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 .
Response to Amendment
Claims 1-144 have been cancelled; Claims 145-158 have been newly added as requested in the amendment filed on 19 April 2024. Following the amendment, claims 145-158 are pending in the instant application; and are under examination in the instant office action.
Sequence compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821 (a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825. Specifically, no sequence identification has been provided for the nucleic acid sequences presented in Figures 2A through 2D of the instant specification. In case these sequences are new, Applicant needs to provide a substitute computer readable form (CRF) copy of a "Sequence Listing" which includes all of the sequences that are present in the instant application and encompassed by these rules, a substitute paper copy of that "Sequence Listing", an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 (e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO: ) be made in the specification and claims wherever a reference is made to that sequence. See M.P.E.P. 2422.04.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a continuation of US Application No. 17/918,760 filed 13 October 2022, which is itself a 371 national stage entry of PCT/US2021/027839 filed on 16 April 2021, and claims the benefit of US Provisional Application No. 63/011,491 filed on 17 April 2020.
Claims 145-158 have an effective US filing date of 17 April 2020.
Claim Objections
Claims 145-147 are objected to because of the following informalities: these claims contain abbreviations that are not spelled out upon their first appearance within the claims (ex. IgG, EU, CH2, CH3). Appropriate correction is required.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Specifically, embedded hyperlinks appear in the following locations: page 36, Example 1 reference to Agilent primer design website. Appropriate correction is required.
Additionally, the specification is objected to because it states: “[00015] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.” However, Applicant has filed no corresponding Petition for Color Drawings. Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). Appropriate correction is required.
Information Disclosure Statement
The references in the specification (i.e. paragraphs [0003]; [00066]; [00082]; [00086]; [00091], etc.) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
The term “increasing” in claims 145 and 151 is a relative term which renders the claim indefinite. The term increasing/increases is not defined by these claims, nor does the specification provide a standard for ascertaining the requisite degree. Additionally, there are no method steps in independent claim 145 whereby this increased serum half-life is assessed. Therefore, one of ordinary skill in the art would not be reasonably apprised as to whether or not assessing an increase was required for direct infringement of the invention. Thus, the scope of the invention is indefinite. For purposes of applying prior art, the increased half-life recited by these claims will be interpreted as an inherent property of the feline IgG structure recited in instant claims 145 and 151. This rejection affects the scope of all depending claims.
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 145-148, 151-154 and 157-158 are 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 following art disclosed prior to the filing date of the application teaches antibody sequencing of the antibody repertoire of just 4 domestic cats yields a total number of 1079863 sequences generated for VH for IgG and the authors analysis suggests that a similar expression pattern exists across all cats (Abstract; Steiniger et al., Comparative analysis of the feline immunoglobulin repertoire, Biologicals 46: 81-87, 2017). The VH constant region is a crucial part of the antibody structure, responsible for the antigen-binding specificity and diversity of the antibody. It is located at the tips of the antibody molecule and is composed of parts of the heavy (VH) and light (VL) chains (see diagram below).
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However, the claims do not require any constant region structure other than a single amino acid substitution. Thus, the claims encompass a genus of substituted feline IgG constant regions, the art discloses this genus is vast (1079863 IgG VH sequences in only 4 domestic cats). The specification teaches only one species within the genus encompassed by the claims –an IgG constant domain as set forth in SEQ ID NO:3 further comprising the amino acid substitution of serine with histidine at residue 434. The specification discloses only one species of mutant feline IgG constant domain set forth in SEQ ID NO:2, within the genus of substituted IgGs claimed.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)( i)(A), reduction to drawings MPEP 2163(II)(3)(a) (i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a) (i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The one embodiment disclosed in the specification does not constitute a representative number of species within the recited genus claimed.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics for the genus as a whole, or a representative number of species within the genus claimed, the specification does not provide adequate written description of the claimed genus.
Claims 145-148, 151-154 and 157-158 are rejected for failing to meet the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Claims 145-158 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 a mutant feline IgG constant domain comprising SEQ ID NO:2, does not reasonably provide enablement for : (1) increasing serum half-life by substituting any feline IgG with a histidine amino acid at residue 434 over the wild-type serine residue; (2) feline IgGs having only one CH2 or CH3 domain; and (3) fusion proteins comprising any feline IgG comprising any amino acid at residue 434 (instant claim 158). 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/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be “given their broadest reasonable interpretation consistent with the specification.” See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
As such, the broadest reasonable interpretation of the claimed inventions provide for increased half-life by substituting a histidine amino acid at residue 434 over the wild-type serine. The specification a single mutant IgG constant domain consisting of SEQ ID NO: 2 that demonstrates increased half-life (pg. 38-39, Table 3). Table 4 (pg. 39) of the specification, however, discloses only one S434H substitution in monoclonal antibody 3 (mAb3), provides for the functional requirements of the instant claims - increased half-life. As stated in the rejection above, the art at the time of filing disclosed multiple feline IgGs VH chains were known (Steiniger et al., Comparative analysis of the feline immunoglobulin repertoire, Biologicals 46: 81-87, 2017). Thus, what is enabled by the working examples is narrow in comparison to the breadth of the claims.
It was well-established in the art that FcRn binding affects serum half-life kinetics of antibodies (Andersen et al., J Biol Chem., Vol 289, No. 19: 13492-13502, 2014). The authors teach IgG homeostatic regulation is controlled by a cellular receptor, named the neonatal Fc receptor (FcRn), which rescues IgG from intracellular degradation and thus is responsible for prolonging the half-lives of IgG molecules (pg. 13492, first full paragraph after Abstract). Table 5A of the instant specification, however, discloses not all S434H mutants have increased FcRn binding relative to wild-type.
The Supreme Court in AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), stated: “An antibody’s structure does much to dictate its function…Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody’s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody’s structure and function. Ibid.”
Thus, antibody structure is essential to function and Applicant has actually reduced to practice only one embodiment encompassed by the breadth of the claims – the substituted mutant of SEQ ID NO: 2. Given that the feline IgG constant domain repertoire is vast (again, 1079863 IgG VH sequences in only 4 domestic cats); and given the unpredictability within the art with respect to creating antibodies, then a person having ordinary skill in the art would have to perform further experimentation in order to make multiple substituted IgGs, encompassed by the claims, and then test their serum half-lives, in order to enable the invention commensurate in scope with the breadth of the claims. This amount of experimentation goes beyond what is considered ‘routine’ within the art and constitutes undue further experimentation in order to make and use the invention, as claimed, with a reasonable expectation of success.
Therefore, Claims 145-158 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
Double Patenting
There are no double patenting issues between this application and co-pending application 17/918,860 because the co-pending claims require a substitution at residue 428 and explicitly recites wild-type residues at position 434. Therefore, despite open-ended claim language (“comprising”) in the instant claims, which does not exclude additional substitutions, the co-pending claims exclude substitutions at residue 434.
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 151-158 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-15, 18-20 and 72-73 of copending Application No. 18/266,053 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims comprise a polypeptide comprising a feline IgG substituted at position 434 and depending claims specifically S434H within wild-type sequence as set forth in SEQ ID NO: 3, which is the same as the instant claims. Therefore, the reference claims would anticipate the product claims of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M.
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675