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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 80 and 99-111 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Revell et al. (WO 2015/086686 A2, hereafter “WO 2015/086686 A2”).
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGTFTSDVSS-(a-MeF)-LEGQAAKEFIAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is T, X6 is F, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is F, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 9, Table 2, page 41).
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGT-(a-MeF)-TSDVSS-(a-MeF)-LEGQAAKE-(a-MeF)-IAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is T, X6 is a-MeF, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is a-MeF, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 29, Table 2, page 43).
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGS-(a-MeF)-TSDVSS-(a-MeF)-LEGQAAKE-(a-MeF)-IAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is S, X6 is a-MeF, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is a-MeF, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 34, Table 2, page 44).
These peptides are species in the claimed genus and therefore anticipate claim 80.
With respect to claims 99-102, WO 2015/086686 A2 teaches that the peptides have agonist activity to the human glucagon, GLP-1, and GIP receptors (Table 2).
With respect to claims 103 and 105-108, WO 2015/086686 A2 teaches that the peptides have increased proteolytic stability relative to the natural ligand of the GLP-1R and/or GCGR, wherein the proteases are neprilysin, pepsin, and simulated gastric fluid (Table 2; Figures 2-14). The claimed functions are inherent to the prior art peptides, which meet all of the structural limitations of the claims.
With respect to claim 104, WO 2015/086686 A2 teaches that the peptides are isolated ([0127]).
With respect to claims 109-111, WO 2015/086686 A2 teaches pharmaceutical compositions comprising the peptides and pharmaceutically-acceptable carriers for liquid and solid forms ([0109]-[0112]).
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.
Claims 85, 87, 88 and 90-98 are rejected under 35 U.S.C. 103 as being unpatentable over Revell et al. (WO 2015/086686 A2, hereafter “WO 2015/086686 A2”), as applied to claims 80 and 99-111 above, in view of Revell et al. (US 2020/0079833 A1, hereafter “US 2020/0079833 A1”).
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Determining the scope and contents of the prior art.
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGTFTSDVSS-(a-MeF)-LEGQAAKEFIAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is T, X6 is F, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is F, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 9, Table 2, page 41).
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGT-(a-MeF)-TSDVSS-(a-MeF)-LEGQAAKE-(a-MeF)-IAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is T, X6 is a-MeF, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is a-MeF, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 29, Table 2, page 43).
WO 2015/086686 A2 teaches the peptide:
H-Aib-EGS-(a-MeF)-TSDVSS-(a-MeF)-LEGQAAKE-(a-MeF)-IAWLVKGR
which corresponds to a peptide in the genus of instant claim 80 wherein
X2 is Aib, X3 is E, X5 is S, X6 is a-MeF, X10 is V, X12 is S, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X22 is a-MeF, X23 is I, X24 is A, X25 is W, X26 is L, X27 is V, X28 is K, X29 is G, X30 is R, X31 is not present, and Z is an acid (SEQ ID NO: 34, Table 2, page 44).
Ascertaining the differences between the prior art and the claims at issue.
WO 2015/086686 A2 teaches that the peptides can further comprise modification by lipidation, including carboxyl- or amino- terminal lipidation, or main-chain lipidation to improve stability, and that methods of preparing synthetic peptides with such a lipidation are known in the art ([0078]). However, WO 2015/086686 A2 does not teach that the peptides are lipidated at the lysine at position 20.
Resolving the level of ordinary skill in the pertinent art.
US 2020/0079833 A1 teaches that the protease stability of GLP-1 peptides can be improved by a combination of alpha-methyl functionalized amino acids at positions 2, 6, 11, 12, 13, 20, 22, 24, 25, and/or 28, and acylation/lipidation at positions 12, 20, and 24 ([0009]; Figure 1; Figures 8-10).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The specification does not provide a comparison between the peptides disclosed in the prior art of WO 2015/086686 A2 and the derivatives wherein lysine 20 is lipidated. Therefore, there is no evidence of unexpected results on record.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to lipidate lysine 20 in the peptides taught WO 2015/086686 A2. The rationale for obviousness is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP § 2143.01(G)). The relevant findings for this rationale are as follows.
(1) There was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings. In the instant case, WO 2015/086686 A2 teaches GLP-1/glucagon peptides comprising modifications designed to improve proteolytic stability. The modifications include the incorporation of alpha-methyl amino acids at positions 2, 6, 13, and 22 (Figure 1, Table 2). WO 2015/086686 A2 teaches that the same GLP-1/glucagon peptides comprise a lysine at position 20 (Table 2). In addition, US 2020/0079833 A1 teaches that the protease stability of GLP-1/glucagon peptides can be improved by combining alpha-methyl functionalized amino acids at the same positions used in WO 2015/086686 A2 with lipidation at positions 12, 20, and/or 24 ([0009]). One of ordinary skill in the art would have been motivated to apply the lipidation strategy taught by US 2020/0079833 A1 to the peptides in WO 2015/086686 A2 to further improve proteolytic stability. Therefore, there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings.
(2) There was reasonable expectation of success. One of ordinary skill in the art would predict that lipidation at position 20 would improve the proteolytic stability of the peptides of WO 2015/086686 A2 because these peptides have a lysine at this position that is capable of being lipidated by standard methods in the art and because US 2020/0079833 A1 teaches that lipidation at this position can improve proteolytic stability alone or in combination with the incorporation of alpha-methyl amino acids found in the peptides of WO 2015/086686 A2. Therefore, there was a reasonable expectation of success.
(3) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not provide a comparison between the peptides disclosed in the prior art of WO 2015/086686 A2 and the derivatives wherein lysine 20 is lipidated. Therefore, there is no evidence of unexpected results on record.
The rationale to support a conclusion that the claim would have been obvious is that "a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006).
Therefore, claims 85, 87, 88 and 90 are obvious over the cited art.
Regarding claims 91-93, US 2020/0079833 A1 teaches that the lipid may be a C18 or C18diacid (Figure 1; Figures 8-10).
Regarding claims 94-98, US 2020/0079833 A1 teaches that the lipid may be attached via the claimed linkers (Figure 1; Figures 8-10).
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 80-82 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 40, and 41, respectively of copending Application No. 19/651,155 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
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 80, 81, 82, and 85-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,630,600. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Patented claim 1 recites a peptide comprising the amino acid sequence selected from the group consisting of:
(i) H-Aib-Q-G-T-F-T-S-D-V-S-K-αMePhe-L-D-T-X17-R-A-R-D-F-V-Q-W-L-L-E-Aib-G-acid (SEQ ID NO: 100); wherein X17 is K(O2Oc)-(O2Oc)-γE-C18diacid);
(ii) H-Aib-Q-G-T-F-T-S-D-V-S-K-αMePhe-L-D-T-X17-R-A-R-D-F-V-Q-W-L-L-E-Aib-G-acid (SEQ ID NO: 107); wherein X17 is K(O2Oc)-(O2Oc)-γE-C20diacid);
(iii) H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-X20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 228); wherein X20 is K(ε-(O2Oc)-(O2Oc)-γE-C18diacid); and
(iv) H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-X20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 233); wherein X20 is K(ε-(O2Oc)-(O2Oc)-γE-γE-C20diacid).
These peptides correspond to the formula in instant claim 1 wherein
(i) and (ii) X2 is Aib, X3 is Q, X5 is T, X6 is F, X10 is V, X12 is K, X15 is D, X16 is T, X17 is K, X18 is R, X20 is R, X21 is D, X22 is F, X23 is V, X24 is Q, X25 is W, X26 is L, X27 is L, X28 is E, X29 is Aib, X30 is G, X31 is not present, and Z is an acid; and
(iii) and (iv) X2 is Aib, X3 is H, X5 is S, X6 is αMePhe, X10 is V, X12 is K, X15 is D, X16 is S, X17 is R, X18 is A, X20 is K, X21 is D, X22 is αMePhe, X23 is V, X24 is Q, X25 is Aib, X26 is I, X27 is A, X28 is N, X29 is T, X30 is G, X31 is not present, and Z is an acid.
These peptides are species in the claimed genus and therefore anticipate claim 80.
Regarding claim 81, the peptides (i) and (ii) have X2 is Aib, X12 is K, and X24 is Q.
Regarding claim 82, the peptides (i) and (ii) X16 is T, X17 is K, X27 is L, X28 is E, and X29 is Aib.
Regarding claims 85-90, the peptides (i)-(iv) have either K17 or K20 acylated/lipidated.
Regarding claims 91-93, the peptides (i)-(iv) have either K17 or K20 acylated/lipidated with C18diacid or C20diacid.
Regarding claims 94-98, the peptides (i)-(iv) have either K17 or K20 acylated/lipidated at the epsilon amino group via a linker, wherein the linker is (O2Oc)-(O2Oc)-γE or (O2Oc)-(O2Oc)-γE-γE.
Regarding claims 99-102, patented claims 2-5 require that the peptide binds to the GLP-1 receptor (GLP-1R), binds to the glucagon receptor (GCGR), or binds to both a GLP-1 receptor and a glucagon receptor, wherein the GLP-1R is a human GLP-1R, wherein the GCGR is a human GCGR, and wherein the peptide is an agonist of GLP-1 activity, an agonist of glucagon activity, or an agonist of both GLP-1 and glucagon activity.
Regarding claims 103 and 105-108, patented claims 6 and 8-11 require the same properties regarding stability, respectively.
Regarding claim 104, patented claim 7 requires that the peptide isolated.
Regarding claims 109-111, patented claims 6 and 8-11 require a pharmaceutical composition comprising the peptide, in solid or liquid form.
Claims 85-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-75 of copending Application No. 19/651,155 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims 1, 40, and 41 are identical to instant claims 80-82, respectively.
Reference claims 44-57 and 63-57 recited the same limitations as instant claims 85-111, respectively, in multiple dependent form.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 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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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
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