DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-15 were pending in the present application. By virtue of a Preliminary Amendment, filed by Applicant on 18 January 2023, claims 1-15 were amended and claims 16-19 were added. Therefore, claims 1-19 are now pending and currently under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application
filed in NL on 20 July 2020.
The instant application filed on 18 January 2023 is a 371 of PCT/NL2021/050461 filed 20 July 2021. In addition, the instant application claims foreign priority of NL2026094
filed 20 July 2020 and which finds full support for the instant claims. Therefore, the effective filing date of the instant application is 20 July 2020.
Information Disclosure Statement (IDS)
The IDSs (2) filed on 18 January 2023 and 08 September 2023 have been considered by the examiner. Signed copies are enclosed.
Applicant is reminded of their duty to disclose to the Office all information known to the
person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach
individual associated with the filing and prosecution of a patent application has a duty of candor
and good faith in dealing with the Office, which includes a duty to disclose to the Office all
information known to that individual to be material to patentability as defined in this section.”
Claim Rejections - 35 USC § 112(a)
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, 5, and 16-17 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 a composition comprising a peptide and/or nucleic acid molecule encoding the peptide where the peptide is comprised of the fusion peptide, the HR1 heptad repeat, or the HR2 heptad repeat of the S protein of HCoV-NL63, HCoV-OC43, HCoV-229E, or HCoV-HKU1, does not reasonably provide enablement for a method of increasing immunity in a human against coronavirus(es) by administering a peptide and/or nucleic acid molecule encoding the peptide wherein the peptide comprises at least part of the S2 ectodomain of the S protein from HCoV-NL63, HCoV-OC43, HCoV-229E, or HCoV-HKU1. 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/or use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims
The claims are drawn to a method of increasing immunity in a human against at least two different coronaviruses. The method comprises administering intranasally to a human a composition comprising a peptide, or nucleic acid molecule encoding the peptide, wherein the peptide comprises at least a part of the S2 ectodomain of the S protein from at least one human coronavirus selected from: HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1. In its broadest reasonable interpretation, instant claim 1 is drawn to a method of increasing immunity in a human against at least two different coronaviruses by intranasally administering part of the S2 ectodomain of the spike protein from HCoV-NL63, HCoV-OC43, HCoV-229E, and/or HCoV-HKU1. Essentially, instant claim 1 is claiming a method of increasing immunity against at least two different coronaviruses, that can be any two coronaviruses including non-human coronaviruses, by administering a peptide that could contain only five amino acid residues of the S2 ectodomain of the spike protein from HCoV-NL63, HCoV-OC43, HCoV-229E, and/or HCoV-HKU1. See specification p. 11: “[p]referably, peptides comprising between 5-50, more preferably between 12-20 amino acids of the S2 ectodomain are provided” (p. 11, lines 22-23).
State of the art/Predictability of the art
The specification details “increasing immunity” as an individual’s immune response against a particular antigen (p. 5, lines 27-28). Increased immunity can lead to increased resistance to infection or may improve an individual’s ability to fight infection (e.g., infection may be cleared before symptoms arise or symptoms experienced are milder) (p. 5, lines 28-31; p. 6, lines 5-35; p. 7 lines 1-8).
Applicant has further detailed references containing exemplary full-length HCoV-NL63 sequences with >98% sequence identity (p. 9, lines 4-25); genomic sequences of full-length HCoV-229E with >99% sequence identity (p. 9, lines 27-34; p. 10, lines 1-10); genomic sequences of full-length HCoV-HKU1 with >99% sequence identity (p. 10, lines 11-23); and genomic sequences of full-length HCoV-OC43 with >98% sequence identity (p. 10, lines 25-34; p. 11, lines 1-3). Applicants further state the spike proteins of the common human coronaviruses have been described by prior art and the S2 ectodomains are also known (p. 11, lines 5-6).
Prior art indicates the following with regard to the S2 ectodomain of corresponding human coronaviruses:
HCoV-NL 63
The entire S2 ectodomain is located at residues 718-1356 aa (639 total aa residues)1
The HR1 heptad repeat is located at residues 947-1066 aa (120 total aa residues)2
The HR2 heptad repeat is located at residues 1211-1307 aa (96 total aa residues)3
The fusion peptide is located at residues 933-953 aa (21 total aa residues)4
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571
1521
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HCoV-229E
The entire S2 ectodomain is located at residues 629-1170 aa (542 total aa residues)5
The HR1 heptad repeat is located at residues 764-883 aa (120 total aa residues)6
The HR2 heptad repeat is located at residues 1028-1124 aa (96 total aa residues)7
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660
1528
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HCoV-OC43
The entire S2 ectodomain is located at residues 759-1353 aa (594 total aa residues)8
The HR1 heptad repeat is located at residues 764-883 aa (120 total aa residues)9
The HR2 heptad repeat is located at residues 1028-1124 aa (96 total aa residues)10
Fusion peptide 1 is located at residues 904-925 aa (22 total aa residues)11
Fusion peptide 2 is located at residues 923-943 aa (21 total aa residues)12
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718
1514
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HCoV-HKU1
The entire S2 ectodomain is located at residues 757-1356 aa (600 total aa residues)13
The HR1 heptad repeat is located at residues 981-1086 aa (105 total aa residues)14
The HR2 heptad repeat is located at residues 1229-1312 aa (83 total aa residues)15
Fusion peptide 1 is located at residues 905-926 aa (22 total aa residues)16
Fusion peptide 2 is located at residues 924-944 aa (21 total aa residues)17
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653
1530
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Greyscale
While the prior art discloses the structure of the S2 ectodomain of different strains of HCoV, the art does not disclose which aspect of the structure, with as little as 5 amino acid residues, is necessary to increase immunity in a human subject.
Working Examples
The disclosure does not provide any working examples of a method or composition used to increase immunity in a human (or animal) subject. The closest disclosure is on page 19, where Applicant describes a general protocol for future experimentation (p. 19, lines 15-25).
Guidance in the Specification
The specification is silent regarding which aspects of the S2 ectodomain are necessary to increase immune response in a human subject. In fact, the specification discloses the peptide need only contain 5 amino acid residues without any further guidance (p. 11, lines 22-23).
Amount of Experimentation Necessary
In view of the breadth of the claims, the nature of the invention, the state of the art, the lack of working examples and limited guidance in the specification, and the low level of predictability, it would require undue experimentation for one skilled in the art to make and use the claimed methods.
Claim Rejections - 35 USC § 112(b)
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 5, 16, and 17 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.
Claim 5 recites the limitation “[t]he composition” in claim 1. However, claim 1 is drawn to a method, not a composition. Therefore, there is insufficient antecedent basis for this limitation in claim 5. Claim 17, which depends from claim 5, also recites the limitation “[t]he composition.” Therefore, there is also insufficient antecedent basis for this limitation in claim 17.
Claim 16 is rejected as being indefinite because claim 16 recites the limitation: “wherein at least one of the coronaviruses is selected from SARS-CoV-1, MERS-CoV, and SARS-CoV-2.” It is unclear whether this limitation pertains to: 1) the method of increasing immunity in a human individual against at least two different coronaviruses; 2) the peptide comprising at least a part of the S2 ectodomain of the S protein from at least one human coronaviruses; or 3) both.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2-4, 9-15, and 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon judicial exception without significantly more. The claims recite a composition which, in their broadest reasonable interpretation, are drawn to naturally occurring peptides and nucleic acids encoding the same. The claims do not integrate the naturally occurring product into a practical application because they do not rely on or use the product in any additional steps or structures. Additionally, the claims do not recite elements beyond the judicial exception that amount to significantly more, because the claims do not recite any elements beyond the exception itself.
The claims are drawn to a composition comprising a peptide, or nucleic acid encoding the peptide, where the peptide comprises at least a part of the S2 ectodomain of the S protein from a human coronavirus. The specification is silent on a method to produce this composition and only indicates that in some embodiments, the peptide is synthetic (p. 13, line 6). The current claims are not directed to a variant of the peptide or indicate any changes are made apart from the limitation that the peptide comprises “at least part of the S2 ectodomain of the S protein.” Without any evidence to the contrary, the peptide function and structure would not be markedly different than the naturally occurring peptide and therefore, the claimed invention does not have markedly different characteristics from what exists in nature. See, e.g., MPEP 2106, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013); Roche Molecular System, Inc. v. CEPHEID, 905 F.3d 1363, 1371, 128 USPQ2d 1221, 1227 (Fed. Cir. 2018).
Accordingly, the claims are directed to a judicial exception. Because the claim does not include any additional features that could add significantly more to the exception, the claim does not qualify as eligible subject matter under 35 U.S.C §101.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 2, 4, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xia (“A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike,” published: 10 April 2019).
Xia teaches peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibits broad fusion inhibitory activity against multiple HCoVs (abstract). “EK1,” the optimized form of OC43-HR2P, shows substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties (abstract).
Regarding instant claim 2, Xia teaches a pharmaceutical composition administered to mice.
A pharmaceutical composition for increasing immunity in a human individual against a highly pathogenic coronavirus, said composition comprising a peptide and/or nucleic acid molecule encoding the peptide, said peptide comprising at least a part of the S2 ectodomain of the S (spike) protein from at least one HCoV selected from HCoV-OC43: “Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-43, exhibited broad fusion inhibitory activity against multiple HCoVs” (abstract).
Regarding instant claim 4, Xia teaches a pharmaceutical composition administered to mice.
The composition of claim 2, wherein the peptide comprises the HR2 repeat of the S protein: “Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-43, exhibited broad fusion inhibitory activity against multiple HCoVs” (abstract).
Regarding instant claim 9, Xia teaches a pharmaceutical composition administered to mice.
The composition of claim 2, wherein the composition is formulated for intranasal delivery: “To investigate the preclinical potential of the EK1 peptide, we administered it via an intranasal route…” (p. 5).
Therefore, as evidenced above, Xia anticipates that which is claimed in instant claims 2, 4, and 9.
Claims 2, 4, 6, and 9 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Joyce (WO 2021/178971; published: 10 September 2021; effective filing date - finds full support in 62/986,522 filed on 06 March 2020 and 63/038,600 filed on 12 June 2020).
Joyce discloses vaccines for treating or preventing coronavirus infections (abstract). Joyce teaches various embodiments of nanoparticles comprising a fusion protein that is a nanoparticle-forming peptide and at least one antigenic coronavirus peptide ([0008]). The antigenic coronavirus peptide can be a stabilized extracellular spike -S2P domain of a coronavirus ([0008]), may comprise 2-10 coronavirus peptides ([0012]), and may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]). See also Joyce p. 298-299, claims 1 and 9.
Regarding instant claim 2, Joyce claims the following coronavirus vaccine composition:
A nanoparticle comprising a fusion protein that further comprises a nanoparticle-forming peptide and at least one antigenic coronavirus peptide selected from a stabilized extracellular spike S-2P domain of a coronavirus (claim 1).
Wherein the antigenic coronavirus is isolated or derived from a coronavirus selected from HCoV-OC43, HKU-1, or NL63 (claim 9).
A vaccine comprising the nanoparticle of any one of claims 1-13 (claim 14).
Regarding instant claim 4, Joyce claims the following coronavirus vaccine composition:
A nanoparticle comprising a fusion protein that further comprises a nanoparticle-forming peptide and at least one antigenic coronavirus peptide selected from a stabilized extracellular spike S-2P domain of a coronavirus (claim 1). Since the antigenic coronavirus peptide, as claimed, could include a full-length coronavirus peptide from the S2 domain under its broadest reasonable interpretation, this would thereby naturally include the fusion peptide, the HR1 heptad repeat, or the HR2 heptad repeat.
Regarding instant claim 9, Joyce claims the following coronavirus vaccine composition:
“The disclosed vaccines can be formulated for intranasal administration” ([0150]). See also ([0152], [0260]).
Therefore, as evidenced above, Joyce anticipates that which is claimed in instant claims 2, 4, 6 and 9.
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, 10-12, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Xia (“A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike,” published: 10 April 2019).
The teachings of Xia are discussed above. Regarding instant claims 1, 10-12, 16, and 19:
Xia assessed the protective effect of EK1 in vivo on OC43 and MERS-CoV infection mouse models (p. 5). Xia formulated the EK1 peptide derived from MERS-CoV HR2 repeats (p. 3). Xia found EK1 showed potent and broad inhibitory activity against MERS-CoV, SARS-CoV, and OC 43 (p. 3; instant claim 10, 16, and 19). Xia administered the EK1 peptide via an intranasal route, assessed its distribution within the respiratory tract and found that EK1 (intranasal) can be widely distributed in the whole respiratory tract, and further found that intranasal administration of EK1 could be beneficial for multiorgan infection or systemic infection of multiple HCoVs (p. 5; instant claims 1, and 10-12). In addition, Xia treated newborn mice with EK1 at a dose of 5 mg/kg or with PBS 30 minutes before or after challenge with HCoV-OC43 and found the final survival rate of mice in the EK1 prophylactic and therapeutic groups was 100 and 66.7% respectively (p. 5). To evaluate the prophylactic and therapeutic potentials of EK1 against MERS-CoV infection, Xia treated mice with 200 µg of EK1 or with PBS 30 minutes before or after challenge with MERS-CoV and found the survival rates in the EK1 prophylactic and therapeutic groups was 100 and 75 % respectively (p. 5). Together, Xia suggests, these results indicate the peptide EK1 has broad and potent prophylactic and therapeutic efficacy against HCoV infections (p. 5).
Xia teaches circulating HCoVs pose a potential threat to humans and the availability of HCoV-specific drugs with broad-spectrum inhibitory activity is therefore important for the prevention and control of a future HCoV epidemic (p. 10). The EK1 fusion inhibitor peptide, tested by Xia on mice, has potent and broad inhibitory activity against multiple HCoV infections (p. 10). EK1, through nasal administration, exhibited effective and broadly anti-HCoV activity with a satisfactory safety profile in vivo therefore making it a promising candidate for further development against multiple HCoVs, especially for use in infants, elderly, and immunocompromised populations (p. 10).
Therefore, while Xia does not explicitly teach a method of increasing immunity in human subjects by administering the EK1 peptide, Xia does teach the effects of the peptide administration in mice and extrapolates the experimental data to human populations (“EK1 through nasal administration…is a promising candidate for further development as an antiviral agent against infection of multiple HCoVs, especially for use in infants and the elderly, as well as immunocompromised patients.” p. 10). Furthermore, one of ordinary skill in the art would know mice are model organisms to study human disease.
In addition, Xia does not explicitly teach the composition induces an immune response in the subject. However, because Xia administered an identical composition via an identical administration route as what is currently claimed, the immune response of the subject is an inherent property. See MPEP 2112 (II), (III).
Xia teaches embodiments that correspond to the currently claimed limitations in instant claims 1, 10-12, 16, and 19. As such, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the disclosed embodiments of Xia to
arrive at the claimed invention. One of ordinary skill, armed with the disclosed embodiments of
Xia, could easily arrive at the currently claimed invention with a predicted success because
Xia teaches the disclosed compositions and methods as being successful in inoculating a
subject against coronavirus.
Claims 1, 3, 5-8, 10-16 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Joyce (WO 2021/178971; published: 10 September 2021; effective filing date - finds full support in 62/986,522 filed on 06 March 2020 and 63/038,600 filed on 12 June 2020).
Joyce discloses vaccines for treating or preventing coronavirus infections (abstract). Joyce teaches various embodiments of nanoparticles comprising a fusion protein that is a nanoparticle-forming peptide and at least one antigenic coronavirus peptide ([0008]). The antigenic coronavirus peptide can be a stabilized extracellular spike -S2P domain of a coronavirus ([0008]), may comprise 2-10 coronavirus peptides ([0012]), and may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
Therefore, regarding instant claim 1, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
Method of increasing immunity in a human individual against at least two different coronaviruses: “In some embodiments, the disclosed vaccines may provide a broad-spectrum treatment and/or prevention for multiple different types of coronaviruses such as MERS-CoV, SARS-CoV and/or SARS-CoV-2” ([0107]); “The "beads on a string" concept can be used to create a nanoparticle with antigenic components from multiple coronaviruses such as SARS-CoV-2, SARS-CoV-1, HKU-1, MERSCoV, 229E, NL63, OC43, or related coronaviruses…these embodiments can be utilized to create a pan-β-coronavirus vaccine, or pan-coronavirus vaccine…beads comprised of different antigenic sequences can be provided together on a single “string” (i.e., in a single construct) to elicit broad immune responses against coronaviruses ([0141]).
Administering intranasally to the human individual: “In specific embodiments, the subject, individual, or patient is a human” ([0102]); “The disclosed vaccines can be formulated for intranasal administration” ([0150]).
A composition comprising at least a part of the S2 ectodomain of the S (spike) protein from at least one HCoV selected from HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1: “At least one antigenic coronavirus peptide selected from…a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof…” ([0008]); “The antigenic coronavirus peptide may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
Regarding instant claims 11 and 12, Joyce discloses the following embodiments of the coronavirus vaccine composition:
A pharmaceutical composition: “Pharmaceutical compositions of the present disclosure include vaccines comprising nanoparticles as disclosed herein” ([0149]).
For increasing immunity in a human individual against a highly pathogenic coronavirus: “In specific embodiments, the subject, individual, or patient is a human” ([0102]); “The "beads on a string" concept can be used to create a nanoparticle with antigenic components from multiple coronaviruses such as SARS-CoV-2, SARS-CoV-1, HKU-1, MERSCoV, 229E, NL63, OC43, or related coronaviruses…these embodiments can be utilized to create a pan-β-coronavirus vaccine, or pan-coronavirus vaccine…beads comprised of different antigenic sequences can be provided together on a single “string” (i.e., in a single construct) to elicit broad immune responses against coronaviruses” ([0141]).
A composition comprising at least a part of the S2 ectodomain of the S (spike) protein from at least one HCoV selected from HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1: “At least one antigenic coronavirus peptide selected from…a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof…” ([0008]); “The antigenic coronavirus peptide may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
A method for increasing immunity in a human individual against one or more highly pathogenic coronaviruses, the method comprising administering to the human individual the composition of claim 2: “In specific embodiments, the subject, individual, or patient is a human” ([0102]).
The method of claim 11, wherein the composition is administered intranasally: “The disclosed vaccines can be formulated for intranasal administration” ([0150]). See also ([0152], [0260]).
Regarding instant claim 3, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 2 further comprising a second peptide and/or nucleic acid molecule encoding the second peptide and wherein the second peptide comprising at least a part of the S2 ectodomain of the S (spike) protein from at least one HCoV selected from HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1: “At least one antigenic coronavirus peptide selected from…a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof…” ([0008]); “The antigenic coronavirus peptide may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
The composition of claim 2 optionally also comprising a third peptide and/or a nucleic acid molecule encoding the third peptide and wherein the third peptide comprising at least a part of the S2 ectodomain of the S (spike) protein from at least one highly pathogenic human coronavirus selected from SARS-CoV-1, MERS-CoV and SARS-CoV-2 or from an animal coronavirus: “The fusion protein may comprise 2-10 antigenic coronavirus peptides connected in series…” ([0012]); “At least one antigenic coronavirus peptide selected from…a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof…” ([0008]); “The antigenic coronavirus peptide may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
Regarding instant claim 5, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
The composition of claim 2, wherein the peptide is conjugated to an immune stimulant: “The nanoparticle-forming peptide may comprise or be Helicobacter pylori ferritin (Hpf) or a fragment or variant thereof” ([0009]); “The nanoparticle may comprise one or more of an Hpf or a fragment or variant thereof connected via a peptide linker to…a stabilized extracellular spike domain (S-2P) or a fragment or variant thereof” ([0014]).
Regarding instant claim 6, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 2, wherein the peptide is in or attached to a nanoparticle: “The disclosed vaccine nanoparticles are made up of a plurality of fusion proteins that self-assemble into a nanoparticle…In the case of monomeric antigens such as the RBD, 24 coronavirus peptides can be presented on the surface of the self-assembling protein nanoparticle surface” ([0132]).
Regarding instant claim 7, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 2, wherein the nucleic acid molecule is comprised in a vector: “Bat SARSr-CoV S genes were cloned into a modified pcDNA3. l expression plasmid” ([0183]).
Regarding instant claim 8, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 2, comprising an adjuvant: “The vaccines may further comprise one or more adjuvants such as one or more selected from ALFQ, alhydrogel, and combinations thereof” ([0016]).
Regarding instant claim 10, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 2, wherein the composition increases immunity against at least two different coronaviruses: “In some embodiments, the disclosed vaccines may provide a broad-spectrum treatment and/or prevention for multiple different types of coronaviruses such as MERS-CoV, SARS-CoV and/or SARS-CoV-2” ([0107]); “The "beads on a string" concept can be used to create a nanoparticle with antigenic components from multiple coronaviruses such as SARS-CoV-2, SARS-CoV-1, HKU-1, MERSCoV, 229E, NL63, OC43, or related coronaviruses…these embodiments can be utilized to create a pan-β-coronavirus vaccine, or pan-coronavirus vaccine…beads comprised of different antigenic sequences can be provided together on a single “string” (i.e., in a single construct) to elicit broad immune responses against coronaviruses ([0141]).
Regarding instant claim 13, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
The method according to claim 11, wherein the human individual is not at risk for COVID-19 severe illness: “Any of the pharmaceutical compositions disclosed herein can be used for treating or preventing a coronavirus infection, such as SARS-CoV-2 infection (e.g., COVID-19)…” ([0154]); “In some embodiments, the administration of the vaccine prevents the subject from developing a coronavirus infection” ([0156]).
Regarding instant claim 14, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
The method according to claim 11, further comprising administering to the human individual a booster dose to maintain protective immunity: “In some embodiments, a subject may be administered an initial dose and then receive one or more booster doses with a predefined span of time in between each dose…” (0158]).
Regarding instant claim 15, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
The method according to claim 11, further comprising, subsequent to the administration, testing the immunity of said human individual against a pathogenic coronavirus: “Dosing regimens can be adjusted to provide the optimum desired response (e.g., production of antibodies and/or cytokines against a coronavirus such as SARS-CoV-2 or SARS-CoV-1 ([0158]); “Mouse sera was assayed for SARS-CoV-2 Spike-specific antibody response and the ratio of the isotypes, IgGa or IgGc, and IgG1-surrogates of TH1 and TH2 responses respectively” ([0251]).
Regarding instant claim 16, Joyce discloses the following embodiments of the coronavirus vaccine composition as a method to increase immunity:
It is unclear if the “at least one of the coronaviruses” is referring to the increased immunity in a human individual against at least two different coronaviruses or referring to the peptide from at least one human coronaviruses of instant claim 1 (see above claim rejection under 35 USC 112(b)).
If this limitation is referring to increased immunity: “In some embodiments, the disclosed vaccines may provide a broad-spectrum treatment and/or prevention for multiple different types of coronaviruses such as MERS-CoV, SARS-CoV and/or SARS-CoV-2” ([0107]); “The "beads on a string" concept can be used to create a nanoparticle with antigenic components from multiple coronaviruses such as SARS-CoV-2, SARS-CoV-1, HKU-1, MERSCoV, 229E, NL63, OC43, or related coronaviruses…these embodiments can be utilized to create a pan-β-coronavirus vaccine, or pan-coronavirus vaccine…beads comprised of different antigenic sequences can be provided together on a single “string” (i.e., in a single construct) to elicit broad immune responses against coronaviruses ([0141]).
If this limitation is referring to the peptide: “At least one antigenic coronavirus peptide selected from…a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof…” ([0008]); “The antigenic coronavirus peptide may be isolated or derived from a coronavirus selected from SARS-CoV-2, HCoV-OC32, MERS-CoV, SARS-CoV-1, HKU-1, 229E, or NL63 ([0013]).
Regarding instant claim 18, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 8, wherein the adjuvant is selected from a TLR3 or TLR4 agonist, murabutide, betaglycan, and/or cholera toxin: “Other vaccine adjuvants are known in the art, and based on the results reported herein with respect to ALFQ, and Alhydrogel, those of skill in the art will understand that other adjuvants also could be used with and complement the function of the disclosed nanoparticles. Other adjuvants that are suitable for use with the disclosed nanoparticles include, but are not limited to…Poly IC:LC, PolyI:C ([0148]).
Regarding instant claim 19, Joyce discloses the following embodiments of the coronavirus vaccine composition:
The composition of claim 10, wherein at least one of the at least two different coronaviruses is selected from SARS-CoV-1, MERS-CoV, and SARS-CoV-2: “In some embodiments, the disclosed vaccines may provide a broad-spectrum treatment and/or prevention for multiple different types of coronaviruses such as MERS-CoV, SARS-CoV and/or SARS-CoV-2” ([0107]); “The "beads on a string" concept can be used to create a nanoparticle with antigenic components from multiple coronaviruses such as SARS-CoV-2, SARS-CoV-1, HKU-1, MERSCoV, 229E, NL63, OC43, or related coronaviruses…these embodiments can be utilized to create a pan-β-coronavirus vaccine, or pan-coronavirus vaccine…beads comprised of different antigenic sequences can be provided together on a single “string” (i.e., in a single construct) to elicit broad immune responses against coronaviruses ([0141]).
Joyce teaches embodiments that correspond to the currently claimed limitations in instant claims 1, 3, 5-8, 10-16 and 18-19. As such, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the disclosed embodiments of Joyce to
arrive at the claimed invention. One of ordinary skill, armed with the disclosed embodiments of
Joyce, could easily arrive at the currently claimed invention with a predicted success because
Joyce teaches the disclosed compositions and methods as being successful in inoculating a
subject against coronavirus.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Joyce (previously cited in this Office Action) in further view of Crowe (US 2021/0300999 A1; published: 30 September 2021; effective filing date - finds full support in 63/000,299 filed on 26 March 2020).
The disclosures of Joyce are set forth above. While Joyce discloses a method and composition of a coronavirus vaccine to increase immunity, Joyce does not explicitly disclose the limitations of instant claim 17.
Crowe teaches antibodies binding to and neutralizing SARS-CoV-2 (abstract).
Regarding instant claim 17, Crowe discloses the following:
“As is well known in the art, a given composition for immunization may vary in its immunogenicity. It is often necessary therefore to boost the host immune system, as may be achieved by coupling a peptide or polypeptide immunogen to a carrier. Exemplary and preferred carriers are keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA). Other albumins such as ovalbumin…can also be used as carriers” ([0115]).
A combination of Joyce and Crowe disclose the limitations of instant claim 17. Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the combined teachings of the references to arrive at the claimed invention. Both Joyce and Crowe disclose methods of immunization against coronaviruses. While Joyce does not explicitly disclose using KLH conjugated to a peptide as an immunization strategy, Crowe discloses this technique is widely known in the art to boost host immune response to a peptide immunization. Therefore, one of ordinary skill would have predicted the prior art elements are capable of being combined and the combination would have worked for its intended purpose to increase immunity against a coronavirus.
Conclusion
Claims 1-19 are rejected. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A Rossi whose telephone number is (571) 272-0138. The examiner can normally be reached M-F 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIA A ROSSI/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
1 HCoV-NL63 UniProt Tool. https://www.uniprot.org/uniprotkb/A0A5B9BH95/feature-viewer.
2 Id.
3 Id.
4 Id.
5 HCoV-229E UniProt Tool. https://www.uniprot.org/uniprotkb/H1AG31/feature-viewer.
6 Id.
7 Id.
8 HCoV-OC43 UniProt Tool. https://www.uniprot.org/uniprotkb/P36334/feature-viewer.
9 Id.
10 Id.
11 Id.
12 Id.
13 HCoV-HKU1 UniProt Tool. https://www.uniprot.org/uniprotkb/U3NAI2/feature-viewer.
14 Id.
15 Id.
16 Id.
17 Id.