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
The amendment filed 22 April 2026 in which claims 1, 8, 10-11, 13, 20, 24-26, 28, 31-32, and 34-43 were amended, claims 49-51 were added, claims 38-43 and 45-46 remained withdrawn, and claims 2, 4, 14, 17-19, 22, and 30 were cancelled has been entered.
Claims 1, 8, 10-11, 12, 20, 24-26, 28, 31-32, 34-37, and 49-51 are under examination on the merits.
Claim Objections
(Previous objection, withdrawn). Applicant’s amendments to claims 2, 4, 8, 10, 11, 13, 17, 19-20, and 30-31 submitted on 22 April 2026 have overcome the objection previously set forth in the Non-Final Office Action mailed 15 December 2025.
(New objection). Claims 34, 36, and 50-51 are objected to because of the following informalities: “a modified SARS-CoV-2” should read “the modified SARS-CoV-2 in claim 34 line 3, claim 36 line 3, claim 50 line 3, and claim 51 line 2. 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.
(Previous rejection, withdrawn as to claim 4 due to cancellation of the claim). Claim 4 was 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 Applicant cancelled claim 4 on the response filed 22 April 2026.
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.
(Previous rejection, withdrawn as to claim 4 due to cancellation of the claims). Claim 4 was 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. The Applicant cancelled claim 4 on the response filed 22 April 2026.
(Previous rejection, withdrawn as to claim 31). Claim 31 was 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. This rejection is withdrawn due to Applicant’s amendment to claim 31 submitted 22 April 2026.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous rejection, withdrawn as to claims 1, 2, 8, 17, 24-26, 28, and 34-37, claim 2, 17 rejection withdrawn due to cancellation of the claim). Claims 1,2, 8, 17, 24-26, 28, and 34-37 were rejected under 35 U.S.C. 103 as being unpatentable over Kew and further in view of Taylor.
(Previous rejection, withdrawn as to claim 4 due to cancellation of the claim). Claim 4 was 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 and further in view of Harcourt.
(Previous rejection, withdrawn as to claims 10-11, 13, 20, and 30-32, claim 30 rejection withdrawn due to cancellation of the claim). Claims 10-11, 13, 20, and 30-32 were 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 and further in view of Wimmer.
(Previous rejection, withdrawn as to claims 19 due to cancellation of the claim). Claim 19 was 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 and further in view of Chappell.
(New rejection). Claims 1, 8, 10-11, 13, 20, 24-26, 28, 31-32, 34-37, and 49-51 were rejected under 35 U.S.C. 103 as being unpatentable over Kew and further in view of Johnson (Wuhan 2019 Novel Coronavirus - 2019-nCoV published by Labome https://www.labome.com/method/Wuhan-2019-Novel-Coronavirus-2019-nCoV.html with Wayback machine with publication date of Jan 27 2020 having the link https://web.archive.org/web/20200127173902/https://www.labome.com/method/Wuhan-2019-Novel-Coronavirus-2019-nCoV.html), and Wimmer.
Regarding claim 1, Kew teaches a polynucleotide encoding a SARS-CoV coronavirus wherein the polynucleotide encodes a SARS-CoV spike protein (¶0402). 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, Johnson teaches that SARS-CoV-2 also contains a spike protein (Table 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the SARS-CoV spike protein taught by Kew for the SARS-CoV-2 spike protein taught by Johnson. Kew teaches that deoptimization can be used with any coronavirus (¶0400). One of skill in the art would have had a reasonable expectation of success for substituting the SARS-CoV taught by Kew for the SARS-CoV-2 taught by Johnson because they both teach coronaviruses.
Kew and Johnson 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, Johnson, 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 Johnson teaches that SARS-CoV-2 is 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, Johnson, and Wimmer 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, Johnson, and Wimmer given that the computer-based algorithm is well known, successfully, demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 8, Kew teaches that the polynucleotide encoding the SARS spike glycoprotein is recoded by reducing codon usage bias compared to its parent SARS-CoV coronavirus polynucleotide (¶0402 and Example 2 ¶0292), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 10, Kew and Johnson 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 Johnson 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 Johnson 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 claims 20 and 49, Kew and Johnson 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, Johnson, 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 Johnson teaches that SARS-CoV-2 is a coronavirus (Table 2). 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, Johnson, and Wimmer 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, Johnson, and Wimmer given that the computer-based algorithm is well known, successfully, demonstrated, and commonly used as evidenced by the applied prior art.
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), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 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, Johnson, and Wimmer.
Regarding claim 32, Kew and Johnson 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, Johnson, 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 Johnson teaches that SARS-CoV-2 is 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, Johnson, and Wimmer given that the computer-based algorithm is well known, successfully, demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 34, Kew teaches a deoptimized SARS-CoV as a vaccine (immunogenic composition) (¶0222), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 35, Kew teaches a SARS-CoV immunogenic composition (vaccine) can include a pharmaceutically acceptable carrier (¶0024), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 36, Kew teaches a SARS-CoV immunogenic composition (¶0222), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 37, Kew teaches as SARS-CoV immunogenic composition that includes a pharmaceutically acceptable carrier (¶0024), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus with a spike glycoprotein (Table 2).
Regarding claim 50, Kew teaches that the attenuated/deoptimized coronavirus immune composition elicits a protective immune response when administered to a subject (¶0181), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus (Table 2).
Regarding claim 51, Kew teaches that the attenuated/deoptimized coronavirus immune composition elicits an immune response when administered to a subject (¶0024-0025), as discussed above Johnson teaches that SARS-CoV-2 is also a coronavirus (Table 2).
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.
Response to Arguments
Applicant contends on page 8 of the Remarks submitted on 22 April 2026 that the version of Taylor, et al. available on the IDS and used in the rejection had a publication date after the effective filing date of the application
In response: Applicant’s arguments with respect to the rejections of claims 1, 8, 10-11, 13, 20, 24-26, 28, 31-32, and 34-37 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kew, Johnson, and Wimmer.
Applicant contends on pages 8-9 of the Remarks submitted on 22 April 2026 that Wimmer does not teach the level of deoptimization of which gene will work as a vaccine or immune composition. That determining the deoptimized SARS-CoV-2 sequence that can be used as a vaccine requires experimentation such that the results are not reasonably predictable.
In response: Wimmer teaches a platform that will deoptimize sequence to attenuate viruses for use in vaccines. Given the SARS-CoV-2 spike protein, the platform would generate deoptimized SARS-CoV-2 spike protein sequences including instant SEQ ID NOs: 4 and 7. Routine optimization of the readily available sequences, using standard computer-based algorithms readily available before the effective filing date of the claimed invention, would then lead to SEQ ID NOs: 4 and 7 being usable as vaccines/immunogenic compositions against SARS-CoV-2. See MPEP 2144.05. Moreover, nothing in the record reasonably suggests any unexpected results for the instant sequence. The prior art provides a clear teaching, suggestion, and motivation to utilize codon deoptimization to obtain the known advantage of increased the phenotypic stability of attenuated vaccines and reduce the pathogens replicative fitness with a reasonable expectation of success. Furthermore, all codons for each amino acid are known and deoptimizing the codon will invariably lead to the same protein as the amino acid stays the same.
Conclusion
NO CLAIMS ARE ALLOWED
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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