Detailed Office 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 Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 16 June, 2025. Claims 1, 2, and 7-22 are pending in the instant application. Claims 15-22 stand withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 C.F.R. § 1.144). See M.P.E.P. § 821.01.
Claim Objections
Claims 4 and 7-10 are objected to because of the following informalities: the claims reference non-elected subject matter. Applicants are reminded of the original restriction requirement and subsequent election. The claims should be directed toward mAb 8A9F9. Appropriate correction is required.
35 U.S.C. § 112(b)
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 previous rejection of claims 4, 5, and 7-10 under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention, is hereby withdrawn in response to Applicants’ amendment and arguments.
35 U.S.C. § 102
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.
The previous rejection of claims 1, 3, 12, and 13 under 35 U.S.C. § 102(a)(1) as being clearly anticipated by Stettler et al. (2016), is hereby withdrawn in response to Applicants’ amendment and arguments.
Joint Inventors, Common Ownership Presumed
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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.
35 U.S.C. § 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 of this title, 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.
Graham v. Deere
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied 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.
The previous rejection of claims 2, 11, and 14 under 35 U.S.C. § 103 as being unpatentable over Stettler et al. (2016) in view of Flingai et al. (2015), is hereby withdrawn in response to Applicants’ amendment and arguments.
35 U.S.C. § 112(a)
The following is a quotation 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.
Written Description
Claims 1, 2 and 7-14 stand rejected under 35 U.S.C. § 112(a), 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, at the time the application was filed, had possession of the claimed invention. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
The guidelines for determining if patent claims comply with the written description requirement of 35 U.S.C. § 112, first paragraph, include the following: 1) Determining the full claim breadth. 2) Comparing the claim breadth with the scope of support provided by the disclosure. 3) Determining if one skilled in the art would recognize at the time of filing that Applicants were in possession of the claimed invention. The following factors should be considered in making such an assessment: a) Actual reduction to practice. b) Disclosure of structural characteristics (through drawings or chemical formulas). c) Disclosure of relevant identifying characteristics including a complete or partial structure, physical or chemical properties, and functional characteristics coupled with a known or disclosed structural/functional correlation. d) Method of making the claimed invention. e) The level of skill and knowledge in the art. f) Predictability of the art. 4) Consider the aforementioned factors and determine if a representative number of species have been provided to conclude that Applicant was in possession of the claimed invention at the time of filing.
The amended claims are directed toward a nucleic acid molecule encoding one or more synthetic anti-ZIKV envelope (E) protein antibodies wherein said antibodies comprise at least 95% sequence identity to SEQ ID NOS.: 3, 4, 13, 14, and 19, antigen binding fragments thereof. The claims are still directed toward a large genus of antibodies and the nucleic acids encoding them. These sequences correspond to the variable heavy chain (VH) of mAb 8A9F9 (134 aa), the variable light chain (VL) of mAb 8A9F9 (131 aa), and three synthetic mAb constructs encoding full-length modified IgG molecules containing both the VH and VL chains (729 aa, 732 aa, and 732 aa, respectively). The VH chain of mAb 8A9F9 (SEQ ID NO.: 3) contains the following amino acid sequence: MNFGLSLIFL VLILKGVQCE VQLVESGGGL VKPGGSLKLS CAASGFTFSS YAMSWVRQSP EKRLEWVAEI SSGGSYTYYP DTVTGRFTIS RDNAKNTLYL EMSSLRSEDT AMYYCASDGY YSHWGQGTSV TVSS (134 aa). The VL chain of mAb 8A9F9 (SEQ ID NO.: 4) contains the following amino acid sequence: MKLPVRLLVL MFWIPASRSD VVMTQIPLSL PVSLGDQASI SCRSSQSLVH SNGNTYLHWY LQKPGQSPKL LIYKVSNRFS GVPDRFSGSG SGTDFTLKIS RVEAEDLGVY FCFQSTHVPP TFGGGTKLEI K (131 aa).
The broadest claims fail to set forth sufficient structural characteristics for any given anti-ZIKV E antibody. With the exception of the limited examples provided in the specification, there is no additional discussion about suitable framework regions (FRs) or VH and VL CDRs. There is no discussion about the epitope(s) recognized by any given antibody. The disclosure also fails to provide any guidance pertaining to the molecular determinants modulating antigen-antibody binding interactions. For any given antibody, which amino acids are sine qua non for antigen binding? Concerning those variant sequences, the disclosure fails to provide any guidance pertaining to those amino acid residues that should be modified. Examining just the VH chain of 8A9F9 (SEQ ID NO.: 3), 5% genetic variation would encompass upwards of 7 amino acid insertions, deletions, or substitutions anywhere in the antibody corresponding to over ~1 x 1022 variant antibody sequences.1 The antibodies encompassed by SEQ ID NO.: 13 (729 aa) would encompass upwards of 36 amino acid insertions, deletions, or substitutions anywhere in the antibody molecule. Moreover, it has been well-documented that single or multiple amino acid substitutions, insertions, or deletions can abrogate or impair antibody binding activity (Chen et al., 1992; Liu et al., 1999; Xiang et al., 1999; Winkler et al., 2000). The disclosure fails to provide a sufficient number of antibody variants that would support the claim breadth. The disclosure also fails to identify those amino acid residues that are sine qua non for antigen-antibody binding interactions.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicants were not in possession of a sufficient number of anti-ZIKV E antibodies to support the claim breadth desired.
Applicants’ traverse and submit that literal support for each and every species is not required in order to satisfy the written description requirement. The invention need not be described ipsis verbis to meet the requirements. These arguments have been carefully considered but are not deemed to be persuasive for the reasons of record clearly set forth supra.
Furthermore, an applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 U.S.P.Q.2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 U.S.P.Q.2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 U.S.P.Q.2d 1016, 1021 (Fed. Cir. 1991).
Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 U.S.P.Q. 118, 123 (C.C.P.A. 1967).
One of the primary issues with the claimed invention is that the claims encompass an inordinate number of antibody variants. However, the disclosure fails to identify the VH and VL CDRs, as well as, any relevant portions of the FR that are required for binding. The disclosure fails to teach which amino acids should be targeted for replacement and which portions of the antibody molecule can tolerate insertions and/or deletions. Accordingly, the skilled artisan cannot readily envisage any antibody variant.
Action Is Final
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 C.F.R. § 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Janet L. Andres, Ph.D., can be reached at (571) 272-0867. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 20 September, 2025
1 These calculations were performed as follows: TV=(NY)(X!)/(Y!)((X-Y-1)!), wherein, TV=the total number of variant sequences, N=the number of amino acids or nucleotides that can be substituted (i.e., if any of the 20 naturally occurring amino acids can be substituted, N=19; if any of the four naturally occurring nucleotides can be substituted, N=3), Y=the number of amino acids/nucleotides in the parent sequence that can be substituted (i.e., if the amino acid sequence is 100 aa in length and 10% genetic variation is allowed, Y=10 [100@10%]), and X=the total sequence length of the sequence of interest.