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 30 September, 2025. Claims 1-67 have been canceled without prejudice or disclaimer and new claims 68-88 introduced. Applicant’s election of Group I and the species of SEQ ID NO.: 15 is noted. Because Applicant did not distinctly and specifically point out the purported errors in the restriction requirement, the election has been treated as an election without traverse (M.P.E.P. § 818.03(a)). Accordingly, claims 83, 84, 87, and 88 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention. Claims 68-82, 85, and 86 are currently under examination.
37 C.F.R. § 1.98
The information disclosure statement filed 22 June, 2023, has been placed in the application file and the information referred to therein has been considered. Applicant is reminded that the listing of references in the specification (e.g., see pp. 173-177, 190-193, and 211-213) is not a proper information disclosure statement. 37 C.F.R. § 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and M.P.E.P. § 609.04(a), subsection I. 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.
37 C.F.R. § 1.57(d)
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see pp. 38, 58, 63, 75, 76, and 91). Applicant should peruse the entire specification and delete all embedded hyperlinks and/or other forms of browser-executable code. See M.P.E.P. § 608.01.
37 C.F.R. § 1.821-1.825
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 C.F.R. § 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 C.F.R. § 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 C.F.R. § 1.831-1.835. This "Sequence Listing XML" part of the disclosure may be submitted:
1. In accordance with 37 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 via the USPTO’s patent electronic filing system (Patent Center) (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application-process/filing-online/legal-framework-efs-web), 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 C.F.R. § 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 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 C.F.R. § 1.52(e)(1)(ii), labeled according to 37 C.F.R. § 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 C.F.R. § 1.52(e)(8) and 37 C.F.R. § 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.
This application contains sequence disclosures (e.g., see GGGGS on pp. 5, 7, 9, etc., RRAR on pp. 33, 61, 68, 180, etc., and RRAR in Fig. 8A) 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 for the reason(s) set forth below. Applicants are reminded that the sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. See 37 C.F.R. § 1.821(a) and M.P.E.P. § 2421.02.
With respect to sequences appearing in the specification which are not identified by sequence identifiers in accordance with 37 C.F.R. § 1.821(d), Applicant must provide the following:
- A substitute specification in compliance with 37 C.F.R. § 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.
With respect to sequences appearing in the drawings which are not identified by sequence identifiers in accordance with 37 C.F.R. § 1.821(d), Applicant must provide the following:
- Replacement and annotated drawings in accordance with 37 C.F.R. § 1.121(d) inserting the required sequence identifiers; AND/OR
- A substitute specification in compliance with 37 C.F.R. § 1.121(b)(3) and 1.125 inserting the required sequence identifiers 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.
The specification is objected to for failing to comply with the sequence requirements.
37 C.F.R. § 1.84
The drawings (e.g., see Fig. 8A) are objected to because they fail to comply with the sequence requirements set forth supra. Upon the submission of a corrected sequence listing, Applicant may amend the brief description of the drawings to incorporate the requisite sequence identifiers. Alternatively, corrected drawing sheets in compliance with 37 C.F.R. § 1.121(d) will be required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 C.F.R. § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claim 86 is rejected 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. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
Claim 86 is directed toward a cell line or chicken embryonated egg comprising the propagating the recombinant NDV of claim 68. This recitation is vague and indefinite because the precise genotypic/phenotypic characteristics of the cell line or chicken egg are not readily manifest. For example, does the cell line or egg comprise a stable transfectant comprising an expression vector that encodes a replication-competent NDV genome? Alternatively, does the cell line or egg comprise multiple cotransfectants comprising expression vectors encoding a replication-impaired NDV genome, L, NP, and P proteins? Appropriate correction is required.
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 68, 70-77, 79-82, 85, and 86 are 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).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
The claims are directed toward a modified recombinant Newcastle disease virus (NDV) genome, or virion comprising said genome, comprising a transgene encoding a chimeric protein that is “at least 90% identical” to one of SEQ ID NOS.: 13, 15, 17, and 19 (claims 68 and 77). The chimeric protein of SEQ ID NO.: 15 comprises 1,268 amino acids and contains the SARS-CoV-2 S protein and portions of the NDV F transmembrane (TM) and cytoplasmic (CYT) domains. The claims encompass an inordinate number of variant S-F proteins. Considering the broadest range (10% amino acid sequence variation) would encompass upwards of ~2 x 10343 variant S-F protein sequences.1 This calculation assumes that upwards of 127 amino acids can be replaced at any location in the S-F fusion. In addition to the replacement of individual amino acids, the claims also encompass insertions and deletions at any location in the fusion protein which introduces additional variation. Perusal of the disclosure failed to identify a reasonable number of SARS-CoV-2 S-NDV F variants. There was no discussion about the identification of suitable molecular determinants that should be targeted for modification. Finally, it has been well-documented that even single amino acid substitutions can abrogate S protein function (Lin et al., 2008; Corver et al., 2009). Lin et al. (2008) performed mutagenesis studies on the SARS-CoV S protein and demonstrated that even single amino acid substitutions could abrogate protein function. Corver et al. (2009) performed mutagenesis studies on the aromatic domain of the S protein and noted that single amino acid replacements abrogated viral entry.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicant’s were not in possession of a sufficient number of S-F variants to support the current claim breadth.
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.
For the purpose of applying prior art, the S-F fusion protein of SEQ ID NO.: 15 is supported by U.S. Prov. Appl. No. 63/057,267, filed 27 July, 2020. However, the earlier relied upon provisional applications do not support the claimed chimera.
Claims 68, 68, 71-73, 75-78, 80-82, and 86 are rejected under 35 U.S.C. § 103 as being unpatentable over DiNapoli et al. (June 2007, Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens, PNAS 104(23):9788-9793), in view of Wu et al. (March 2020, A new coronavirus associated with human respiratory disease in China, Nature 579:265-284, published online 03 February, 2020), Wu et al. (February 2020, Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome, GenBank MN908947.3, pp. 1-12), Park et al. (May 2006, Engineered viral vaccine constructs with dual specificity: Avian influenza and Newcastle disease, PNAS 103(21):8203-8208), and Hsieh et al. (September, 2020, Structure-based design of prefusion-stabilized SARS-CoV-2 spikes, Science 369:1501-1505, published online 23 July, 2020). Claim 68 is directed toward a recombinant Newcastle disease virus (NDV) comprising a packaged genome comprising: a transgene comprises a nucleotide sequence encoding a chimeric protein, wherein the chimeric protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO.: 13, 15, 17, or 19. Claim 69 references the S protein of SEQ ID NO.: 15. Claims 70 and 71 are directed to various chimeric protein modifications (862RRAR865 to A (claim 70) and the inclusion of the NDV F TM/CT regions (claim 71)). Claims 72 and 73 further define the nature of the NDV recombinant (e.g., the virion contains the recombinant protein (claim 72); the NDV genome contains the F, MP, M, L, P, and HN genes (claim 73). Claims 75 and 76 specify the location of the transgene (e.g., between two NDV transcription units) and NDV isolate (e.g., LaSota strain). Claims 77 and 78 reference a recombinant NDV virion containing a chimeric protein comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 13, 15, 17, or 19 (claim 77), or comprises the sequence identifier of interest (claim 78). Claim 80 simply includes the utilization of a linker to join the S and F domains. Claims 81 and 82 are directed toward immunogenic compositions comprising the recombinant NDV. Finally, claim 86 references a cell line or embryonated egg comprising the recombinant.
The chimeric protein of SEQ ID NO.: 15 is directed toward a SARS-CoV-2 S/NDV F fusion protein. This protein comprises the ectodomain of the SARS-CoV-2 surface protein (GenBank Accession No. MN908947) and the TM/CT domains of the NDV F protein to improve virion incorporation. This protein also contains the HexaPro mutations (F817P, A892P, A899P, A942P, K986P, and V987P).
DiNapoli et al. (2007) disclose the preparation of recombinant NDV vaccine vectors expressing the SARS-CoV-1 S and RBD domain (see Fig. 1, next page; Results, Design of the Vaccine Constructs, p. 9789; and Materials and Methods, Viruses and Immunization and Challenge of AGM, pp. 9792-9793). The S gene was inserted between the P and M genes. NDV recombinants were recovered and passaged on HEp-2 cells and embryonated chicken DF-1 cells. Two different vaccine vectors were employed, one comprising the mesogenic NDV-BC strain and one employing the lentogenic LaSota NDV-VF strain. The authors reported that inoculation of the upper respiratory tract with NDV recombinants expressing the SARS-CoV-1 S protein was highly immunogenic and produced protective immune responses against high challenge doses of SARS-CoV-1 (see Discussion, p. 9791). The authors conclude that NDV vectors offer several advantages over alternative vaccine strategies (see Discussion, p. 9792). This teaching does not disclose the modified SARS-CoV-2 S-NDV F chimeric protein of SEQ ID NO.: 15.
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Wu et al. (March 2020) and Wu et al. (February 2020) disclose the isolation, cloning, and characterization of a novel SARS-CoV-2 (2019-nCoV), isolate Wuhan. This isolate was responsible for a world-wide severe acute respiratory syndrome (SARS) outbreak. The former publication discloses the isolation and characterization of the Wuhan isolate. The amino acid sequence of the S protein was determined and submitted to GenBank (Wu et al., February 2020; GenBank Accession No. MN908947). This teaching does not disclose an SEcto/FTM/CT fusion protein.
Park et al. (2006) discloses the preparation of a bivalent NDV vaccine vector encoding a chimeric viral surface protein. In particular, a chimeric protein comprising the influenza H7 virus hemagglutinin (HA) surface protein (ectodomain) and the NDV F transmembrane (TM) and cytoplasmic (CT) domains was generated (see Fig. 3A, next page). The gene encoding the chimeric protein was inserted between the P and M genes of the rNDV vector. The authors demonstrated that including the NDV F protein TM/CT region significantly improved the incorporation of the chimeric protein into rNDV virions (see Results, Improved Incorporation of AIV H7 HA Protein into rNDV Virions, pp. 8205-8206). This teaching does not disclose the modified SARS-CoV-2 S-NDV F chimeric protein of SEQ ID NO.: 15.
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Hsieh et al. (2020) discloses the preparation of a SARS-CoV-2 spike protein (HexaPro) with six mutations (F817P, A892P, A899P, A942P, K986P, and V987P) that produce a stabilized prefusion protein (see p. 1504). The inclusion of these mutations produced a protein with higher protein yields and greater stability as compared to the wildtype spike. In addition to higher expression levels, HexaPro mutants were more heat-resistant, more stable at room temperature, and suffered less degradation during freeze-thaw cycles. This teaching does not disclose the modified SARS-CoV-2 S-NDV F chimeric protein of SEQ ID NO.: 15.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the NDV vaccine expression vector of DiNapoli et al. (2007), to express a modified SARS-CoV-2 spike (S) protein. In particular, one of ordinary skill in the art would have been motivated to modify the Wu S protein (GenBank Accession No. MN908947) of Wu et al. (March 2020) and Wu et al. (February 2020), to incorporate the F CT/TM domains of Park et al. (2006), since Park and colleagues demonstrate that S/FCT/TM mutants have a higher rate of incorporation into NDV recombinant viral particles. One of ordinary skill in the art would have also been motivated to further include the HexaPro modifications taught by Hsieh et al. (2020), since Hsieh and associates demonstrate that S proteins carrying these mutations display higher expression levels and are more stable.
Claims 70 and 79 are rejected under 35 U.S.C. § 103 as being unpatentable over DiNapoli et al. (2007), in view of Wu et al. (March 2020), Wu et al. (February 2020), Park et al. (2006), and Hsieh et al. (2020), as applied supra to claim 68, and further in view of Amanat et al. (2020). The claims further require the inclusion of a mutation to the polybasic cleavage site (682RRAR685 to A). Amanat et al. (2020) disclose the preparation of stable SARS-CoV-2 S proteins comprising mutation of the polybasic cleavage site (682RRAR685 to A). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the S protein by deleting the polybasic cleavage site to produce a more stable immunogen.
Claim 74 is rejected under 35 U.S.C. § 103 as being unpatentable over DiNapoli et al. (2007), in view of Wu et al. (March 2020), Wu et al. (February 2020), Park et al. (2006), and Hsieh et al. (2020), as applied supra to claim 68, and further in view of Li et al. (2005). The claim further requires the inclusion of a L289A mutation in the NDV F protein. Li et al. (2005) demonstrate that L289A F mutants promote NDV fusion more efficiently than wildtype. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the S protein by incorporating the L289A F mutation. One of ordinary skill in the art would have been motivated to incorporate this mutation into the F protein to generate recombinant NDV viruses with enhanced properties.
Claim 85 is rejected under 35 U.S.C. § 103 as being unpatentable over [2], as applied supra to claim 68, and further in view of Belov et al. (2019, US 2019/0382450). Claim 85 simply references a kit comprising the claimed recombinant NDV. Belov et al. (2019) reference kits comprising a modified recombinant NDV expressing poliovirus immunogens. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the claimed recombinant NDV into a kit to facilitate its transportation and storage.
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, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
Information regarding the status of an application may be obtained from the Patent Center. Status information for published applications may be obtained from the Patent Center. Status information for unpublished applications is available through the Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 17 December, 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.