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 .
Status of the Application
The claims of 19 November 2023 are entered.
Claims 1-21 are pending and are being examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Claim Objections
Claim 17 objected to because of the following informalities: the claim recites “N-linked glycan” followed by “(N-linked glycan)”. The N-linked glycan in parenthesis is redundant. Appropriate correction is required.
Claim Interpretation
Claim 1 recites within the preamble the language “for preventing or treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH)”. Per MPEP 2111.02, preamble statements reciting intended use when the body of the claim fully and intrinsically sets forth all of the limitations of the claimed invention are not considered a limitation and are not of significance to claim construction. In this case, the body of the claim sets forth all limitations regarding the GDF-15 variant and the preamble is only reciting an intended use rather than any distinct definition of any of the claimed invention’s limitations. The preamble statement is therefore not considered to be a limitation for the purposes of prior art.
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 specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See p.22.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, 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 § 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.
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating NAFLD or NASH, does not reasonably provide enablement for preventing NAFLD or NASH. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict-ability of the art, and (8) the breadth of the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Nature of the Invention
The claims are drawn to a pharmaceutical composition either comprising a GDF15 variant, long-acting GDF15 fusion protein, or a long-acting GDF15 fusion protein dimer, or alternatively a complex comprising a GDF15 variant and an IgG Fc of formula IgG Fc – (L)m – N-terminal extension domain – core domain. The claims include an intended use for treating or preventing NAFLD or NASH.
Breadth of the Claims
The claims are broad concerning the composition, but narrower with respect to the intended use.
State of the Prior Art
Mahady S and George J (J Hepatology 4:P774-P775, published October 2018) indicate that diagnostic tools for predicting NAFLD and NASH are limited, with ultrasound being of low sensitivity for mild forms of the disease, and liver enzymes not always correlating with disease state in 50-80% of cases (see e.g. 1st paragraph).
The NIDDK (https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/treatment, published 2021) indicates that there are no treatments for NAFLD or NASH, let alone preventative compounds.
Certain lifestyle changes including physical activity and a Mediterranean diet can reduce liver fat (see e.g. Trovato et al. (Hepatobiliary Surg Nutr. 8:167-169, published April 2019).
Relative Skill of those in the Art
The relative skill of those in the art is high.
Predictability or Unpredictability of the Art
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
There similarly is no reliable prediction as to whether a patient will or will not develop NAFLD or NASH.
Amount of Direction or Guidance Given
The specification offers no real guidance on prevention in terms of a specific definition that might limit the scope and offer the skilled artisan an indication of what is encompassed by the terminology.
Presence/Absence of Working Examples
No working examples are present where the GDF15 variants are demonstrated to prevent NAFLD or NASH.
Quantity of Experimentation Necessary
Since there are no approved treatments for NAFLD or NASH per the NIDDK, the effort to demonstrate that the GDF15 variants as claimed are preventative is left entirely on the part of the skilled artisan. There is no particular guidance on what prevention encompasses, so the artisan must assume that the ordinary definition implying complete non-occurrence of NAFLD or NASH must occur. As indicated above the art indicates that prediction of NAFLD or NASH can be difficult when bloodwork can appear normal in 50-80% of cases. All of these issues do not even take into account the breadth associated with the claimed GDF15 variants.
Collectively, the factors point towards the level of experimentation required to be undue, since the skilled artisan is left to handle all aspects of verifying that the GDF15 variants prevent NAFLD and NASH across the breadth as claimed, as well as determine the amounts that are necessary to prevent both conditions.
In view of the Wands factors as discussed above, it is the Examiner’s opinion that the claims are not fully enabled and one of skill in the art would have to engage in undue experimentation to practice the invention as claimed herein, without a reasonable assurance of success.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Lim et al. (WO 2021/107603 A2, published 3 June 2021, filed 25 November 2020, priority to 26 November 2019, hereafter referred to as ‘603).
The applied reference has a common Applicant and Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
As noted above, the intended use of the claimed composition as found in the preamble is not considered to be of significance to claim construction.
The ‘603 application discloses a GDF variant comprising a N-terminal extension domain followed by a core domain, with the N-terminal extension domain represented by any of SEQ ID NO: 3-5 and the core domain being represented by SEQ ID NO: 20 or a variant at positions 15, 50, 58, 97, and combinations thereof (see e.g. claim 1). ‘603 also discloses a composition with this GDF variant (see e.g. claim 22). This anticipates claim 1.
With respect to claim 2, the ‘603 application discloses the same mutations to the core domain (see e.g. claim 2).
With respect to claim 3, the ‘603 application discloses the same core domain sequences of SEQ ID NOs: 6-19 (see e.g. claim 3).
With respect to claim 4, the ‘603 application discloses the same combination of SEQ ID NO: 3 with SEQ ID NOs: 8, 9, or 20 (see e.g. claim 4).
With respect to claim 5, the ‘603 application discloses the same combination of SEQ ID NO: 4 with SEQ ID NOs: 8, 9, or 20 (see e.g. claim 5).
With respect to claim 6, the ‘603 application discloses the same combination of SEQ ID NO: 5 with SEQ ID NOs: 6-19 (see e.g. claim 6).
With respect to claim 7, the ‘603 application discloses SEQ ID NOs: 21-39 (see e.g. claim 7).
With respect to claim 8, the ‘603 application discloses fusion to a human IgG Fc or a variant (see e.g. claim 8).
With respect to claim 9, the ‘603 application discloses a dimer of the long-active GDF fusion protein (see e.g. claim 18).
With respect to claim 10, the ‘603 application discloses the same IgG Fc (see e.g. claim 9).
With respect to claim 11, the ‘603 application claims the same arrangement (see e.g. claim 10).
With respect to claim 12, the ‘603 application discloses a linker (see e.g. claim 11).
With respect to claim 13, the ‘603 application discloses the same linker (see e.g. claim 12).
With respect to claim 14, the ‘603 application discloses the same linkers (see e.g. claim 13).
With respect to claim 15, the ‘603 application discloses the same first polypeptides (see e.g. claim 14).
With respect to claim 16, the ‘603 application discloses the same second polypeptides (see e.g. claim 15).
With respect to claim 17, the ‘603 application discloses an N-linked glycan (see e.g. claim 16).
With respect to claim 18, the ‘603 application discloses the same GDF15 variant, first polypeptide, and second polypeptide (see e.g. claim 17).
With respect to claim 19, as set forth above ‘603 already discloses a fusion of an IgG Fc of SEQ ID NOs: 42, 44, or 46, a linker of SEQ ID NOs: 48, 92, 93, 94, 95, 96, or 97, and a GDF15 variant of an N-terminal extension and core domain.
With respect to claim 20, as set forth above ‘603 discloses the N-terminal extension – core domain of SEQ ID NOs: 21-39.
With respect to claim 21, ‘603 discloses at least SEQ ID NOs: 49, 65, and 69-91 (see e.g. Table 1). SEQ ID NOs: 50-64, 67, 68, and 98-109 are also found in the sequence disclosure of ‘603.
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 1-21 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-18 and 23-25 of copending Application No. 18/562,322 (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 ‘322 applicant similarly recites an intended use in the preamble of “for preventing or treating diabetes, obesity, dyslipidemia, or metabolic syndrome by administering in combination with a GLP-1 (glucagon-like peptide-1) receptor agonist”. This is treated as an intended use since the body of the claim sets forth all limitations for the pharmaceutical composition, comprising a GDF15 variant, a long-acting GDF15 fusion protein, or a long-acting GDF15 fusion protein dimer as an active ingredient.
Since the intended use of ‘322 and the instant application are not considered claim limitations, the underlying pharmaceutical composition is otherwise identical between claims 1-18 and 23-25 of ‘322 and claims 1-21 of the instant application.
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 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 11-13, 16, 18, 21, 29, and 30 of copending Application No. 17/779,932 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘932 application claims an overlapping GDF15 variant, fusion, and dimer.
As noted above, the instant claims recite an intended use that is not considered to be a claim limitation.
The ‘932 application claims a GDF variant comprising a N-terminal extension domain – core domain of Formula (I) matching Formula (I) as instantly claimed (see e.g. claim 1). The ‘932 application also claims this as a pharmaceutical composition (see e.g. claim 22). This overlaps with claim 1.
With respect to claim 2, the ‘932 application claims an overlapping variant in claim 1.
With respect to claim 3, ‘932 claims SEQ ID NOs: 6-19 (see e.g. claim 3).
With respect to claim 4, ‘932 claims a combination of SEQ ID NO: 3 with SEQ ID NOs: 8, 9, or 20 (see e.g. claim 4).
With respect to claim 5, ‘932 claims a combination of SEQ ID NO: 4 with SEQ ID NOs: 8. 9, or 20 (see e.g. claim 5).
With respect to claim 6, ‘932 claims a combination of SEQ ID NO: 5 with one of SEQ ID NOs: 6-19 (see e.g. claim 6).
With respect to claim 7, ‘932 claims SEQ ID NOs: 21-39 (see e.g. claim 7).
With respect to claims 8, 10, 11, 15-16, and 18, ‘932 claims a long-acting GDF15 fusion protein where an IgG Fc of first polypeptide selected from SEQ ID NOs: 42, 44, and 46 and a second polypeptide of SEQ ID NOs: 43, 45, and 47 are fused via their C-terminus to the N-terminus of the GDF15 variant (see e.g. claim 8).
With respect to claim 9, ‘932 claims a dimer (see e.g. claim 18).
With respect to claims 12-14, ‘932 claims overlapping linkers (see e.g. claims 11-13).
With respect to claim 17, ‘932 claims a N-linked glycan (see e.g. claim 16).
With respect to claim 19, ‘932 claims an overlapping complex (see e.g. claim 29).
With respect to claim 20, ‘932 claims the SEQ ID NOs: 21-39 (see e.g. claim 30).
With respect to claim 21, ‘932 claims SEQ ID NOs: 51-91 and 98-109 (see e.g. claim 21).
Please note that while ‘932 does not claim any pharmaceutical compositions beyond that of claim 1, it would have been equally obvious to one of ordinary skill in the art to have applied the pharmaceutical composition of claim 22 to any other claims of ‘932 in order to prepare other pharmaceutical compositions. The rationale comes from the desire to prepare compounds ready for pharmaceutical administration in order to treat patients. There would have been a reasonable expectation of success because ‘932 already claims the base GDF15 variant as a pharmaceutical and one of ordinary skill in the art is well acquainted with preparation of peptides as pharmaceutical compositions. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
Prosecution Insights