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 .
Detailed Action
Claims 1, 10-15, 17, 20-21, 24-26, 28-32 are pending in the instant application.
Election/Restrictions
Applicant elected with traverse Group 1 (claims 1-30) drawn to a peptide and with traverse SEQ ID NO:700 from List I in the response filed July 17, 2026. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)).
The restriction is deemed proper and is made FINAL in this office action. Claims 21, 26, 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected
invention/species, there being no allowable generic or linking claim.
Claims 1, 10-15, 17, 20, 24-26, 28-30, 32 are examined on the merits of this office action.
Claim Rejections - 35 USC § 112
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.
Claim 14 is 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.
Claim 13 requires A linker to comprise 1 to 4 (2-[2-(2-amino ethoxy)-ethoxy]-acetyl) moieties, whereas claim 14 recites that b may be 0, thereby encompassing a linker having none of the moieties required by claim 13. The limitation broadens the scope of claim 13 and thus, claim 14 does not further limit.
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 § 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, 10-15, 17, 20, 24-25, 28-30, 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abraham (WO2021126695 A1, cited in Applicant’s IDS) in view of Abraham* (US20200024322), Agoram (WO2014091316) and Bednarek (WO2015022420).
Abraham teaches of compounds comprising wherein X1 is Y, X2 is Aib, X3 is Gln, X4 is Gly, X5 is T, X6 is aMeF(2F), X7 is T, X8 is S, X8 is D, X10 is 4Pal, X11 is Ser, X12 is I, X13 is aMeL, X14 is L, X15 is Asp, X16 is Orn, X17 is Lys (see claims1, 3), X18 is Ala, X19 is Gln, X20 is 4Pal, X21 is Ala, X22 is Phe, X23 is Ile, X24 is D-glu, X25 is aMeY, X26 is Leu, X27 is Leu, X28 is Glu, X29 is Gly, X30 is Gly, X31 is Pro, X32 is Ser, X33 is Ser, X34 is Gly, X35 is Glu, X36 is Pro, X37 Pro, X38 is Pro, X39 is Ser, X40-41 are absent.
Abraham is silent to wherein X11 and X20 are a-Methylated amino acids, X21 is Glu, X27 is Val, X35 is Ala, and X40-41 are GS.
Abraham does teach that “In addition, the above-described effects of the foregoing lists of modifications are not exclusive, as many of these modifications also have other effects important to the characteristics of the compounds described herein, as described below. [0053] The amino acid sequences of incretin analogs herein incorporate naturally occurring (standard) amino acids, typically depicted herein using one letter codes (e.g., L = leucine; K = lysine), as well as non-standard and/or α-methyl substituted residues of standard amino acids (e.g., αMeL, αMeK, αMeF, αMeF(2F) and αMeY, and certain other non-standard amino acids, such as 4Pal, Aib, Iva, O and D-glutamic acid (e))”(see paragraphs 0053-0054).
Abraham* teaches of GIP/GLP1 agonists wherein X35 is alanine (see claims 1, 4-5), Abraham additionally teaches wherein X11 can be aMeS (see claim 1). Abraham* additionally teaches wherein X21 can be Glu (see claims 1 and 4).
Agoram teaches Glucagon/GLP1 agonists wherein the corresponding X27 is Valine (see claim 1) which is conservative amino acid of Leucine which is taught by Abraham. Agoram teaches that the agonists can be fused to heterologous moieties to increase stability and half life (see paragraph 0033).
Bednarek teaches of GIP/GLP1 agonists with overlapping similarity in the sequences for treatment of diabetes (see abstract, see also paragraph 0082). Bednarek teaches “GIP/GLP-1 agonist peptides as described above can be fused to one or more additional heterologous polypeptide domains. Such additional polypeptide regions can facilitate, e.g., activity, efficacy, stability, or in vivo half-life. For example, a heterologous polypeptide domain can comprise a linker, a hinge, an Fc domain, or a combination thereof. [0096] Linkers used in various GIP/GLP-1 agonist polypeptides provided herein can facilitate formation of a desired structure. In some aspects, a polypeptide linker can comprise 1-50 amino acids, 1-25 amino acids, 25-50 amino acids, or 30-50 amino acids. Generally longer linkers correlate with higher activity (more flexible), but also decreased stability as the peptide becomes more exposed. Linkers can comprise, e.g., (Gly-Ser)n…” (see paragraph 0096). Bednarek additionally teaches wherein X21 can be Glu (see claim 1), X35 can be Ala (see Table 1), X27 can be Val (see Table 1, claim 1).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modify Abraham's GIP/GLP 1 agonist according to the teachings of Abraham*, Agoram, and Bednarek because the references are directed to structurally and functionally related incretin receptor agonist peptides and identify particular amino acid alternatives at corresponding positions of such peptides. A skilled artisan seeking to obtain additional GIP/GLP1 agonists would therefore have had reason to employ the residue selections already demonstrated by the art to be suitable in closely related agonist scaffolds including alpha methylated serine at X11, glu at X21, Val at X27, and Ala at X35. Such modification would have amounted to the application of known peptide design alternatives to a known increment agonist according to their established use yielding no more than the predictable result of another structurally related incretin agonist. In particular where the prior art identified A finite set of residue alternatives at the corresponding positions and demonstrated their use in closely related dual agonist selection of those known alternatives and optimizing Abraham's agonists would have been within the ordinary skill of the artisan. See KSR INTL Co. V. Teleflex inc., 550 US 398, 417-421 (2007) (MPEP2143).
It would have been further obvious to substitute Val for Abraham's Leu at 27 because Agoram and Bednarek especially teach Val at the corresponding position in related incretin agonists and Val represents a conservative substitution for the hydrophobic leu residue. Thus, the prior art provided both a reason to make the particular substitution and evidence that the substitution would be compatible with incretin agonist activity.
The person of ordinary skill would have had a reasonable expectation of success in making the modifications because Abraham, Abraham*, Agoram in Bednarek concern closely related incretin agonist peptides and demonstrate that the identified residues alternatives are tolerated at the corresponding positions while maintaining the desired function.
With respect to the terminal GS residues X40-X41, Bednarek’s teaches the GIP/GLP one agonist peptides may be fused to additional heterologous moieties or peptide domains to further improve properties such as activity efficacy stability and in vivo half-life for treatment of diabetes. Bednarek further teaches the use of peptide linkers for such fusion constructs including linkers comprising GS residues. A person of ordinary skill in the art would have been motivated to modify the C terminal end of Abraham's GIP/GLP1 agonist to include a gs linker extension to provide a suitable flexible attachment region for fusion of the agonist to a heterologous moiety as taught by Bednarek for the purpose of further improving stability and or in vivo half-life (both of which are beneficial in treating diabetic patients). Such modification constitutes the application of a known technique use of a GS containing linker to a similar GIP/GLP1 agonist for the same recognized purpose (treating patients with diabetes) and would have yielded predictable results. A person of ordinary skill would have had a reasonable expectation of success because Bednarek expressly teaches both the use of such fusion constructs in GIP/GLP1 agonist peptides and GS containing linkers for facilitating such constructs.
The combined teachings of Abraham, Abraham*, Agoram and Bednarek render obvious the peptide agonist of claim 1 and instant SEQ ID NO:700 (relevant to claims 17, 20 and 32).
Regarding claim 10, Abraham teaches wherein X17 is Lysine and can be conjugated to a C16-C22 fatty acid via a linker (see claims 1-4).
Regarding claim 11, Abraham teaches wherein the linker has four amino acids (see claim 5).
Regarding claims 12-15, Abraham teaches herein X17 is K chemically modified through conjugation to an epsilon-amino group of a K side-chain with the following structure: (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)a-(γE)b-CO-(CH2)c-CO2H, wherein a is 0, 1 or 2; b is 1 or 2; and c is an integer between 16 to 20 (see claims 9-14).
Regarding claim 24, Abraham teaches wherein the c-terminal is amidated (see claim 1).
Regarding claim 25, Abraham teaches wherein the pharmaceutically acceptable salt is trifluroacetate salts, acetate salts or hydrochloride salts (see paragraph 0016).
Regarding claims 28 and 30,Abraham teaches pharmaceutical formulations with carriers and wherein the formulation is formulated for subcutaneous administration (see paragraphs 0016, claim 33). Regarding claim 29, Abraham* teaches oral administration (see abstract). It would have been obvious to administer Abraham's GIP/GLP1 agonist orally as taught by Abraham* as an alternative to Abraham's subcutaneous administration because both were known administration routes for GIP/GLP1 agonist with a reasonable expectation of successful administration and therapeutic effectiveness.
Claim 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abraham (WO2021126695 A1, cited in Applicant’s IDS) in view of Abraham* (US20200024322), Agoram (WO2014091316) and Bednarek (WO2015022420) as applied to claims 1, 10-15, 17, 20, 24-25, 28-30, 32 above, in further view of Zhong (US2020028342).
The combined references above are silent to wherein one or more hydrogen atoms are replaced by deuterium.
However, Zhong teaches GLP1R agonists With incorporation of deuterium. Zhong specifically teaches “Substitution with heavier isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements” (see paragraph 0191).
It would have been obvious before the effective filing date of the claim invention to incorporate deuterium into the peptide agonist of Abraham Abraham*, Agoram and Bednarek as taught by Zhong. One of ordinary skill in the art would have been motivated to do so to improve metabolic stability and or increase half life. There is a reasonable expectation of success given that Zhong teaches deuterium incorporation enter GLP1 agonists for therapeutic purposes.
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, 10-15, 17, 20, 24-26, 28-30, 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-87 of Co-pending AN19/279475 in view of Abraham (WO2021126695 A1, cited in Applicant’s IDS), Abraham* (US20200024322) and Zhong (US2020028342).
The instant application claims a polypeptide comprising X1-X39 wherein X1 is Y, X2 is Aib, X4 is G, X6 is aMeF(2F), X10 is 4-Pal, X11 is aMeS, X12 is I, X13 is aMeL, X15 is D, X16 is Orn, X17 is Lys, X19 is Gln, X20 is aMe-4-Pal, X21 is E, X23 is I, X24 D-Glu, X25 is aMeY, X27 is V, X28 is Glu, X29 is Gly, X31 is Pro, X32 is Ser, X34 is Gly, X35 is Ala, X37 is Pro, X39 is Ser, X40 is Gly, X41 is Ser. The instant application claims fatty acid conjugation to X17 Lys (claim 10); linker (claims 11-15); SEQ ID NO:700 (claims 17, 20, 32); salt thereof (claim 25); c terminal amidation (claim 24); pharmaceutical formulations (oral and subcutaneous)(see claims 28-30).
Co-pending AN19/279475 claims a compound comprising SEQ ID Nos:217 and 30 which comprise instant SEQ ID NO:700 thus meeting the limitations of the instant claims (see claims 1, 18, 20). Co-pending AN19/279475 further claims Fatty acid conjugation at lys at position 17 via the same linkers of the instant claims (see claims 40-43); pharmaceutical formulations thereof (claims 85-86) and salts thereof (claim 1). Co-pending AN19/279475 does not claim oral or parenteral administration (subcutaneous) or deuterium incorporation. However, Abraham teaches pharmaceutical formulations with carriers and wherein the formulation is formulated for subcutaneous administration (see paragraphs 0016, claim 33). Abraham* teaches oral administration (see abstract). It would have been obvious to administer Co-pending AN19/279475 GIP/GLP1 agonist orally as taught by Abraham* or Abraham's subcutaneous administration because both were known administration routes for GIP/GLP1 agonist with a reasonable expectation of successful administration and therapeutic effectiveness.
Zhong teaches GLP1R agonists With incorporation of deuterium. Zhong specifically teaches “Substitution with heavier isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements” (see paragraph 0191).
It would have been obvious before the effective filing date of the claim invention to incorporate deuterium into the peptide agonist of AN19/279475 as taught by Zhong. One of ordinary skill in the art would have been motivated to do so to improve metabolic stability and or increase half life. There is a reasonable expectation of success given that Zhong teaches deuterium incorporation enter GLP1 agonists for therapeutic purposes.
Claims 1, 10-15, 17, 20, 24-26, 28-30, 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-54, 56-61, 68-102, 104 of Co-pending AN19/651407 in view of Abraham (WO2021126695 A1, cited in Applicant’s IDS) Abraham* (US20200024322) and Zhong (US2020028342).
The instant application claims a polypeptide comprising X1-X39 wherein X1 is Y, X2 is Aib, X4 is G, X6 is aMeF(2F), X10 is 4-Pal, X11 is aMeS, X12 is I, X13 is aMeL, X15 is D, X16 is Orn, X17 is Lys, X19 is Gln, X20 is aMe-4-Pal, X21 is E, X23 is I, X24 D-Glu, X25 is aMeY, X27 is V, X28 is Glu, X29 is Gly, X31 is Pro, X32 is Ser, X34 is Gly, X35 is Ala, X37 is Pro, X39 is Ser, X40 is Gly, X41 is Ser. The instant application claims fatty acid conjugation to X17 Lys (claim 10); linker (claims 11-15); SEQ ID NO:700 (claims 17, 20, 32); salt thereof (claim 25); c terminal amidation (claim 24); pharmaceutical formulations (oral and subcutaneous)(see claims 28-30).
Co-pending AN19/651407 claims a compound comprising SEQ ID Nos: 30 which comprise instant SEQ ID NO:700 thus meeting the limitations of the instant claims (see claims 45, 47,51). Co-pending AN19/651407 further claims Fatty acid conjugation at lys at position 17 via the same linkers of the instant claims (see claims 53, 57); pharmaceutical formulations thereof (claims 101-102) and salts thereof (claim 1). Co-pending AN19/651407 does not claim oral or parenteral administration (subcutaneous) or deuterium incoporation. However, Abraham teaches pharmaceutical formulations with carriers and wherein the formulation is formulated for subcutaneous administration (see paragraphs 0016, claim 33). Abraham* teaches oral administration (see abstract). It would have been obvious to administer Co-pending AN19/651407 GIP/GLP1 agonist orally as taught by Abraham* or Abraham's subcutaneous administration because both were known administration routes for GIP/GLP1 agonist with a reasonable expectation of successful administration and therapeutic effectiveness.
Zhong teaches GLP1R agonists With incorporation of deuterium. Zhong specifically teaches “Substitution with heavier isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements” (see paragraph 0191).
It would have been obvious before the effective filing date of the claim invention to incorporate deuterium into the peptide agonist of AN19/651407 as taught by Zhong. One of ordinary skill in the art would have been motivated to do so to improve metabolic stability and or increase half life. There is a reasonable expectation of success given that Zhong teaches deuterium incorporation enter GLP1 agonists for therapeutic purposes.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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