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 .
Election/Restrictions
Applicant’s election of Group I and species, nucleotides 1-29834 of SEQ ID NO:4 in the reply filed on August 08, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 14, 18, 22, 38-43, and 45-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Claims 1, 2, 4, 8, 10, 11, 13, 14, 17-20, 22, 24-26, 28, 30-32, 34-43, 45, and 46 are pending in this application and were examined on their merits. Of the above, claims 14, 18, 22, 38-43, 45, and 46 were withdrawn from consideration.
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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. 62/966,750 and 63/048,942, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The Washington isolate (Accession number MN985325.1) and the deletion of the furin cleavage site were not disclosed in the prior filed application. These were first disclosed in Application No. 63/048,942 on July 07, 2020. Accordingly claims 4 and 19 are not entitled to the benefit of the prior application.
The disclosure of the prior-filed application, Application No. 62/966,750, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
SEQ ID NO:7 was not disclosed in the prior filed applications. These were first disclosed in Application No. 63/079,337 on September 16, 2020. Accordingly claims 20 and 32 are not entitled to the benefit of the prior applications.
Specification
The use of the term TRIzol™, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 2, 4, 8, 10, 11, 13, 17, 19, 20, 30, and 31 objected to because of the following informalities: dependent claims should start with the article "the" rather than "a/an". Appropriate correction is required.
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.
Claim 4 is 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 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 inventors, at the time the application was filed, had possession of the claimed invention.
Instant claim 4, recites, inter alia, “Washington isolate of SARS-CoV-2 coronavirus having a nucleic acid sequence of GenBank accession no. MN985325.1.” MPEP 608.01(p) provides:
d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference.
Here, the sequence of the Washington isolate of SARS-CoV-2 coronavirus recited in claim 4 constitutes essential subject matter and, therefore, reference to the nucleotide sequence in an accession number constitutes an improper incorporation by reference. See also MPEP § 2422 (III).
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 and 31 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.
Claim 4 recites “having a nucleic acid sequence” which is indefinite because it is unclear if the claim encompasses nucleic acid sequences that comprise (i) the full length of the claimed sequence or (ii) any portion of the sequence including any dinucleotide or larger oligonucleotides. For the purposes of compact prosecution and applying prior art, claim 4 was interpreted as “comprising the nucleic acid sequence.”
Claim 31 recites the limitation "[a] modified SARS-CoV-2 coronavirus of claim 1" in the preamble. There is insufficient antecedent basis for this limitation in the claim.
For the purposes of compact prosecution and applying prior art, claim 31 was interpreted as “the modified SARS-CoV-2 coronavirus of claim 28.”
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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.
The factual inquiries 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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
Claims 1, 2, 8, 17, 24-26, 28, and 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over Kew, et al. (US 20170354727 A1, hereinafter "Kew") and further in view of Taylor, et al. (Labome MATER METHODS 2020;10:1867, IDS filed July 22, 2022, hereinafter "Taylor").
Regarding claim 1, Kew teaches a polynucleotide encoding one or more viral proteins or one or more fragments thereof of a parent SARS-CoV (¶0400 and FIGS. 11A-11C) wherein the polynucleotide is recoded compared to its parent SARS-CoV coronavirus polynucleotide (¶0402,), and wherein the amino acid sequence of the one or more viral proteins, or one or more fragments thereof of the parent SARS-CoV coronavirus encoded by the polynucleotide remains the same, or wherein the amino acid sequence of the one or more viral proteins or one or more fragments thereof of the parent SARS-CoV coronavirus encoded by the polynucleotide comprises up to 20 amino acid substitutions, additions, or deletions (¶0402 and Table 6).
Kew further teaches that “[p]athogens with deoptimized codons can be used to increase the phenotypic stability of attenuated vaccines” (¶0003). Kew does not teach that SARS-CoV is a SARS-CoV-2 coronavirus.
However, Taylor teaches that the spike protein of SARS-CoV-2 is a potential vaccine target (pg. 2 ¶1 and Abstract). Since Taylor teaches that spike protein of SARS-CoV-2 is a potential vaccine target, it would have been prima facie obvious to one of ordinary skill in the art to have combined the spike protein of SARS-CoV-2 taught by Taylor and subject it to the deoptimization taught by Kew to advantageously increase the phenotypic stability of the resulting vaccine.
Regarding claim 2, Kew teaches that the parent SARS-CoV coronavirus is a natural isolate SARS-CoV (¶0402). Kew does not teach that SARS-CoV is a SARS-CoV-2 coronavirus.
Regarding claim 8, Kew teaches that the polynucleotide is recoded by reducing codon usage bias compared to its parent SARS-CoV coronavirus polynucleotide (¶0402 and Example 2 ¶0292). Kew does not teach that SARS-CoV is a SARS-CoV-2 coronavirus.
Regarding claim 17, Kew teaches a recoded nucleotide sequence of a spike protein (¶0402) and, as discussed above, Taylor teaches the spike protein of SARS-CoV-2 as a potential vaccine target.
Regarding claim 24, Kew teaches that “the deoptimized coding sequence [(polynucleotide)] can be part of a vector” (¶0267).
Regarding claim 25, Kew teaches that “[a] vector can transduce, transform or infect a cell, thereby causing the cell to express nucleic acid molecules or proteins other than those native to the cell” (¶0223).
Regarding claim 26, Kew teaches that the cell being used to express non-native (SARS-CoV) proteins is a Vero cell (¶0250 and 0253).
Regarding claim 28, Kew teaches that a SARS containing the deoptimized polypeptide can be generated with standard methods (¶0402)
Regarding claim 34, Kew teaches a deoptimized SARS-CoV as a vaccine (immunogenic composition) (¶0222).
Regarding claim 35, Kew teaches a SARS-CoV immunogenic composition (vaccine) can include a pharmaceutically acceptable carrier (¶0024).
Regarding claim 36, Kew teaches a SARS-CoV immunogenic composition (¶0222).
Regarding claim 37, Kew teaches as SARS-CoV immunogenic composition that includes a pharmaceutically acceptable carrier (¶0024).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Kew and Taylor as applied to claims 1, 2, 8, 17, 24-26, 28, and 34-37 above, and further in view of Harcourt, et al. (Emerg Inect Dis. 2020 Jun;26(6):1266-1273, hereinafter “Harcourt”).
As discussed above, claim 4 was afforded an effective filing date of July 07, 2020 because the Washington isolate (Accession No. MMN985325.1) was not disclosed in prior filed applications.
Regarding Claim 4, Kew and Taylor do not teach the Washington isolate of SARS-CoV-2 having a nucleic acid sequence of GenBank accession no. MN985325.1. However, Harcourt teaches the Washington isolate of SARS-CoV-2 (Whole-Genome Sequencing, pg. 1268). 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 have modified Kew and Taylor to incorporate the Washington isolate of SARS-CoV-2 as taught by Harcourt to advantageously utilize the most recent SARS-CoV-2 isolate at the time of filing. Harcourt recognizes the use of the Washington isolate for research and attenuation with a reasonable expectation of success because the use of isolates of new viruses in research is known, successfully demonstrated, and commonly used as evidenced by the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 10-11, 13, 20, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Kew and Taylor as applied to claims 1, 2, 8, 17, 24-26, 28, and 34-37 above, and further in view of Wimmer, et al. (WO 2008121992 A2, hereinafter “Wimmer”).
Regarding claim 10, Kew and Taylor do not teach the amount of codon pair bias between the parent and recoded viral proteins. However, Wimmer teaches an attenuated virus (SARS-CoV) where the recoded protein encoding sequence has a codon pair bias of -0.05 or less, -0.1 or less, -0.3 or less, or -0.4 or less (Claims 1, 5-8, and 24). 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 have modified Kew to incorporate the amount of codon pair bias as taught by Wimmer to advantageously deoptimize and attenuate coronaviruses. Both Kew and Wimmer recognize deoptimization through either codon pair bias or codon usage bias with a reasonable expectation of success because the deoptimization of viruses through codon pair bias is known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 11, Kew and Taylor do not teach that the polynucleotide is CPB deoptimized compared to the parent polynucleotide. However, Wimmer teaches an attenuated virus (SARS-CoV) where the polynucleotide is CPB deoptimized (¶0124). 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 have modified Kew to incorporate the codon pair bias is compared to the parent polynucleotide as taught by Wimmer to advantageously deoptimize and attenuate coronaviruses. Both Kew and Wimmer recognize deoptimization through either codon pair bias or codon usage bias with a reasonable expectation of success because the deoptimization of viruses through codon pair bias is known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 13, Kew and Taylor do not teach that the CPB deoptimization is based on CPB in humans. However, Wimmer teaches the relative codon deoptimization index which compares quantifies the cumulative effect of a particular codon bias against the general codon distribution of the human genome (¶0206). 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 have modified Kew to incorporate the codon pair bias compared to humans as taught by Wimmer to advantageously deoptimize and attenuate coronaviruses. Both Kew and Wimmer recognize deoptimization through either codon pair bias or codon usage bias with a reasonable expectation of success because the deoptimization of viruses through codon pair bias is known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 20, Kew and Taylor do not teach polynucleotides having the sequence of SEQ ID NO:4 or SEQ ID NO:7. However, Wimmer teaches a computer-based algorithm that readily manipulates the codon pair bias of any coding region (¶0136-0144). This algorithm can also be used to deoptimize the codon base pairs chosen (¶0145). 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 have combined the teachings of Kew, Taylor, and Wimmer to formulate a polynucleotide having the sequences of SEQ ID NO:4 or SEQ ID NO:7, given that Kew teaches deoptimization of coronaviruses, Wimmer teaches a computer-based algorithm to determine codon pair bias for use in deoptimization, and Taylor teaches the use of the SARS-CoV-2 as a coronavirus. The algorithm taught by Wimmer suggests that deoptimized polynucleotide sequences can be found by inputting the desired polynucleotide sequence into the computer and the algorithm analyses all the codons for deoptimization. The algorithm can also account for desired reduction or increase in codon-pair scores allowing for optimal deoptimization. As such, as absent, evidence to the contrary, the claimed sequences were readily derivable using the algorithm taught by Wimmer.
One of ordinary skill in the art would have been motivated to combine the teachings of Kew, Wimmer, and Taylor for the benefit of formulating a composition for viral attenuation/deoptimization with controllable codon pair bias. One of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Kew, Taylor, and Wimmer given that the computer-based algorithm is well known, successfully, demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claims 30 and 31, Wimmer further teaches that deoptimizing codons in a viral (SARS-CoV) genome decreases protein translation, decreasing expression, and allowing for viral attenuation (¶0008). As such, as absent, evidence to the contrary, reduced protein expression is encompassed by and flow from practice of Kew, Taylor, and Wimmer.
Regarding claim 32, Kew and Taylor do not teach polynucleotides having the sequence of SEQ ID NO:4 or SEQ ID NO:7. However, Wimmer teaches a computer-based algorithm that readily manipulates the codon pair bias of any coding region (¶0136-0144). This algorithm can also be used to deoptimize the codon base pairs chosen (¶0145). 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 have combined the teachings of Kew, Taylor, and Wimmer to formulate a polynucleotide have the sequences of SEQ ID NO:4 or SEQ ID NO:7, given that Kew teaches the deoptimization of coronaviruses and modified coronaviruses as described above, Wimmer teaches a computer-based algorithm to determine codon pair bias for use in deoptimization, and Taylor teaches the use of the SARS-CoV-2 as a coronavirus. The algorithm taught by Wimmer suggests that deoptimized polynucleotide sequences can be found by inputting the desired polynucleotide sequence into the computer and the algorithm analyses all the codons for deoptimization. The algorithm can also account for desired reduction or increase in codon-pair scores allowing for optimal deoptimization. As such, as absent, evidence to the contrary, the claimed sequences were readily derivable using the algorithm taught by Wimmer.
One of ordinary skill in the art would have been motivated to combine the teachings of Kew, Wimmer, and Taylor for the benefit of formulating a composition for viral attenuation/deoptimization with controllable codon pair bias and use that polynucleotide to create a modified SARS-CoV-2. One of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Kew, Taylor, and Wimmer given that the computer-based algorithm is well known, successfully, demonstrated, and commonly used as evidenced by the applied prior art.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kew and Taylor as applied to claims 1, 11, and 25 above, and further in view of Chappell, et al. (WO 2018176103 A1, hereinafter “Chappell”).
As discussed above, claims xxx were rendered prima facie obvious by the teaching of Kew and Taylor.
Regarding claim 19, Kew and Taylor do not teach elimination of the furin cleavage site. However, Chappell teaches deletion of the furin cleavage site in coronaviruses (Claims 17 and 22). 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 have modified Kew and Taylor to incorporate elimination of the furin cleavage site as taught by Chappell to advantageously deoptimize and attenuate coronaviruses by eliminating an essential component. Chappell recognizes the elimination of the furin cleavage site in coronaviruses with a reasonable expectation of success because the deoptimization of viruses through codon pair bias is known, successfully demonstrated, and commonly used as evidenced by the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672