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 .
Specification
The disclosure is objected to because of the following informalities: SEQ ID NO. # should read SEQ ID NO: #.
Appropriate correction is required.
Claim Objections
Claims 4-8, 15, 19, 21, and 23 are objected to because of the following informalities: SEQ ID NO. # should read SEQ ID NO: #. 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.
Claims 13-16, 18-19, and 23 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 some embodiments, does not reasonably provide enablement for all embodiments.
The breadth of claims 13-16, 18-19, and 23 encompasses a method that employ a vaccine composition for viruses belonging to the family Coronaviridae, the vaccine comprising a polynucleotide coding for at least one protein of a virus belonging to the family Coronaviridae or for at least one portion of said protein. Embodiments that use the full spike glycoprotein or the receptor binding domain (RBD) of the spike glycoprotein are enabled as a vaccine having the claimed effect of preventing viral infection/pathology. Embodiments that use fragments of the spike glycoprotein or RBD are not enabled as vaccines having the claimed effect of preventing viral infection/pathology.
The structure provided for the protein is a fragment of no particular length of a protein of a virus belonging to the family Coronaviridae. The specification provides two examples of a Coronaviridae viral protein, the SARS-CoV-2 spike glycoprotein and SARS-CoV-2 RBD (Table 1). The Office does not doubt that portions of these proteins can be produced, but whether they have the claimed functions of preventing viral infection/pathology.
Chen, et al. (Curr Trop Med Rep. 2020 Mar 3; 7(2):61-64, hereinafter “Chen”) provides a review of the state of the art in SARS-CoV-2 vaccines. SARS-CoV-2 vaccines that use the spike glycoprotein or RBD do not use only portions of these proteins, rather the intact proteins are used (pg. 62 column 2).
In view of the breadth of the claims, the limited teachings of the specification and working examples regarding fragments of the spike glycoprotein and RBD, the state of the art, and the low predictability with regard to protection using portions of the spike glycoprotein or RBD for achieving protection, it would require undue experimentation to practice the claimed methods. Amendment of the claims to require the protein to comprise the spike glycoprotein or RBD would overcome this rejection.
Claims 1-8, 10-11, 17, and 20-22 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.
The written description requirement for a claimed genus 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 inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he 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.' (internal quotation marks omitted).").
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, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). 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. 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.”
Instant claims 1-8, 10-11, 17, and 20-22 broadly encompasses a vaccine composition comprising at least one protein of a virus belonging to the family Coronaviridae or for at least one portion of said protein. A vaccine composition inherently requires the function of immune stimulation/modulation.
Instant claims 2-3 and 20 further recite that the protein is the full-length spike glycoprotein from SARS-CoV, MERS-CoV, or SARS-CoV-2 or a portion of the spike glycoprotein. Instant claims 4-6 and 18 further recite that the protein is coded for by a nucleic acid sequence at least 80% identity with, at least 90% identity with, or consisting within SEQ ID NO: 1 or 2 or a portion of the sequence. Instant claims 7-8, and 21 further recite that the protein has at least 80% identity with, at least 90% identity with, or consists within SEQ ID NO: 3 or 4 or a portion of the sequence.
The Specification has failed to sufficiently describe the structural features that must be retained by the members of the claimed genus as to establish a structure-function relationship with respect to the vaccine and immune stimulation.
“[A]t least one portion of said protein” encompasses a large pool of variant polypeptides when accounting for each protein of any virus belonging to the family Coronaviridae as well as a portion of each of these proteins consisting of a single amino acid up to a full-length protein consisting of hundreds of amino acids. “[A] sequence that is at least [80%] 90% identical to SEQ ID NO: 1 or [2] also encompasses a large pool of sequences as allowing for changes in 10-20% of the amino acid residues allows for many proteins. Lastly, “a sequence that consists in SEQ ID NO: 1 or [2]” also allows for a large pool of variants from a single amino acid to any combination of trimers within the sequence up to the full-length sequence.
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences, the Specification has only adequately described and successfully reduced to practice specific NA sequences (SEQ ID NOs: 1 and 2) and AA sequences (SEQ ID NOs: 3 and 4). As such, the Specification reasonably demonstrates that Applicant was in possession of vaccine compositions with SEQ ID NOs: 1-4. However, this is not representative of the extremely large genus of sequences claimed since these sequences only encompass SARS-CoV-2 spike glycoprotein and RBD and not the innumerable sequences contained within a genus of sequences comprising at least one portion of a protein of a virus belonging to a Coronaviridae family.
The data generated for SEQ ID NOs: 1-4 described in the Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of variants and fragments because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials consisting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
As discussed above, Chen provides a review Coronaviridae proteins that can be used for vaccine compositions, these include the spike glycoprotein and RBD, and not portions of these proteins. While Applicant may have possession of portions of these proteins, as the portions have not been shown to stimulate/modulate the immune response, these fragments would not be considered vaccines.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
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 4-8, 16-17, 19, and 21-23 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.
The term “a sequence” in claims 4-8, 16-17, 19, 21, and 23 is a relative term which renders the claim indefinite. The term “a sequence” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, “A sequence that is at least 90% identical” may include sequences 10 residues long with 9/10 residues being identical to the claimed sequence. “[The] sequence” is the appropriate terminology which would fix the indefiniteness of the claims.
Claim 22 recites the limitation "according to claim 9" in the preamble. There is insufficient antecedent basis for this limitation in the claim as claim 9 has been cancelled. For the purposes of compact prosecution claim 22 will be interpreted as dependent on claim 10.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this Office Action. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection and art may be applied in a subsequent 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 1-3, 7, 10, 17-18, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, et al. (Process Biochemistry, Volume 87, December 2019, Pages 164-173 NPL-IDS, filed, 09/11/2023, hereinafter “de Oliveira”) and in further view of Chang, et al. (US 2012 0288524 A1 US-IDS, filed, 09/11/203, hereinafter “Chang”), and Fu, et al. (CN 112079907 A FOR-IDS, filed, 09/11/2023, hereinafter “Fu”).
Regarding claim 1, de Oliveira teaches LEXSY, a Leishmania tarentolae system used to express viral proteins (Abstract and Table 4). de Oliveira does not teach expression of Coronaviridae proteins or vaccine compositions.
However, Chang teaches using Leishmania in a vaccine composition to deliver proteins (Abstract). 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 the teachings of de Oliveira for the LEXSY system with the teachings of Chang for a Leishmania vaccine composition. De Oliveira provides motivation by teaching that the LEXSY system can be used for vaccine development (Pg. 171 column 1). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira and Chang because they both teach Leishmania cells expressing non-native proteins. de Oliveira and Chang do not teach that protein is a Coronaviridae protein.
However, Fu teaches using a bacterial (E. coli) system to produce a Coronaviridae protein (Abstract, Contents of the Invention, and SEQ ID NO:2). 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 the teachings of de Oliveira and Chang for a Leishmania cell expressing viral proteins vaccine composition with the teachings of Fu for the viral protein expressed being a Coronaviridae protein. de Oliveira provides motivation by teaching that L. tarentolae advantageously allows for mammalian-type post-translational modification of proteins over the E. coli system (pg. 165 column 2). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, and Fu because they all teach expression systems expressing non-native proteins.
Regarding claim 2, 3, and 20, Fu teaches that the protein is the SARS-CoV-2 spike glycoprotein (Contents of the Invention and SEQ ID NO: 2).
Regarding claim 7and 21, Fu teaches a polypeptide sequence which consists within SEQ ID NO: 4 (SEQ ID NO: 2).
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Regarding claims 10 and 22, de Oliveira teaches that the cell is Leishmania tarentolae (Abstract).
Regarding claim 17, de Oliveira teaches a host cell belonging to the genus Leishmania comprising a polynucleotide coding for a viral protein (Abstract and Table 4). Fu teaches the polynucleotide of instant claim 4 expressed in a bacterial expression system (Contents of the Invention and SEQ ID NO: 2).
Regarding claim 18, Chang teaches preparing a vaccine composition of a modified Leishmania cell to express non-native proteins and that the vaccine comprises those cells and an acceptable carrier (¶0098). Fu teaches that the non-native protein is a Coronaviridae protein (Contents of the Invention and SEQ ID NO:2).
Accordingly, the inventions were 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 4-5 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, Chang, and Fu as unpatentable over claims 1-3, 7, 10, 17-18, and 20-22 above, and further in view of Fuglsang (Protein Expression and Purification Volume 31, Issue 2, October 2003, Pages 247-249).
Regarding claim 4-5, Fu teaches a polynucleotide sequence that encodes for the SARS-CoV-2 spike glycoprotein (Contents of the Invention and SEQ ID NO: 1). de Oliveira, Chang, and Fu do not teach the exact sequence of SEQ ID NO:1 or 2. However, Fuglsang teaches codon optimization involves producing the same protein (in this case instant SEQ ID NO: 4 and Fu reference SEQ ID NO: 2) but increasing yield by substituting rare codons (Abstract).
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 the teachings of de Oliveira, Chang, and Fu for a Leishmania vaccine expressing a Coronaviridae protein with the teachings of Fuglsang for codon optimization to improve protein yield to obtain a sequence with over 90% sequence identity to instant SEQ ID NO: 2. Fuglsang provides motivation by teaching that optimizing codons improves protein yield by using rare codons (Abstract). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, Fu, and Fuglsang because they all teach protein production.
Regarding claim 19, Chang teaches preparing a vaccine composition of a modified Leishmania cell to express non-native proteins and that the vaccine comprises those cells and an acceptable carrier (¶0098). Fu teaches that the non-native protein is a Coronaviridae protein (Contents of the Invention and SEQ ID NO:2) encoded by SEQ ID NO 1. Fuglsang teaches that codon optimization increases protein yield.
Accordingly, the inventions were 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 6 is rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, Chang, Fu, and Fuglsang as unpatentable over claims 1-5, 7, 10, 17-19, and 20-22 above, and further in view of Shemesh, et al. (Genomics Proteomics Bioinformatics. 2010 Oct 21;8(3):180–189, hereinafter “Shemesh”).
As discussed above, claims 1 and 4 were rendered obvious over de Oliveira, Chang, Fu, and Fuglsang.
Regarding claim 6, Fu teaches a polynucleotide sequence that encodes for the SARS-CoV-2 spike glycoprotein (Contents of the Invention and SEQ ID NO: 1).
de Oliveira, Chang, and Fu do not teach the exact sequence of SEQ ID NO:1 or 2. However, Fuglsang teaches codon optimization involves producing the same protein (in this case instant SEQ ID NO 4 and Fu reference SEQ ID NO 2) but increasing yield by substituting rare codons (Abstract).
de Oliveira, Chang, Fu, and Fuglsang do not teach the first 6 nucleotides that encode Met and Ala. However, Shemesh teaches adding Met-Ala at the beginning of a protein sequence which in turn would add corresponding nucleotides to the NA sequence (Introduction ¶2).
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 the teachings of de Oliveira, Chang, Fu, and Fuglsang for a codon optimized Leishmania vaccine composition expressing the SARS-CoV-2 RBD protein with the teachings of Shemesh for adding Met-Ala at the beginning of amino acid sequences. Shemesh provides motivation by teaching that the addition of these amino acids provides stability and facilitates proper N-terminal processing (Introduction ¶1)). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, Fu, Fuglsang, and Shemesh because they all teach protein expression.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, Chang, and Fu as unpatentable over claims 1-3, 7, 10, 17-18, and 20-22 above, and further in view of Shemesh.
As discussed above, claims 1 and 7 were rendered obvious over de Oliveira, Chang, and Fu.
Regarding claim 8, Fu further teaches an amino acid sequence that has 100% sequence identity to aa resides 3-275 of instant SEQ ID NO: 4 (reference SEQ ID NO: 2). de Oliveira, Chang, and Fu do not teach aa residues 1 and 2, Methionine and Alanine. However, Shemesh teaches adding Met-Ala at the beginning of a protein sequence (Introduction ¶2).
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 the teachings of de Oliveira, Chang, and Fu for a Leishmania vaccine composition expressing the SARS-CoV-2 RBD protein with the teachings of Shemesh for adding Met-Ala at the beginning of amino acid sequences. Shemesh provides motivation by teaching that the addition of these amino acids provides stability and facilitates proper N-terminal processing (Introduction ¶1)). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, Fu, and Shemesh because they all teach protein expression.
Accordingly, the inventions were 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 13-16 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, Chang, and Fu as unpatentable over claims 1-3, 7, 10-, 17-18, and 20-22 above, and further in view of Filinova (WO 2009046984 FOR-IDS, filed, 09/11/2023).
As discussed above, de Oliveira, Chang, and Fu teach the Coronaviridae vaccine composition of claim 1.
Regarding claim 13, the references do not teach using the vaccine composition for preventing a viral infection. However, Filinova teaches a method for preventing a viral infection by administering a Leishmania vaccine (Abstract).
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 the teachings of de Oliveira, Chang, and Fu for a Leishmania vaccine composition for treating Coronaviridae with the teachings of Filinova for a method of treating a viral disease with a Leishmania vaccine. Filinova provides motivation by teaching that the virus that the viral protein used in the vaccine composition is from is the viral disease being treated (Abstract). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, Fu, and Filinova because they all teach protein expression.
Regarding claims 14-16 and 23, Fu teaches the protein being a SARS-CoV-2 protein with more than 90% identity with instant SEQ ID NO:4 (Contents of the Invention and SEQ ID NO:2)
Accordingly, the inventions were 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 11 is rejected under 35 U.S.C. 103 as being unpatentable over de Oliveira, Chang, and Fu as unpatentable over claims 1-3, 7, 10 17-18, and 20-22 above, and further in view of Ferreccio, et al. (The Journal of Infectious Diseases, Volume 159, Issue 4, April 1989, Pages 766–769, hereinafter “Ferreccio”).
As discussed above, de Oliveira, Chang, and Fu teach the Coronaviridae vaccine composition of claim 1.
Regarding claim 11, Chang further teaches the vaccine can be delivered orally or topically (Vaccine-Candidate Delivery by Leishmania). de Oliveira, Chang, and Fu do not teach the form of the oral vaccine. However, Ferreccio teaches that oral vaccines may be capsules (Title). 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 the teachings of de Oliveira, Chang, and Fu for a Leishmania vaccine composition for treating Coronaviridae with the teachings of Ferreccio for a capsule oral vaccine. Ferreccio provides motivation by teaching that oral vaccines allow for higher incidence in vaccine compliance (abstract). One of skill in the art would have had a reasonable expectation of success at combining de Oliveira, Chang, Fu, and Ferreccio because they all teach proteins.
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