably a sequence selected from SEQ. ID No.: 1-4. B is a polypeptide of the insulin B-chain or analogue thereof, preferably a sequence selected from SEQ. ID No.: 5-7. n is 0 or 1, X is a leader protein polypeptide, preferably of a sequence selected from SOD of SEQ. No: 8 or UBI of SEQ. No: 9 (claim 1). Borowicz teaches that A21 is Gly (Page 4, line 3rd paragraph, line 2; page 18, Example 6). Borowicz teaches that the human insulin B chain is bound to the A chain via Arg-Arg dipeptide (claim 3). Further, Borowicz teaches that the linker sequences used in the invention were 1. Lys-Arg, 2. Arg, 3. Arg-Arg and 4. C-peptide (See Page 5, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sequence of the patent and link the B chain to the A chain using other linker sequences such as Arg-Arg, since Borowicz teaches the same instant peptide, arranged in the instant way, and teaches covalently binding the B chain to the A chain using several linker sequence including Arg, Lys, or the dipeptide Arg-Arg. Thus, one of ordinary skill in the art would have had a reasonable expectation of success in using other linker sequences such as those taught by Borowicz. The claims of the patent render obvious the instant claim 1.
Regarding claim 2, the claims of the patent recite that R is SEQ ID NO: 1:
MATHAVSVLKGDGPVQGIINFEQHESNGPVKVWGSIHGLTEGLHGFHVHE FGDNTAGSTSAGP; (claim 1), which is identical to the instant SEQ ID NO: 3.
Nucleotide and/or Amino Acid Sequence Disclosures
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:
via EFS-Web (see Section I.1 of the Legal Framework for EFS-Web (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 identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
on compact disc(s) in duplicate according to 37 CFR 1.52(e)(1)(ii) and (4), labeled according to 37 CFR 1.52(e)(6), together with a statement that the duplicate compact discs are identical and an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(5) 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;
via EFS-Web as a PDF (not recommended); or
on paper.
37 CFR 1.821(e) requires that a copy of the "Sequence Listing" must also be submitted in computer readable form (CRF) in accordance with the requirements of 37 CFR 1.824.
If a "Sequence Listing" ASCII text file submitted via EFS-Web on the application filing date complies with the requirements of 37 CFR 1.824(a)(2) - (6) and (b), and applicant has not filed a "Sequence Listing" as a PDF, the text file will serve as both the "Sequence Listing" required by 37 CFR 1.821(c) and the CRF required by 37 CFR 1.821(e), and the statement of identity under the "Legal Framework" is not required.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web as a PDF, then the "Legal Framework" requires submission of a statement that the "Sequence Listing" content of the PDF copy and the ASCII text file copy submitted via EFS-Web are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or compact disc, then 37 CFR 1.821(f) requires submission of a statement that the "Sequence Listing" content of the paper or compact disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below. All sequences disclosed in the application must comply with the requirements of 37 C.F.R. 1.821-1.825, not only those recited in the claims.
The sequence in claim 1 does not contain a SEQ ID NO identifier.
All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database.
Applicant is advised to amend claim 1 to recite a SEQ ID NO. for the amino acid sequences contained therein. If the corresponding sequences are not present in the sequence listing filed on 03/10/2023, Applicants are requested to submit an updated sequence listing containing all the sequences disclosed in the instant application, as appropriate.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 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 G. 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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/MERCY H SABILA/Examiner, Art Unit 1654