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 .
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.
Claims 4, 6, 14, 17, 20, and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 4, 6, 17, 20, and 23, the acronym “e.g.,” in parentheses, meaning “for example” and the remainder of the verbiage in parentheses, render the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention or not. See MPEP § 2173.05(d).
Instant claim 14 states that the dose of the immunogenic composition is between 103 to 106, which corresponds to plaque forming units (pfu) in paragraph [0177] of the instant published disclosure (USPgPub 2023/0248815). However, the material administered in claim 14, ultimately from claim 4 dependency, is a chimeric protein, not a virus. Therefore, the dosing units recited do not correspond to the material administered. In the interest of compact prosecution, the dosage quantities recited in the claim will be considered for a virus delivery. However, an appropriate amendment is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5, 8-16, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Rappuoli et al. (USPgPub 2006/0257852), Godeke et al. (Journal of Virology. 2000; 74 (3): 1566-1571), Oomens et al. (Journal of Virology. 2006; 80 (21): 10465-10477), and Wang et al. (Frontiers in Microbiology. 28 February 2020; 11: 298).
Rappuoli et al. teach a chimeric polypeptide comprising an ectodomain of the SARS spike protein, as recited in instant claims 1 and 2, and a transmembrane and endodomain of a heterologous virus, see paragraphs [0814 and 1558]. Paragraphs [0010, 0540, 0541, 0687, and 0688] teach RSV antigens and fragments thereof, are incorporated within the composition as a second amino acid sequence in the fusion protein. Paragraphs [0254, 0559, and 0605-0610] discuss attenuated SARS vaccine expressing chimeric proteins with heterologous sequences, as required by instant claim 5 and the nucleic acid encoding the chimeric protein of instant claim 16. The live chimeric SARS virus of Rappuoli et al. does not comprise a gene encoding RSV G, as required by instant claim 8. Paragraph [0011] teaches the inclusion of an aluminum salt adjuvant, as required by instant claims 9 and 10. Paragraphs [0865 and 0866] teach that the adjuvant is an oil-in-water emulsion comprising squalene, as required instant claim 11. Paragraphs [0552, 0861, and 1172] teach that the immunogenic composition administered results in a humoral and/or cellular immune response and is administered intranasally, as required by instant claims 12 and 13. Paragraph [0607] states that the attenuated SARS vaccine is administered at a dose ranging between 103-106 (as interpreted by the intended meaning discussed above), recited in instant claim 14. Paragraphs [0959, 1524, 1569, and 1588] teach generation of serum neutralizing antibodies, as required by instant claim 15. Paragraphs [0807 and 0823] teach that the SARS virus antigens are cloned into plasmid expression vectors, as required by instant claims 18 and 19.
Rappuoli e al. do not mention that the chimeric protein comprises the transmembrane portion of the SARS spike protein of instant claim 2 or that the c-terminal part of the fusion protein is a cytoplasmic tail portion of an RSV F protein, as required by instant clams 1 and 3.
Godeke et al. teach that the transmembrane (TM) domain of the spike protein is a requisite component for coronavirus particle formation, see the abstract and Figures 1 and 5.
Oomens et al. teach the cytoplasmic tail (CT) of the RSV F is critical for cellular localization and enhancing heterologous virus progeny (combined with VSV G protein), see the abstract and Figures 1B, 3, and 7.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included the coronavirus spike TM domain, as taught by Godeke et al., connected to the spike ectodomain of Rappuoli et al., to form coronavirus particles. It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included the CT of RSV F as taught by Oomens et al., at the c-terminus of the transmembrane-ectodomain of Godeke et al. and Rappuoli et al. to optimize cellular localization and increase virus progeny expressing heterologous RSV F ectodomain proteins.
One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success for including the spike TM domain of Godeke et al. connected to the spike ectodomain of Rappuoli et al. because Rappuoli et al. include an embodiment with a spike TM in paragraphs [0250 and 0255]. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success for including the CT of RSV F as taught by Oomens et al., at the c-terminus of the transmembrane-ectodomain of Godeke et al. and Rappuoli et al. because Rappuoli et al. teach antigenic portions of RSV F as a second antigen fused to the ectodomain of the spike protein in paragraphs [0010, 0540, 0541, 0687, and 0688] and paragraph [0801] of Rappuoli et al. teach viral neutralization and protective immunity in mice is induced when the spike antigen is truncated at the c-terminus, as instantly required. In addition, paragraph [0606] of Rappuoli et al. specifically teach preparation and generation of RSV vaccines are applicable to the SARS virus.
None of Rappuoli et al., Godeke et al., or Oomens et al. suggest that the SARS spike protein is derived from SARS-CoV-2, as instantly required.
Wang et al. do, see “2019-nCoV” depicted in Figure 2.
However, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have applied the architecture of Rappuoli et al., Godeke et al., and Oomens et al. to a SARS-CoV-2 spike protein with a reasonable expectation of success because Wang et al. teach extensive similarities between SARS and SARS-CoV-2, see the second full paragraph under “Potential Targets for Development of SARS-CoV and MERS-CoV Subunit Vaccines” and spike ectodomain fused to heterologous sequences inducing specific and neutralizing antibodies in “SARS-CoV Subunit Vaccines Based on Full-Length S Protein”.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. as applied to claims 1-3, 5, 8-16, 18, and 19 above, and further in view of instant SEQ ID NO: 1 alignment with Geneseq db access no: BJV65191 in WO2021168318 by Parks et al. (priority 21 Feb 2020).
See the teachings of Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. above. None of the references teach a sequence that has at least 85% identity to instant SEQ ID NO: 1, as required.
Geneseq db access no: BJV65191 shares 98.4% identity to instant SEQ ID NO: 1, see the description of the sequence alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have incorporated requisite sequence structures of the SARS-CoV-2 spike protein to generate an immune response against SARS-CoV-2 and prevent SARS-CoV-2 infection, see the alignment description. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have incorporated requisite sequence structures of the SARS-CoV-2 spike protein to generate an immune response against SARS-CoV-2 and prevent SARS-CoV-2 infection because Rappuoli et al. teach that the immunogenic composition comprising a SARS spike ectodomain results in a humoral and/or cellular immune response in paragraphs [0552, 0814, 0861, 1172, and 1558] and paragraphs [0959, 1524, 1569, and 1588] teach generation of serum neutralizing antibodies against the spike protein and Wang et al. teach extensive similarities between SARS and SARS-CoV-2, see the second full paragraph under “Potential Targets for Development of SARS-CoV and MERS-CoV Subunit Vaccines”.
Claims 6 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. as applied to claims 1-3, 5, 8-16, 18, and 19 above, and further in view of SEQ ID NO: 7 alignment with GenEmbl db access no MT263141 submitted 28-Mar-2020.
See the teachings of Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. above. None of the references teach a sequence that has at least 85% identity to instant SEQ ID NO: 7, as required.
GenEmbl db access no: MT263141 shares 98.1% identity to instant SEQ ID NO: 7, see the description of the sequence alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have incorporated requisite sequence structures encoding the SARS-CoV-2 spike protein to generate an immune response against SARS-CoV-2 and prevent SARS-CoV-2 infection. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have incorporated requisite sequence structures encoding the SARS-CoV-2 spike protein to generate an immune response against SARS-CoV-2 and prevent SARS-CoV-2 infection because paragraphs [0254, 0559, and 0605-0610] of Rappuoli et al. discuss attenuated SARS vaccine and paragraphs [0959, 1524, 1569, and 1588] teach generation of serum neutralizing antibodies upon administration and Wang et al. teach extensive similarities between SARS and SARS-CoV-2, see the second full paragraph under “Potential Targets for Development of SARS-CoV and MERS-CoV Subunit Vaccines”.
Claims 7, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. as applied to claims 1-3, 5, 8-16, 18, and 19 above, and further in view of Meng et al. (MBio. 2014 Oct 31; 5 (5): 10-128).
See the teachings of Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. above. None of the references teach or suggest the immunogenic vaccine composition further comprising RSV NS1 and/or NS2 proteins.
Meng et al. do, see Figure 2.
One of ordinary skill in the art prior to the instant effective filing date would have been inspired to have included the RSV NS1 and/or NS2 proteins in the immunogenic vaccine composition of Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. because Meng et al. show RSV expressing codon-deoptimized NS1/NS2 induced higher levels of neutralizing antibodies and equivalent protection against challenge in Figure 5. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have included the RSV NS1 and/or NS2 proteins in the immunogenic vaccine composition of Rappuoli et al., Godeke et al., Oomens et al., and Wang et al. because Rappuoli et al. teach one or more additional RSV antigens are included in the vaccine formulation in paragraphs [0010 and 0850].
Allowable Subject Matter
The first 1000 residues of SEQ ID NOs: 13-18, 65, 71, 77, 83, 89, 95, 101, 104-109, 113, recited in claim 23 and the first 1000 residues of 54, recited in claim 20, are found free of the prior art. A search for all of the sequences listed in their entirety is prohibited by the sequence search constraints of the Scientific and Technical Information Center of the USPTO. An updated search will be conducted upon receipt of a reply, with ameliorative claim amendments, from applicant.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/Primary Examiner, Art Unit 1671