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.
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Claims 3-11 are withdrawn from further consideration pursuant to 37 CFR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Claim Rejections - Withdrawn
The rejection of claim 1 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 (1983) 19:171-175) is withdrawn in view of the claim amendments and the new claims.
The rejection of claim 1 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 (WO2017126984A1 – hereinafter “Borowicz”) is withdrawn in view of the approved terminal disclaimer.
Drawings - Withdrawn
The objection to the drawings is withdrawn in view of the amended Drawings.
Claim Status
Claims 1, 3-19 are pending. Claims 3-11 are withdrawn. Claim 1 is amended. Claim 2 is canceled. Claims 12-19 are new. Claims 1, and 12-19 are being examined on the merits in this office action.
Claim Rejections - 35 USC § 103 – New
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, and 12-19 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) and Bolli et al. (The Lancet, 356: 9228, 2000, 443-445).
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 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. Examiner further notes that sequence SEQ ID NO:10 of Borowicz shown above shows that the residue at position 64 is an Arginine , which reads on the instant R1. Additionally, from the sequence of Borowicz reproduced above, residues 65-94, is B (B chain), which reads on the instant B1-B30. Residues 95-96 are two Arginine residues which reads on the instant B31-B32 being two Arginine residues behind C-terminal of B30 site. Residues 97-116 is the insulin A chain, which reads on the instant A1-A20, and Borowicz teaches that A21 is Gly (Page 4, line 3rd paragraph, line 2; page 18, Example 6).
Examiner notes that the sequence of Borowicz from residues 1-63 is the SOD sequence which is the instant R. Examiner notes that the difference between the proinsulin 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 position 2, 24, and 37 are replaced with a histidine.
Examiner notes that as taught by French et al., lysine can be conservatively substituted with histidine (see page 172, left col., 2nd paragraph).
Bolli teaches the insulin glargine with (21A-Gly-30Ba-L-Arg-30Bb-L-Arg human insulin) and is produced by recombinant DNA technology and further teaches that the addition of two positive charges (two arginine molecules) to the C-terminus of the B chain, which shifts the isoelectric point from a pH of 5·4 to 6·7, making the molecule more soluble at a slightly acidic pH and less soluble at the physiological pH of subcutaneous tissue and further teaches the replacement of A21 asparagine by glycine is charge neutral and associated with good stability of the resulting human insulin analogue (Page 443, left col., 2nd paragraph, line 1-9). Bolli further teaches that the insulin glargine, because of its stability, absorption of insulin glargine from the subcutaneous site of injection is delayed and lasts a long time, thus providing a fairly constant basal insulin supply, much like that of basal insulin secretion in non-diabetic people in the post-absorptive state (Page 443, 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. Additionally, it would have been obvious to infer that the addition of the two Arginine residues would enhance the expression of insulin as recited in claim 13, since Bolli teaches that the insulin glargine with two Arginine residues is stable and lasts long when injected provides a fairly constant basal insulin supply. 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 claims 1 and 16.
Regarding claims 12 and 17, Borowicz teaches the instant proinsulin glargine. Borowicz further teaches that digestion of the peptide with trypsin (Page 4, line 7-8; page 14, step 10). Examiner further notes that the limitations of claim 12 constitute an expected result of the product. MPEP 2111.04 states: claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In the instant case, the limitation expresses the intended result of the product and is given little patentable weight. Additionally, since Borowicz teaches the same compound as the instant invention, the features of the compound are inherent having the same function or properties.
Regarding claims 13-14, and 18-19, Bolli teaches the insulin glargine with (21A-Gly-30Ba-L-Arg-30Bb-L-Arg human insulin) and is produced by recombinant DNA technology and further teaches that the addition of two positive charges (two arginine molecules) to the C-terminus of the B chain, which shifts the isoelectric point from a pH of 5·4 to 6·7, making the molecule more soluble at a slightly acidic pH and less soluble at the physiological pH of subcutaneous tissue and further teaches the replacement of A21 asparagine by glycine is charge neutral and associated with good stability of the resulting human insulin analogue (Page 443, left col., 2nd paragraph, line 1-9). Bolli further teaches that the insulin glargine, because of its stability, absorption of insulin glargine from the subcutaneous site of injection is delayed and lasts a long time, thus providing a fairly constant basal insulin supply, much like that of basal insulin secretion in non-diabetic people in the post-absorptive state (Page 443, left col., 2nd paragraph). It would have been obvious to infer that the addition of the two Arginine residues would enhance the expression of insulin as recited in claim 13, since Bolli teaches that the insulin glargine with two Arginine residues is stable and lasts long when injected provides a fairly constant basal insulin supply.
Regarding claims 15, 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 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.
Response to Arguments
Applicant’s arguments, see Applicant Arguments, filed 04/08/2026, with respect to the rejection(s) of claim(s) 1, 12-19 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Bolli et al.
Conclusion
No claims are allowed.
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.
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.
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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
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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