DETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Examiner’s Note
2. The elected Group I invention claims has allowable subject matter as indicated in the office action below.
Election/Restrictions
3. Applicant’s election without traverse of Group I claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 in the reply filed on 06/11/2026 is acknowledged.
The Applicant elected a species, the nucleic acid sequence of SEQ ID NO: 17187. Applicant indicated that Group I claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 read on the elected species.
For compact prosecution, the search for non-elected species was extended to SEQ ID NO: 15310 (recited in claim 1) and SEQ ID NOs: 19064 and 20941 (recited in claim 12). The non-elected species are interpreted to read upon the elected Group I claims 1, 12, 44-45, 47-49, 54-56, 97-99, 107-108, 111, 116, and 147.
Status of Claims
4. Claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, 147, 150, and 157 are pending.
5. Claims 150 and 157 are withdrawn being in the non-elected Groups II and III inventions.
6. Claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 are under examination.
Claim Objections
7. Claim 12 is objected to because of the following informalities:
The claim 12 line 2 has grammatical error “consist at” that need to be corrected to “consist of”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. 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.
Claim 12 is 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 12 comprises both broad (comprises) and narrow (consist at) limitations in the same claim.
It is similar to a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation comprises , and the claim also recites consist which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Interpretation
9. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1: The instant claim 1 is directed to a pharmaceutical composition comprising at least one nucleic acid comprising at least one RNA coding sequence encoding at least one antigenic peptide or protein from at least one Coronavirus, wherein the at least one antigenic peptide or protein is a nucleocapsid protein (N) having a sequence at least 90% identical to the sequence according to SEQ ID No.: 15310.
Claim 1 is interpreted to comprise a mRNA encoding a nucleocapsid protein (N) having a sequence at least 90-100% identical (accommodating 10% sequence variation) to the sequence according to SEQ ID No.: 15310. Under BRI the 90% identity (accommodating 10% sequence variation) comprise many variant species of mRNA encoding a coronavirus nucleocapsid protein (N).
The dependent claims 12 comprise an added limitation that a nucleocapsid protein (N) being identical or at least 85% identical to any one of the nucleic acid sequences selected from SEQ ID NOs: 17187, 19064 and 20941.
The dependent claims 45 and 47-48 comprise limitations on coronavirus structural (e.g. M) proteins and non-structural proteins (e.g. NSP3).
The inventions are directed to a multivalent mRNA vaccine encoding coronavirus structural and non-structural proteins.
Claim Rejections - 35 USC § 102
10. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 44-45, 49, 54, 99, 107-108, 116 and 147 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Csiszovszki et al 2021 (US10973909B1, 04/13/2021, with an earlier priority of 04/07/2020 to 16/ 842,669).
Claim 1: Csiszovszki et al 2021 is directed to a coronavirus vaccine, SARS-CoV-2 vaccine comprising protein or RNA nucleic acid vaccine pharmaceutical composition comprising SEQ ID NO: 123 (See, Col 29 for Nucleocapsid protein SEQ ID NO: 123) has 100% identity with instant SEQ ID NO.: 15310. The polypeptides and vaccines comprise T cell and/or B cell epitopes that are immunogenic in a high percentage of individuals in the human population (see, abstract, Example 1 PolyPEPI-SCoV-2 Vaccine Design corresponds to multivalent vaccine. The structural proteins include the spike (S) protein, the envelope (E) protein, the membrane (M) protein, and the nucleocapsid (N) protein, Example 4 and also see 1-4, abstract). In some embodiments, the compositions disclosed herein are prepared as an RNA vaccine. In some embodiments, the RNA is non-replicating mRNA or virally derived, self-amplifying RNA (See, col 14 last para, col 15).
Csiszovszki et al 2021 disclosed SEQ ID NO: 123 (See, Col 29 for Nucleocapsid protein SEQ ID NO: 123) that has 100% identity with instant SEQ ID NO.: 15310.
Query Match 100.0%; Score 2194; Length 419;
Best Local Similarity 100.0%;
Matches 419; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
Qy 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
Qy 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
Qy 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
Qy 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
Qy 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
Qy 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
Claims 44-45, 49, 54: Csiszovszki et al 2021 teaches in some embodiments, the polypeptide vaccine comprises at least one sequence from at least two of the following groups: SARS-CoV-2 surface protein, SARS-CoV-2 nucleocapsid protein, SARS-CoV-2 membrane protein and SARS-CoV-2 envelope protein and thus anticipates claims 44-45, 49, 54 (See, col 4 lines 17-35).
Claim 99: Csiszovszki et al 2021 teaches the limitation of claim 99 wherein the at least one nucleic acid comprises at least one heterologous untranslated region selected from at least one heterologous 5'-UTR and/or at least one heterologous 3'-UTR (See, 14, lines 57-67, col 1-21).
Claims 107-108: Csiszovszki et al 2021 teaches a mRNA, self-replicating RNA (reads on self-amplifying RNA) (See, col 14 last para, col 15 lines 1-59).
Claim 116: Csiszovszki et al 2021 teaches at least one nucleic acid is complexed or associated with one or more lipids thereby forming lipid nanoparticles (LNPs) by disclosing the pharmaceutical compositions are encapsulated in a suitable vehicle either nanoparticle, liposomes, microemulsions, micelles, dendrimers and other phospholipid-containing systems (See, col 12 last para).
Claim 147: A Kit or kit of parts, comprising at least one pharmaceutical composition of claim 1 and technical instructions providing information on administration and dosage of the kit components (See, col 12 lines 32-39).
Thus claims 1, 44-45, 49, 54, 99, 107-108, 116 and 147 are anticipated by Csiszovszki et al 2021.
Claim Rejections - 35 USC § 103
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
12. Claims 1, 44, 49, 54-55, 97-99, 107-108, 111, 116 and 147 are rejected under 35 U.S.C. 103 as being unpatentable over Rauch 2018 (WO2018115527A2, 06/28/2018), and further in view of Csiszovszki et al 2021 (US10973909B1, 04/13/2021, with an earlier priority of 04/07/2020 to 16/ 842,669).
Claim 1: Rauch 2018 is directed to mRNA-based vaccines against infections with MERS coronaviruses. Rauch 2018 teaches mRNA comprising at least one coding region, encoding at least one antigenic peptide or protein derived from a Middle East respiratory syndrome coronavirus (MERS coronavirus/MERS-CoV) suitable for use as a vaccine wherein the at least one antigenic peptide or protein comprises a spike protein (S), a spike SI fragment (SI), an envelope protein (E), a membrane protein (M) or a nucleocapsid protein (N) of a MERS coronavirus, or a fragment or variant of any one of these proteins (See, abstract, claims 1-3). The composition is at least one mRNA comprising a pharmaceutically acceptable carrier (see, claim 55).
Rauch 2018 does not teach nucleocapsid protein (N) having a sequence at least 90% identical to the sequence according to SEQ ID No: 15310.
Csiszovszki et al 2021 is directed to a coronavirus vaccine, SARS-CoV-2 vaccine comprising protein or RNA nucleic acid vaccine pharmaceutical composition comprising SEQ ID NO: 123 (See, Col 29 for Nucleocapsid protein SEQ ID NO: 123) has 100% identity with instant SEQ ID NO.: 15310. The polypeptides and vaccines comprise T cell and/or B cell epitopes that are immunogenic in a high percentage of individuals in the human population (see, abstract, Example 1 PolyPEPI-SCoV-2 Vaccine Design corresponds to multivalent vaccine. The structural proteins include the spike (S) protein, the envelope (E) protein, the membrane (M) protein, and the nucleocapsid (N) protein, Example 4).
Query Match 100.0%; Score 2194; Length 419;
Best Local Similarity 100.0%;
Matches 419; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
Qy 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
Qy 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
Qy 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
Qy 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
Qy 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
Qy 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
Claims 44, 49, 54, 99, 107-108, 111 and 147: The disclosures of Csiszovszki et al 2021 that anticipated claims 44, 49, 54, 99, 107-108, 116 and 147 as recited supra are incorporated here in entirety to render obvious claims.
Claim 55: Rauch 2018 teaches pre-fusion stabilization of coronavirus Spike protein (See, WO2018115527A2, page 67 para 1).
Claims 97-98: Rauch 2018 teaches the limitation wherein the at least one RNA coding sequence is a codon modified coding sequence having an increased G/C content by disclosing DNA sequences were prepared by modifying the wild type encoding DNA (reads on RNA sequence for GC content) sequences by introducing a GC-optimized sequence for stabilization, using an in-silico algorithms that increase the GC content of the respective coding sequence (See, WO2018115527A2, page 100, Example 1, page 38 lines 26-40).
Claim 111. Rauch 2018 teaches claim limitation wherein all uracil nucleotides are replaced by pseudouridine (W) nucleotides and/or N1-methylpseudouridine (ml W) nucleotides (See, WO2018115527A2, pages 34- 36, page 35 lines 18-25).
It would have been obvious to one of the ordinary skills before the effective filing date of the claimed invention to modify the prior art teachings of Rauch 2018 with additional teachings of Csiszovszki et al 2021 to incorporate nucleocapsid protein (N) sequence SEQ ID NO: 123 to arrive at the inventions of claim 1 to obtain a pharmaceutical composition comprising RNA (mRNA) encoding nucleocapsid protein (N) having a sequence identical to the instant claimed sequence SEQ ID No.: 15310 to develop the mRNA vaccine for commercial success. There would have been a reasonable expectation of success to develop the claimed mRNA vaccine. The motivation would be to develop an efficacious multivalent mRNA vaccine comprising internal proteins of coronavirus to induce broad cellular T-cell responses (See, Rauch 2018 WO2018115527A2 and Csiszovszki et al 2021, US10973909B1). The motivation would be to develop efficacious mRNA vaccine comprising Nucleocapsid encoding mRNA as a component of multivalent vaccine against coronavirus.
It would have been obvious to modify the combined prior art teachings of Rauch 2018 WO2018115527A2 and Csiszovszki et al 2021, US10973909B1 with additional teachings of Csiszovszki et al 2021 and Rauch 2018 to render obvious the added limitations of claims 44, 49, 54-55, 97-99, 107-108, 111, 116 and 147 with a reasonable expectation of success with amotivation to develop variant inventions to develop an efficacious vaccine composition comprising the mRNA encoding the claimed Nucleocapsid protein having a sequence identical to the instant claimed sequence SEQ ID No.: 15310 to develop the mRNA vaccine for commercial success.
This is analogous to some teaching, suggestions, or motivation in prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 1, 44, 49, 54-55, 97-99, 107-108, 111, 116 and 147. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
13. Claims 45, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Rauch 2018 (WO2018115527A2, 06/28/2018), Csiszovszki et al 2021 (US10973909B1, 04/13/2021, with an earlier priority of 04/07/2020 to 16/ 842,669), as applied to claims 1, 44, 49, 54-55, 97-99, 107-108, 111, 116 and 147 and further in view of Wu et al 2020 (Nature. 2020;579(7798):265-269).
Claims 45, and 47-48: The combined teachings of Rauch 2018 and Csiszovszki et al 2021 rendered obvious claim 44.
However, the combined teachings did not explicitly teach added limitation of claims 45, and 47-48 dependent on claim 44.
Wu et al 2020 disclosed a new coronavirus, SARS-CoV-2, associated with human respiratory disease in China including full length RNA genome sequence and ORFs encoded by mRNA of structural and nonstructural proteins claimed in the instant claims 45, and 47-48 (See, page 266, Fig. 1, entire article).
It would have been obvious to modify the combined prior art teachings of Rauch 2018 WO2018115527A2 and Csiszovszki et al 2021, US10973909B1 with additional teachings of Wu et al 2020 to render obvious the added limitations of claims 45 and 47-48 with a reasonable expectation of success with amotivation to develop a pharmaceutical composition comprising a multivalent Nucleocapsid protein and non-structural protein ORFs encoding mRNA sequences as claimed in claims 45 and 47-48 inventions to develop an efficacious multivalent mRNA vaccine composition as a vaccine for commercial success.
This is analogous to some teaching, suggestions, or motivation in the prior art that would have led one of the ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 45, and 47-48. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
14. Claim 56 is rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Rauch 2018 (WO2018115527A2, 06/28/2018), Csiszovszki et al 2021 (US10973909B1, 04/13/2021, with an earlier priority of 04/07/2020 to 16/ 842,669), as applied to claims 1, 44, 49, 54-55, 97-99, 107-108, 111, 116 and 147 and further in view of Zhang et al 2020 (CN112079906A, 12/15/2020 with an earlier priority of 07/15/2020 to CN202010680911.9A).
Claim 56: The combined teachings of Rauch 2018 and Csiszovszki et al 2021 rendered obvious claim 55.
However, the combined prior art teachings did not explicitly teach the added limitation of claims 56.
Zhang et al 2020 teaches a highly stable novel coronavirus spike protein pre-fusion stabilization of coronavirus spike protein by comprising amino acid substitutions K986P and V987P (See, CN112079906A, claim 1).
It would have been obvious to modify the combined prior art teachings of Rauch 2018 WO2018115527A2 and Csiszovszki et al 2021, US10973909B1 with additional teachings of Zhang et al 2020 on coronavirus spike protein pre-fusion stabilization of spike protein by comprising amino acid substitutions K986P and V987P with a reasonable expectation of success with amotivation to develop a stabilized configuration structure of spike protein to develop a pharmaceutical composition comprising a multivalent stabilized spike protein, Nucleocapsid protein and non-structural protein ORFs encoding mRNA sequences as claimed in claims 56 to develop an efficacious multivalent mRNA vaccine composition as a vaccine for commercial success.
This is analogous to some teaching, suggestions, or motivation in the prior art that would have led one of the ordinary skills to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 56. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
Claim Rejections - 35 USC § 112 (Written Description)
15. 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.
Claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 are 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.
Claims 1, 12 and dependent claims are directed to a pharmaceutical composition comprising nucleic acid comprising RNA coding sequence encoding antigenic peptide or protein from a Coronavirus, wherein the antigenic peptide or protein is a nucleocapsid protein (N) having a sequence at least 90% identical to the sequence according to SEQ ID NO: 15310 (instant claim 1), and at least 85% identical to a N protein encoding nucleic acid sequences selected from SEQ ID NOs: 17187, 19064 and 20941 (instant claim 12). The instant claim 1 SEQ ID NO: 15310 recites an amino acid sequence that has limitation requiring 90% identity (10% variation) in amino acid sequence. The instant claim 12 SEQ ID NOs: 17187, 19064 and 20941 recites the nucleic acid sequences that have limitations requiring 85% identity (15% variation) in nucleic acid sequences. The invention is directed to multivalent nucleic acid vaccine intended to induce immune response against a coronavirus and confer protection and thus implicitly comprise a functional limitation an induction of immune response against a coronavirus. The instant claims 1 and 12 recites broad genus of Nucleocapsid sequence (amino acid or nucleic acid) that has a large degree of claimed variation (10% variation for claim 1 and 15% variation for claim 12). When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claimed genus comprises innumerable number of sequences that arise due to the claimed variation. The specification has not adequately described the species of the genus, nor successfully reduced to practice the variant species of the genus. The claims recite % identity (90% for claim 1 or 85% for claim 12) without disclosing any structure of the variant Nucleocapsid gene. Under BRI the variation can comprise substitutions of amino acids in NP protein encoding sequence or deletion or insertion of amino acid or nucleotide sequences that can affect the B and T cell epitopes and thus immune response (humoral and cellular) against a coronavirus. One of ordinary skills in the art cannot conclude that Applicant was in possession of the innumerable variant species of Nucleocapsid sequences encompassed by the claimed genera. Absent the disclosed positions of variation along the sequence, the skilled artisan would not be able to visualize or otherwise predict, a priori, each individual variant sequence of the Nucleocapsid gene. Thus, it is clear that the breadth of the claimed genus overreaches the Applicant’s contribution.
In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain the structure of the variant Nucleocapsid gene that is required to induce immune response. However, the specification fails to describe any substantive structural limitations as to establish the criteria necessary to design a Nucleocapsid gene nucleic acid or RNA vaccine that is intended to induce protective anti-coronavirus immune response.
The disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). See MPEP 216.
One having ordinary skill in art cannot determine the structures encompassed by the claimed genus. Overall, the claims as currently written are not adequately described and one of ordinary skills in that art would have readily appreciated that Applicant was not in possession of the claimed genus of variant Nucleocapsid sequence at the time of filing.
"The purpose of [the written description requirement] is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163.
The written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.
The legal standard for sufficiency of a patent's (or a specification’s) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the claimed subject matter", Vas-Cath, Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 112 (Scope of Enablement)
16. Claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for 100% identity to the amino acid encoding nucleic acid sequences SEQ ID No.: 15310 (claim 1), SEQ ID NOs: 17187, 19064 and 20941 (claim 12), does not reasonably provide enablement for at least 90% identity (claim 1) 85% identical (claim 12) to the nucleic acid sequences as claimed in instant claims 1 and 12. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The specification does not reasonably provide enablement for the instant claims 1 and 12 pharmaceutical composition(s) comprising, an RNA coding sequence comprising 90% identical to the sequence according to SEQ ID No.: 15310 (claim 1) or the nucleic acid sequence comprising 85% identical to the sequence selected from SEQ ID NOs: 17187, 19064 and 20941 (claim 12). The claims depending on base claim inherit the limitations.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." The factors considered include, but are not limited to: (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill in the art; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims and nature of the invention: Claims 1 and 12 of the claimed invention are drawn to a pharmaceutical composition comprising nucleic acid encoding to a coronavirus antigenic peptide or protein is a nucleocapsid protein (N) having a sequence at least 90% identical to the sequence according to SEQ ID NO: 15310 (claim 1), and at least 85% identical to any one of the nucleic acid sequences selected from SEQ ID NOs: 17187, 19064 and 20941 (claim 12). The claimed nucleocapsid protein (N) encoding nucleic acid sequence comprises a large degree of variation (genus) and thus can comprise a large number of species of variant nucleocapsid protein (N) and thus the claims are very broad. Claims 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 depend on base claim 1. The claims are intended and directed to a functional limitation of induction of protective immune response against a coronavirus.
The level of one of ordinary skills in the art: The required level of skills in art is that of Ph.D. level scientists and medical doctors (D.O. and/or M.D.).
Amount of direction and existence of working examples: The instant application does not represent even one example comprising a variant nucleocapsid protein (N) pharmaceutical composition indicating positions and residues in the variant sequences as compared to the reference sequences SEQ ID NO: 15310 (claim 1), and SEQ ID NOs: 17187, 19064 and 20941 (claim 12).
Working Example: The instant application does not represent even one example comprising a variant nucleocapsid protein (N) pharmaceutical composition indicating positions and residues in the variant sequences as compared to the reference sequences SEQ ID NO: 15310 (claim 1), and SEQ ID NOs: 17187, 19064 and 20941 (claim 12) reduced to practice inducing reasonably protective immune response against a coronavirus. The instant disclosure does not offers reasonable guidance or direction.
State of the prior art and unpredictability in the art: The prior art (See, Rahman et al 2020 on Evolutionary dynamics of SARS-CoV-2 nucleocapsid (N) protein and its
consequences) teaches a large number of variations in the Nucleocapsid protein encoding gene of a coronavirus (SARS-CoV-2). It is not clear to one of the ordinary skills which variations in the nucleocapsid protein (N) sequence are claimed in the instant claims 1, 12 and dependent claims and how the mutations/variations could affect/influence induction of a protective immune response against a coronavirus.
Quantity of experimentation needed: At a minimum the art teaches that a skilled artisan would consider the predictive function of a variant nucleocapsid protein (N) sequence.
Thus, one of skills in the art would neither expect nor predict the appropriate function of a variant nucleocapsid protein (N) sequence for induction of protective immune response.
Any and all enablement of the claimed variant nucleocapsid protein (N) sequence must therefore come from the instant disclosure. The claims are clearly not enabled to their full scope. Moreover, the claims not containing elements critical or essential to the practice of the invention, such as specific amino acid residue variation as compared to the reference sequences of claims 1 and 12, are not enabled by the disclosure to induce protective immune response using variant nucleocapsid protein (N) against a coronavirus. In this context, see, claims that contain materials demonstrated not to bind to the critical element of the invention are also not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
For the reasons discussed above, “undue and unreasonable experimentation” is required to practice the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. It would take undue trials and errors to practice the claimed invention in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims.
Therefore, the instant disclosure is not enabled for any variant nucleocapsid protein (N) as presently written but rather is only enabled to the claimed SEQ ID NO: 15310, and SEQ ID NOs: 17187, 19064 and 20941 with 100% sequence identity. Thus, claims 1, 12 and dependent claims limitations that do not further limit the nucleocapsid protein (N) identity requirement to 100% are not enabled. This includes elected claims 1, 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147.
Allowable Subject Matter
17. Claim 12: The nucleic acid sequence encoding a nucleocapsid protein (N) being identical (100% sequence identity) to any one of the nucleic acid sequences selected from SEQ ID NOs: 17187, 19064 and 20941 are free of prior art.
The prior art teaches Query Match 76.3% and Best Local Similarity 78.4% to the instant claim 12 SEQ ID NO: 17187, Query Match 62.8% and Best Local Similarity 78.5% to the instant claim 12 SEQ ID NO: 19064, and Query Match 65.1% and Best Local Similarity 78.5% to the instant claim 12 SEQ ID NO:20941.
18. Claims 12, 44, 45, 47-49, 54-56, 97-99, 107, 108, 111, 116, and 147 are objected to as being dependent upon a rejected base claim (claim 1) but would be allowable if rewritten in independent form including all of the limitations of the base claim and limitations from claim 2 on being identical (100% sequence identity) to the SEQ ID NOs: 17187, 19064 and 20941 and any other limitations from the dependent claims.
19. Relevant Prior Art:
Monath et al 2004 (WO2004091524A, 10/28/2004). Disclosed is a vaccine and method for inducing an immune response to a human coronavirus that is the causative agent of Severe Acute Respiratory Syndrome (SARS) in a patient, comprising a nucleic acid sequence encoding said vaccine comprising a spike protein or a nucleocapsid protein of said virus, or an immunogenic fragment of either of these proteins, and a pharmaceutically acceptable carrier or diluent.
Mosharraf et al 2021 (US20210299244A1, 09/30/2020 with a priority to 03/17/2020). Disclosed the immunogenic composition comprising the nucleic acid includes at least a sequence of ribonucleic acid (RNA), mRNA, nanoparticle, wherein the antigen comprises a nucleic acid encoding a protein from a coronavirus.
Peng et al 2020 (CN111218458A, 06/02/2020). mRNAs encoding SARS-CoV-2 virus antigen and vaccine and preparation method of vaccine.
Sutter et al 2016. (WO2016116398A1, 07/28/2016). A novel nucleic acid vaccine against the middle east respiratory syndrome coronavirus (MERS-CoV).
Bennett et al 2021 (WO2021159130A2, 08/12/2021). Coronavirus RNA vaccines and methods of use.
Conclusion
20. No Claim is allowed.
21. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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 by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, 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.
/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
Prosecution Insights