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
Applicant's election with traverse of Group 1 and species capping group 13 in the reply filed on 7/21/2026 is acknowledged. However, applicants did not elected species for variant positions for insulin A-chain and B-chain as required for species Group “C” or SEQ ID for insulin A-chain and B-chain as required at pg. 5-6 of the restriction requirement of 6/1/2026. In order to further the examination, the examiner is selecting insulin A-chain having amino acid sequence of SEQ ID NO: 1, and insulin B-chain having amino acid sequence of SEQ ID NO: 2 as recited in claim 11. The traversal is on the ground(s) that there is a single general inventive concept presently claimed compound of inulin of A-chain and insulin B-chain. This is not found persuasive because insulin A-chain having the amino acid sequence of SEQ ID NO: 1 and the B-chain having amino acid sequence of SEQ ID NO: 2 are well known in the art as disclosed at pg. 18 of the specification.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1-22 are pending.
Claims 19-20 are withdrawn for being drawn to a non-elected invention (i.e., Group 2).
Claims 1-18 and 21-22 are under examination to the extent they read on elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 5/3/2023 and 9/30/2024 have been considered.
Claim Objections
Claims 3-5 and 13 are objected to because of the following informalities: Claims 3-5 and 13 are objected for the use of many abbreviated phrases ( PEG, AEG, AEG-C6, and many more), which should be described for the first time followed by an abbreviated form placed in a bracket.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 3-5 and 13 is 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.
Claims 3-5 recite the limitation "the capping group" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 4 and 13 recite “….R’ is H (when R is R’NH-)..” this unclear if the parenthetical is exemplary language or not. Specifically, it is unclear if the parenthetical is an attempt to limit the scope of “R’ is H” to only the situation of when R is R’NH, or if R; may hydrogen (H) in all circumstances regardless of whether or not R’ is R’NH (see e.g., MPEP 2178.05(d)).
It is noted to applicants that the broadest reasonable interpretation of claim 2 limitation “the amines of the B-29 lysine or B-28and the N-terminal amino acids of each of the B-chain of the two insulins optionally and independently are conjugated with a capping group” makes the limitation of conjugating with a capping agent not required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claim 9 is 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description in this case only sets forth an insulin dimer wherein each dimer comprises an A-chain polypeptide and a B-chain polypeptide, wherein the A-chain polypeptide comprises amino acid sequence of SEQ ID NO: 1, 7, 10; and the B-chain polypeptide comprises amino acid sequence of SEQ ID NO:2, 6-9, 11 or 12, and therefore the written description is not commensurate in scope with “wherein each A-chain polypeptide independently comprises the amino acid sequence GX2X3EQCCX8SICSLYQLX17NX19CX23 (SEQ ID NO:3) and each B-chain polypeptide independently comprises the amino acid sequence X25LCGX29X30LVEALYLVCGERGFX27YTX31X32 (SEQ ID NO:4) or X22VNQX25X26CGX29X30LVEALYLVCGERGFX27YTX31X32X33X34X35 (SEQ ID NO:5) wherein X2 is isoleucine or threonine; X3 is valine, glycine, or leucine; X8 is threonine or histidine; X17 is glutamic acid or glutamine; X19 is tyrosine, 4-methoxy- phenylalanine, alanine, or 4-amino phenylalanine; X23 is asparagine or glycine; X22 is or phenylalanine and desamino-phenylalanine; X25 is histidine or threonine; X26 is leucine or glycine; X27 is phenylalanine or aspartic acid; X29 is alanine, glycine, or serine; X30 is histidine, aspartic acid, glutamic acid, homocysteic acid, or cysteic acid; X31 is aspartic acid, proline, or lysine; X32 is lysine or proline; X33 is threonine, alanine, or absent; X34 is arginine or absent; and X35 is arginine or absent; with the proviso at least one of X31 or X32 is lysine”.
The claims broadly encompass thousands of variants of insulin A-chain polypeptide at six different positions, and at many thousands of insulin B-chain polypeptide variants at 11 different positions, wherein the insulin dimers must have insulin receptor agonist function.
The specification on pg.202-204, discloses that insulin A-chain polypeptides having amino acid sequences of SEQ ID NO: 1, 7 and 10 and insulin B-chain polypeptides having amino acid sequence of SEQ ID NO: 2, 6, 8, 9 and 11-12. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
The specification at pg. 14-19 discloses insulin analogs such as inulin aspart (NOVOLOG), insulin lispro (HUMALOG), glargine are known in the art. However, the instant claim 9 is drawn to many thousands if not millions of derivative having mutation at 15-17 amino acid positions within insulin A-chain and B-chain. The specification does not describe a representative number of variants of insulin A-chain and B-chain comprising variants at claimed positions of insulin analog. The problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinants to ascertain functional aspects of the protein 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 success are limited. Certain positions in the sequence are critical to the protein’s structure/function relationship, 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 substitution ( Bowie et al., 1990, Science 247: 1306-1310, page. 1306, column 2, paragraph2; Wells, 1990, Biochemistry 29:8509-8517). In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, 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, for purposes of the written description inquiry, is 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).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.
As discussed above, the skilled artisan cannot envision the detailed genus of “all the variants within insulin A-chain polypeptide and B-chain polypeptide recited in claim 9” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 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.
Therefore, only an insulin dimer wherein each dimer comprises an A-chain polypeptide and a B-chain polypeptide, wherein the A-chain polypeptide comprises amino acid sequence of SEQ ID NO: 1, 7, 10; and the B-chain polypeptide comprises amino acid sequence of SEQ ID NO:2, 6-9, 11 or 12, but not the full breadth of the claim 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).
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.
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.
Claim(s) 1-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (IDS, US 2019/0177393) in view of Schuttler et al. (IDS, Physiol. Chem1982, 363: 317-330).
The instantly claimed invention is broadly drawn to a composition comprising insulin dimer comprising: two insulin molecules dimerized by covalently linking the α-amino groups of the A1 residue of each insulin via a linker moiety, wherein the linker moiety is selected from the group consisting Linker 1-46 (claims 1,8, 12-15), wherein each of the amines of the B-29 lysine or B-28and the N-terminal amino acids of each of the B-chain of the two insulins optionally and independently are conjugated with a capping group (claim 2), wherein the capping group comprises acyl moieties bearing carbamates, PEG-containing chains, sugar-containing groups, carboxylic acid containing groups, amines, amides, hydroxyls, phosphonate groups. and heterocycles, or a mixture thereof (claim 3), wherein the capping group is a linear or branch C1-6 alkyl or has the general formula RC(O)-, where R is: a) a peptide. b) PEG, c) linear or branched C1-6 alkyl chain, d) R'NH-, or e) R'O-, wherein R' is H (when R is R'NH-), peptide, PEG, or linear or branched alkyl chain, and wherein each said peptide, PEG and linear or branched alkyl may be unsubstituted or substituted with 1 to 3 groups selected from amino-, phosphono-, hydroxy-, carboxylic acid, amino acid, PEG, and saccharides (claim 4), wherein the capping group is selected from Capping Group is 13 (claim 5-6), wherein each A-chain polypeptide independently comprises the amino acid sequence GIVEQCCTSICSLYQLENYCN (SEQ ID NO: 1) and each B chain independently comprises amino acid sequence FVNQHLCGSH LVEALYLVCGERGFFYTPKT (SEQ ID NO: 2), FVNQHLCGSHLVEALYLVCGERGFFYTPK (SEQ ID: 11), or FVNQHLCGSHLVEALYLVCGERGFFYTPR (SEQ ID NO: 12 (claims 8-12).
Lin et al. teach an insulin dimer comprising: a first B29 Lys of a first insulin heterodimer molecule having a first A-chain polypeptide and first B-chain polypeptide and a second B29 Lys of a second insulin heterodimer having a second A-chain polypeptide and second B-chain polypeptide conjugated together by a bifunctional linker selected from the group consisting Linker 1, Linker 2, Linker 3, Linker 4, Linker 5, Linker 6, Linker 7, Linker 8, Linker 9, Linker 10, Linker 11, Linker 12, Linker 13, Linker 14, Linker 15, and Linker 16, wherein at least one of the B-chain polypeptides is conjugated at its N-terminal amino acid to a capping group, or at least one of the N-terminal amino acids of the first insulin heterodimer molecule are conjugated to a capping group or at least one of N-terminal amino acids of the first insulin heterodimer and/or second insulin heterodimer are conjugated to a capping group (substituent group) for treating Type I and Type II diabetes and many linkers that connects insulin heterodimers, at least 65 linkers (see paragraph [0003], [0008-0009], FIG. 1-6). Regarding claims 2-5,13, they teach substitution groups selected from amino-, phosphono-, hydroxy-, carboxylic acid, amino acid, PEG, and saccharides (claim 2,11, 12), wherein the capping group is a) dimethyl, b) isobutyl, or c) RC(O)- which is selected from acetyl, phenylacetyl, methoxy acetyl, 2- (carboxymethoxy)acetyl, 2-[bis(carboxymethylamino)]acetyl, carbamoyl, N-alkyl carbamoyl, glutaryl, trifluoroacetyl, glycyl, aminoethylglucose (AEG), AEG-C6, PEGI, PEG2, PEG3, PEG4, PEG5, PEG8, PEG24, and alkoxycarbonyl (see paragraph [0010-0011]). They teach at least 86 dimers that can be selected for treating diabetes (see paragraph [0019]). The connecting linkers are presented in Table of linkers from pg. 7-24 and Linking moieties at pg. 25-35. Regarding claim 16, they teach insulin dimers from pg. 38-68. The insulin dimers are connected at BLys 29 of one heterodimer to BLys of the second insulin heterodimer (see compound 34). Regarding claim 17, they teach to include pharmaceutical carriers (see paragraph [0043]). Regarding claim 18, they teach that the insulin dimer can comprise a glucagon-like protein 1 (GLP-1) receptor agonist (see paragraph [0023]). Lin et al do not teach linking insulin α-amino groups of the A1 residue of each insulin via a linking moiety.
Schuttler et al. teaches insulin conjugates wherein insulin dimers is connected by A1-A’1, B1-B’1, B29-B’29, A1-B’1, A1-B’29 and B’29 (see Fig. 1C).
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Thus, Schuttler et al teaches all the combination of insulin dimer including one being instantly claimed in claim 1.Schuttler et al. teach motivation and guidance to using all interesting insulin derivatives (see pg. 329, col. 1). Additionally, the linkers and capping agents are taught by Lin et al.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a combination of linking A1 amino acid of one of the dimer to A’1 of the second dimer as taught by Schuttler et al using a linker as taught by Lin et al. It would also have been obvious to cap alpha-amino acid moiety as B1, B’1 or amino group of Lys29 to protect them during or even after so they would not be available for cross linking as taught by Lin et al. Additionally, one would have been motivated to do so because Schuttler et al teach insulin dimer can be prepared in 6 different combinations including one being instantly claimed (A1-A’1) combination. Further, one would have a reasonable expectation of success in preparing an insulin dimer combination as taught by Schuttler et al. and by using a linker and a capping agent as taught by Lin et al. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the references.
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.
Claim 1-18 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821 in view of Schuttler et al. (IDS, Physiol. Chem1982, 363: 317-330). Claims 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821 teach a composition comprising insulin dimer comprising: two insulin molecules dimerized by covalently linking the amino groups of the LysB29 of one insulin molecule with B29 Lys residue of second insulin molecule via a linker moiety, wherein the linker moiety is selected from the group consisting Linker 1-46 , wherein each of the amines of the B-29 lysine and the N-terminal amino acids of each of the B-chain of the two insulins optionally and independently are conjugated with a capping group (claim 2), wherein the capping group comprises acyl moieties bearing carbamates, PEG-containing chains, sugar-containing groups, carboxylic acid containing groups, amines, amides, hydroxyls, phosphonate groups. and heterocycles, or a mixture thereof (claim 3), wherein the capping group is a linear or branch C1-6 alkyl or has the general formula RC(O)-, where R is: a) a peptide. b) PEG, c) linear or branched C1-6 alkyl chain, d) R'NH-, or e) R'O-, wherein R' is H (when R is R'NH-), peptide, PEG, or linear or branched alkyl chain, and wherein each said peptide, PEG and linear or branched alkyl may be unsubstituted or substituted with 1 to 3 groups selected from amino-, phosphono-, hydroxy-, carboxylic acid, amino acid, PEG, and saccharides (claim 4), wherein the capping group is selected from Capping Group is 13 (claim 5-6), wherein each A-chain polypeptide independently comprises the amino acid sequence GIVEQCCTSICSLYQLENYCN (SEQ ID NO: 1) and each B chain independently comprises amino acid sequence FVNQHLCGSH LVEALYLVCGERGFFYTPKT (SEQ ID NO: 2), FVNQHLCGSHLVEALYLVCGERGFFYTPK (SEQ ID: 11), or FVNQHLCGSHLVEALYLVCGERGFFYTPR (SEQ ID NO: 12 (claims 8-12) are taught by claims 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821. However, claims 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821 do not teach to conjugate amino groups of A1 to A’1 using a linker.
Schuttler et al. teaches insulin conjugates wherein insulin dimers is connected by A1-A’1, B1-B’1, B29-B’29, A1-B’1, A1-B’29 and B’29 (see Fig. 1C).
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Thus, Schuttler et al teaches all the combination of insulin dimer including one being instantly claimed in claim 1.Schuttler et al. teach motivation and guidance to using all interesting insulin derivatives (see pg. 329, col. 1). Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to use a combination of linking A1 amino acid of one of the dimer to A’1 of the second dimer as taught by Schuttler et al using a linker as taught by Claims 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821. Additionally, one would have been motivated to do so because Schuttler et al teach insulin dimer can be prepared in 6 different combinations including one being instantly claimed (A1-A’1) combination. Further, one would have a reasonable expectation of success in preparing an insulin dimer combination as taught by Schuttler et al. and by using a linker and a capping agent as taught by 1, 6, 8-11, 14-16 and 19-20 of copending Application No. 18/041,821. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the references.
This is a provisional nonstatutory double patenting rejection.
Claim 1-18 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815 in view of Schuttler et al. (IDS, Physiol. Chem1982, 363: 317-330). Claims 1, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815 teach a composition comprising insulin dimer comprising: two insulin molecules dimerized by covalently linking the amino groups of the LysB29 of one insulin molecule with A1G residue of second insulin molecule via a linker moiety, wherein the linker moiety is selected from the group consisting Linker 1-46 , wherein each of the amines of the B-29 lysine and the N-terminal amino acids of each of the B-chain of the two insulins optionally and independently are conjugated with a capping group (claim 2), wherein the capping group comprises acyl moieties bearing carbamates, PEG-containing chains, sugar-containing groups, carboxylic acid containing groups, amines, amides, hydroxyls, phosphonate groups. and heterocycles, or a mixture thereof (claim 3), wherein the capping group is a linear or branch C1-6 alkyl or has the general formula RC(O)-, where R is: a) a peptide. b) PEG, c) linear or branched C1-6 alkyl chain, d) R'NH-, or e) R'O-, wherein R' is H (when R is R'NH-), peptide, PEG, or linear or branched alkyl chain, and wherein each said peptide, PEG and linear or branched alkyl may be unsubstituted or substituted with 1 to 3 groups selected from amino-, phosphono-, hydroxy-, carboxylic acid, amino acid, PEG, and saccharides (claim 4), wherein the capping group is selected from Capping Group is 13 (claim 5-6), wherein each A-chain polypeptide independently comprises the amino acid sequence GIVEQCCTSICSLYQLENYCN (SEQ ID NO: 1) and each B chain independently comprises amino acid sequence FVNQHLCGSH LVEALYLVCGERGFFYTPKT (SEQ ID NO: 2), FVNQHLCGSHLVEALYLVCGERGFFYTPK (SEQ ID: 11), or FVNQHLCGSHLVEALYLVCGERGFFYTPR (SEQ ID NO: 12 (claims 8-12) are taught by Dimers 1, 2,8 and 9; and 1, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815. However, claims 1, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815 do not teach to conjugate amino groups of A1 to A’1 using a linker.
Schuttler et al. teaches insulin conjugates wherein insulin dimers is connected by A1-A’1, B1-B’1, B29-B’29, A1-B’1, A1-B’29 and B’29 (see Fig. 1C).
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Thus, Schuttler et al teaches all the combination of insulin dimer including one being instantly claimed in claim 1.Schuttler et al. teach motivation and guidance to using all interesting insulin derivatives (see pg. 329, col. 1). Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to use a combination of linking A1 amino acid of one of the dimer to A’1 of the second dimer as taught by Schuttler et al using a linker as taught by Claims 11, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815. Additionally, one would have been motivated to do so because Schuttler et al teach insulin dimer can be prepared in 6 different combinations including one being instantly claimed (A1-A’1) combination. Further, one would have a reasonable expectation of success in preparing an insulin dimer combination as taught by Schuttler et al. and by using a linker and a capping agent as taught by claims 1, 6, 9-11, 15-17 and 20-22 of copending Application No. 18/041,815. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the references.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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