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 .
Disposition of Claims
Claims 1-8, 11, 14, 17-21, 23, 25, 27, and 32-33 are currently pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0357325 A1, Published 09 November 2023.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements filed on 12 March 2024 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. Foreign Patent Document WO 2016/166305 A1 was not considered as the document was split into two, so it was not submitted as one whole complete document. It has been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statements filed on 12 March 2024 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. No copies of Foreign Patent Documents WO 2022/008438 A1, JP 2023513544 A, WO 2021/159040 A2, KR 20220140586 A, CN115916815 A, WO 2022/029011 A1, EP 1944317 A2, WO 2021/207207 A3, WO 2014/123543 A2, WO 2022/214795 A1, KR 20220058090 A, or WO 2022271863 A1 were provided. While English equivalents for JP 2023513544 A, KR 20220140586 A, and CN115916815 A were identified, copies of the original Foreign Patent Documents themselves were not provided. They have been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statements (IDSes) submitted on 12 March 2024 have been considered by the examiner. Any individual references with strikethroughs, however, have not been considered, unless they have been cited on form PTO-892.
Drawings
The drawings are objected to because all or almost all parts of Figure 11 and Figure 23 are illegible. Also, in Figure 6B, the figure label is not placed by the ribbon that is supposed to be depicted in it. Additionally, the small text boxes beneath the color-coded domains in Figure 6B are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Drawings and Specification; Sequence Disclosure Requirements
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that The drawings and specification are objected to because Paragraphs 0012, 0098 (Figure 14 Legend), 0102 (Figure 18 Legend), 0247, and 0251, as well as Figure 27, all comprise sequences that do not identify said sequences with corresponding SEQ ID NOs within the figures themselves or within the figure legends of the specification. The sequences in question are MSFPQSAP in L1049MSFPQSAP1057 (Paragraph 0098); TYVTQQLIRAA in Q1005TYVTQQLIRAA1016 (Paragraph 0102); ILSRL in D979ILSRL984 (Paragraph 0102); VEAEVQIDRLITG in K986VEAEVQIDRLITG999 (Paragraph 0102); SSNFGAISSVLNDILSRLDKVEAEVQIDRLITGR (Figure 27 itself); RRAR (Paragraph 0247); KRSF (Paragraphs 0012 and 0247); and SNFGAISSV (Paragraph 0251). All of these sequences contain at least 4 specifically defined and enumerate amino acid residues and they therefore all require SEQ ID NOs. If these sequences correspond to existing SEQ ID NOs in the Sequence Listing, then they should be associated with their corresponding SEQ ID NO each and every time they appear throughout the disclosure. If they do not correspond to existing SEQ ID NOs in the Sequence Listing, then they should each be assigned their own unique SEQ ID NO. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The objection to the drawings will not be held in abeyance. Applicants must comply with sequence rules in order to be considered a complete response to this Office Action; a complete response would be to either submit corrected drawing sheets as noted below or to amend the specification to include the SEQ ID NOs within the figure legends.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. The hyperlink in question is www.interscience.wiley.com (Paragraph 0169). See MPEP § 608.01.
The disclosure is objected to because of the following informalities: In Paragraph 0025, it should say “…(SEQ ID NO: 4)” instead of “…(SEQ ID NO: 3)”.
In Paragraph 0039, it should say “…the subfamily Orthocoronavirinae, in the family Coronaviridae, in order Nidovirales…” instead of “…the subfamily Coronavirinae in the family Coronavirinae, in the order Noroviruses…”.
Paragraph 0208 ends with a sentence fragment. It states “As used herein, the term ‘engineered’ (as in an engineered cell) refers to a cell into which a nucleic acid molecule e.g., encoding a coronavirus S1/S2 prefusion spike peptide”. Please amend this paragraph so that it ends with a complete sentence.
In Paragraph 0250, it is suggested that it say “COVID-19 vaccines” instead of “CON/ID-19 vaccines”.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1-3, 7, and 17 are objected to because of the following informalities: In Claim 1, it is suggested that it say “…wherein the two or more amino acids are substituted…” instead of “…wherein the two amino acids are substituted…”.
In Claim 2, it is suggested that it say “…wherein the two amino acid[[s]] substitutions comprise cysteine” instead of “…wherein the two amino acids comprise cysteine”.
In Claim 3, it is suggested that it say “…prefusion spike peptide comprises a peptide having [[a]] 90% sequence identity to…” OR “…prefusion spike peptide comprises an amino acid sequence having [[a]] 90% sequence identity to…” instead of “…prefusion spike peptide comprises peptide having a 90% sequence identity to…”.
In Claim 7, it is suggested that it say “…comprises [[a]] cysteine substitutions at…” instead of “…comprises a cysteine substitution at…”.
In Claim 17, it is suggested that it say “…or an expression vector…” instead of “…or expression vector…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 1, and dependent claims 2-8, 11, 14, 21, 23, and 27 thereof, 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.
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 1 recites the broad recitation “two or more amino acid substitutions” in Line 2, and the claim also recites “wherein the two amino acids are substituted” also in Line 2, which is the narrower statement of the range/limitation. The claim is 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. It is suggested that the claim be amended by making both phrases use the same language, either “two or more amino acids” or “two amino acids”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claims 2-8, 11, 14, 21, 23, and 27 are also rejected, since they depend upon Claim 1 but do not remedy the deficiencies of Claim 1.
Claim 2 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.
Regarding Claim 2, it recites the limitation “The engineered peptide of claim 1, wherein the two amino acids comprise cysteine”. It is unclear which two amino acids are being referenced from claim 1, the original ones or the substitutions. It can reasonably be interpreted to refer to either pair of amino acids. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) (“[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.”) This lack of clarity renders the claim indefinite. It is suggested that the claim be amended to clarify which amino acids are being referenced, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 2 is rejected on the grounds of being indefinite.
Claims 3-7 and 18, and claims 8, 11, 14, 21, 23, and 27 thereof, 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.
Regarding Claim 3-7 and 18, they all utilize an amino acid numbering system which does not make sense in the context of the instant claim set. The numbering system used is based on, presumably, a full-length coronavirus spike protein. This is not recited in the claims, however. What is recited is SEQ ID NO: 1, which is only 34 amino acids long. As such, the numbering system should be based on the length of SEQ ID NO: 1, which is being used as the reference sequence in these claims. The presence of the source protein residue labels gives the claims two interpretations. First, residue 967 in the peptide of the claims must also be residue 967 in the prefusion spike peptide claimed. Second, 967 of the peptide need not be the same residue in the prefusion spike peptide, allowing for N-terminal tags, for example. The presence of multiple structural interpretations renders the claims indefinite. It is suggested that the numbering system be amended to align with SEQ ID NO: 1, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 3-7 and 18 are rejected on the grounds of being indefinite. Claims 5-7 and 8, 11, 14, 21, 23, and 27 are also rejected, since they depend upon Claims 4 and 3, respectively, but do not remedy the deficiencies of Claims 4 and 3.
Claims 32, and dependent claim 33 thereof, 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 32 is rejected for claiming the limitation of amino acid positions within a protein sequence without providing an appropriate frame of reference for said sequence. For instance, it is unclear if the amino acid positions are in reference to a full-length spike protein, a truncated spike protein, a tagged spike protein, etc. Said frame of reference can be provided by referencing a sequence disclosed within the application (i.e., a sequence with a SEQ ID NO: identifier) or by referencing a start position for said sequence (i.e., “…wherein said amino acid is at position X from the starting methionine of the protein…”), but Applicant is free to amend the claim as they deem necessary. Without some reference sequence, there are numerous structural interpretations of the positions.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 32 is rejected on the grounds of being indefinite. Claim 33 is also rejected, since it depends upon Claim 32 but does not remedy the deficiencies of Claim 32.
Claim 32 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.
Regarding Claim 32, it recites the limitation “A coronavirus S1/S2 prefusion spike protein comprising a disulfide bridge between a cysteine substituted for a phenylalanine (Phe) located between at least amino acid position 800 to about amino acid position 1100 and a cysteine substituted for a glycine (Gly) located 29 amino acids from the Phe amino acid, wherein the cysteines form a disulfide bridge.” The wording of the claim is particularly awkward and muddles the presumed intention of the claim language. While it is assumed that Applicant’s intention was to recite that the cysteines are replacing the original amino acids, the claim, as written, can be reasonably interpreted as having the opposite meaning. The phrase “a cysteine substituted for a phenylalanine” can be interpreted as meaning that the phenylalanine is replacing the cysteine. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) (“[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.”) This lack of clarity renders the claim indefinite. It is suggested that the claim be amended to make Applicant’s intentions clear. One suggestion is to mirror the language used in dependent Claim 33, which makes it clear which amino acid is being replaced, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 32 is rejected on the grounds of being indefinite.
Claims 32, and dependent claim 33 thereof, 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.
Regarding Claim 32, it recites the limitation “A coronavirus S1/S2 prefusion spike protein comprising a disulfide bridge between a cysteine substituted for a phenylalanine (Phe) located between at least amino acid position 800 to about amino acid position 1100 and a cysteine substituted for a glycine (Gly) located 29 amino acids from the Phe amino acid, wherein the cysteines form a disulfide bridge.” The use of the term “about” renders this claim indefinite as there is no clear definition provided in the instant Specification. Paragraph 0031 attempts to define it by stating that “The term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, "about" can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value or range. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, and also within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term "about" meaning within an acceptable error range for the particular value should be assumed. All numeric values are herein assumed to be modified by the term "about", whether or not explicitly indicated. The recitation of numerical ranges by endpoints includes all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).” Given the lack of a clear definition in the instant Specification, it is unclear how “about” should be interpreted in the context of the claim. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended by removing the word “about”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 32 is rejected on the grounds of being indefinite. Claim 33 is also rejected, since it depends upon Claim 32 but does not remedy the deficiencies of Claim 32.
Claim Interpretation
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 Rejections - 35 USC § 112(a); First Paragraph
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 3, 8, 11, 14, 21, 23, and 27 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 coronavirus S1/S2 prefusion spike peptide comprising an amino acid sequence which is 100% identical to instant SEQ ID NO: 1, does not reasonably provide enablement for variants of the coronavirus S1/S2 prefusion spike peptide comprising amino acid sequences with less than 100% sequence identity to instant SEQ ID NO: 1. 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.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to an engineered peptide comprising a coronavirus S 1/S2 prefusion spike peptide sequence having two or more amino acid substitutions, wherein the two amino acids are substituted at conserved amino acid positions of the coronavirus S1/S2 prefusion spike peptide sequence, wherein the coronavirus S1/S2 prefusion spike peptide comprises peptide having a 90% sequence identity to S967SNF970GAISSVLNDILSRLDKVEAEVQIDRLITG999R1000 (SEQ ID NO: 1).
State of the prior art/Predictability of the art. The art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. For example, replacement of a single “lysine” residue at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess et al., J of Cell Bio. 111:2129-2138, 1990). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (Proceedings of the National Academy of Sciences, U.S.A., Vol. 88, Pg. 2658-2662, 1991) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (Immunity, Vol. 13, Pg. 475-484, 2000) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In another case, Huang (The Journal of Biological Chemistry, Vol. 272, No. 43, Pg. 27155-27159, 1997) teaches that conjugation of peptides to other proteins can change their biological properties. They teach that multiple conjugation of the peptide TGFβ1 (residues 41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as well (Abstract). Thus, the chemical context of a biologically active peptide is also important.
Truncation of proteins can also lead to adverse effects on protein structure and thus protein function. Martindale (Nature Genetics, Vol. 18, Pg. 150-154, 1998) teaches that truncation of huntingtin leads to aggregate development which compromises cell viability (Abstract). Nonaka (Human Molecular Genetics, Vol. 18, No. 18, Pg. 3353-3364, 2009) teaches that truncation of TDP-43 to its C-terminal fragments causes abnormally phosphorylated and ubiquitinated inclusions of the protein (Abstract). Taken together, not just any truncation of a protein will yield a soluble, functional, protein fragment.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through conjugation or mutagenesis. Importantly, binding can still occur after mutation or conjugation in the literature examples provided above, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (The Journal of Biological Chemistry, Vol. 272, Pg. 21201-21206, 1997) who teaches that receptor binding does not predict agonist or antagonist activity (Pg. 21205, Column 2, Paragraph, first full, Sentence, first).
Working examples. No working examples of the claimed variants are disclosed in the specification.
Guidance in the specification. The specification provides guidance towards constructs which presumably comprise sequences which have 100% sequence identity to instant Claim 1. The instant Specification, however, fails to disclose the critical or essential amino acids which must be present and any variants of the claimed sequence. While it does include information on conservative amino acid substitutions and variants of polypeptides, it also notes that these variants may comprise nonconservative changes, as well as deletions, insertions, or both (see Paragraphs 0043 and 0078).
Amount of experimentation necessary. Since the art teaches that it is unpredictable whether or not peptide variants of known inhibitors will function as such and it is also unpredictable that even a known inhibitory peptide that functions in vitro will function in vivo, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the products of instant claims as broadly as they are currently claimed.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed product.
Claims 8 and 17-20 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 an immunogenic composition comprising the claimed engineered peptide and a method of treating a subject infection with a coronavirus, does not reasonably provide enablement for a vaccine comprising the claimed engineered peptide or a method of preventing infection. 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.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to an engineered peptide comprising a coronavirus S 1/S2 prefusion spike peptide sequence having two or more amino acid substitutions, wherein the two amino acids are substituted at conserved amino acid positions of the coronavirus S1/S2 prefusion spike peptide sequence, a vaccine comprising said engineered peptide, and a method of preventing infection and treating a subject infected with a coronavirus, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a coronavirus S1/S2 prefusion spike peptide or expression vector encoding the coronavirus S1/S2 prefusion spike peptide. The term “coronavirus” is defined in the instant Specification as encompassing “all strains, genotypes, protectotypes, and serotypes of this virus”, belonging to “the subfamily Coronavirinae in the family Coronavirinae, in the order Noroviruses” (see Paragraph 0039). The term “vaccine” is defined in the instant Specification as “a pharmaceutical composition that elicits a prophylactic or therapeutic immune response in a subject”, where, in some cases, “the immune response is a protective immune response” and that, typically, “vaccines elicit antigen-specific immune responses against pathogens, such as antigens of viral pathogens or cellular components associated with pathological conditions” (see Paragraph 0076). The term “treating” is defined to “include administering a compound or agent to a subject to prevent or delay the onset of symptoms, complications or biochemical indicators of a disease (e.g., a coronavirus infection), alleviate symptoms or arrest or inhibit further development of the disease, condition or disorder” (see Paragraph 0073). This paragraph also states that treatment “may be prophylactic (to prevent or delay the onset of the disease, or to prevent the manifestation of clinical or subclinical symptoms thereof) or may be therapeutic inhibition or symptomatic relief following the manifestation of the disease”.
State of the prior art/Predictability of the art. Reasonable guidance with respect to preventing any viral infection relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of viruses. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical infection and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease. Therefore, Applicant may provide data showing prevention in vivo.
As stated in Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985): [B]ased upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence. (Citations omitted.) Therefore, in the absence of the in vivo data above, Applicant may also provide evidence of pharmacological activity that would reasonably correlate with prevention of infection.
In the case of virus vaccines, a reasonable nexus exists between neutralizing antibody generation and prevention of infection. Thus, a showing that an antigen within the recited immunogen scope can produce such antibodies would support enablement for use of said antigen in a vaccine and/or methods of preventing infection therewith of the virus comprising said antigen.
Burton (Nature Reviews Immunology, Vol. 2, Pg. 706-713, 2002) teaches neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases (Abstract). Figure 1 divides antiviral activities of antibodies into two groups: activities against free virus and activities against infected cells. Actual block of infection (prevention of infection) is taught to be the role of neutralizing antibodies (Figure 1). Nonneutralizing antibodies thus cannot prevent infection, only treat an infection.
Adding to the unpredictability is the fact that not just any epitope of a target antigen/virus will lead to antibody generation, let alone that of neutralizing antibodies. Riddell (Journal of Virology, Vol. 74, No. 17, Pg. 8011-8017, 2000) at the abstract teaches patient sera reacts with some but not all B-cell epitopes on ORF7.1 protein. Thus, not just any epitope/antigen/immunogen will contribute to patient immunity against a virus. Sugiyama (Journal of Virology, Vol. 76, No. 4, Pg. 1691-1696, 2002) supports this by teaching in their abstract that even amongst known epitopes that lead to neutralizing antibodies in some species, another subject’s immune reaction will not necessarily generate antibodies against all said epitopes.
Burton (PNAS, Vol. 108, No. 27, Pg. 11181-11186, 2011) teaches three anti-HIV antibodies. Antibodies b12 and b6 bind CD4 binding sites while F240 binds gp41 (Abstract). All were tested for prevention of SHIV transmission to macaques (Abstract). While the two anti-gp120 antibodies have similar binding properties, b12 is strongly neutralizing and b6 is not (Abstract). F240 is nonneutralizing (Abstract). Compared to controls, the protection by b12 achieved statistical significance while no such protection was seen for either b6 or F240 (Abstract). Thus, the work of Burton supports the conclusion that neutralizing antibodies are required for prevention and so a functional vaccine should produce such. It also supports the idea that not just any peptide on protein may generate neutralizing antibodies that protect as evidenced by b12 and b6 performance above. Data are clearly required to calm the concerns of the prior art and make methods of viral infection prevention and vaccine products predictable.
Taken together, it is clear from the prior art that a PHOSITA cannot predict the preventative power of any immunogen. They must be shown data that supports such a conclusion. Without demonstration of neutralizing antibody production, for example, in the target population with the specific immunogen, no practitioner in this art would see any given immunogen as a functional, predictable prophylactic agent.
Working examples. No working example is disclosed in the specification. Any examples present in the instant Specification are prophetic or hypothetical in nature.
Guidance in the specification. The specification provides guidance towards structural modeling of the designed constructs. Paragraph 0285 states that data “generated based on the model herein demonstrate that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection” and that prefusion “S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity”. No actual human data is provided, however. In fact, no in vitro or in vivo data is provided using the claimed engineered peptide.
Amount of experimentation necessary. Additional research is required in order to determine how effective the claimed engineered peptide would be at preventing infection with a coronavirus and acting as part of a vaccine.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed products and/or methods.
Claims 11 and 14 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 an isolated expression vector, an isolated nucleic acid molecule, or an isolated host cell comprising said vector or nucleic acid molecule, does not reasonably provide enablement for a cell within a transgenic animal or a transgene therein. 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.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are broadly drawn to an expression vector or nucleic acid molecule comprising a nucleotide sequence encoding the claimed engineered peptide or a host cell comprising said vector or nucleic acid molecule. The claims read on a cell within a transgenic animal or a transgene therein given that the term “isolated” is not denoted in describing the vector, nucleic acid molecule, or host cell.
State of the prior art/Predictability of the art. With respect to the unisolated host cells and transgenes as “nucleic acids” or “vectors “of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second).
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use functional polynucleotides that produce the engineered peptide thereof, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed engineered peptide is functional, commensurate in scope with the claimed invention. The same can be said for the transgenes and transgenic animals encompassed by the instant claims. Thus, the claims are rejected here.
Working examples. No working example of a transgenic animal is disclosed in the specification. The working examples disclosed in the Specification describe the expression vector and cells used to express the engineered peptide, in generic terms, such as viral vectors like adenovirus and prokaryotic and eukaryotic cells (see Paragraphs 0165-0168, 0208).
Guidance in the specification. The specification provides guidance towards viral vectors as a potential delivery system for the claimed engineered peptide. The specification also provides guidance towards the engineered peptide of the invention being expressed in fungal cells, yeast cells, bacterial cells, avian cell, or mammalian cells (see Paragraphs 0165-0168, 0208).
Amount of experimentation necessary. At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "host cell" and by amending the vector and nucleic acid molecule claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the engineered peptide encoded by the claimed expression vector or nucleic acid molecule.
Claims 3, 8, 11, 14, 21, 23, and 27 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 instant application attempt to tie function to sequence identity in the context of an engineered peptide comprising a coronavirus S 1/S2 prefusion spike peptide sequence having two or more amino acid substitutions, wherein the two amino acids are substituted at conserved amino acid positions of the coronavirus S1/S2 prefusion spike peptide sequence, wherein the coronavirus S1/S2 prefusion spike peptide comprises peptide having a 90% sequence identity to S967SNF970GAISSVLNDILSRLDKVEAEVQIDRLITG999R1000 (SEQ ID NO: 1). While a percent identity threshold is provided in the claims, the instant Specification fails to disclose the critical or essential amino acids which must be present and that therefore cannot be changed and any variants of the claimed sequence. While it does include information on conservative amino acid substitutions and variants of polypeptides, it also notes that these variants may comprise nonconservative changes, as well as deletions, insertions, or both (see Paragraphs 0043 and 0078). The claim language does not limit how the claimed changes can be interpreted. As such, the claims read on variants of the claimed sequences with nonconservative substitutions, deletions, and/or insertions. As such, it would be unclear to a person having ordinary skill in the art to know what to change and what not to change.
Furthermore, while it is not explicitly stated, it is assumed that the constructs used in the instant Specification have sequences which are 100% identical to the claimed sequence. Even if that is not the case, the data shown do not explicitly include any claimed variants having as little as 90% sequence identity, or even 91-99% sequence identity, raising questions about how effective these claimed variants would be in the data provided. Thus, it is not clear what was tested, it does not appear that any claimed variants were tested, and the essential characteristics of the genus being claimed by Applicant have not been identified or disclosed. One way to overcome the instant Written Description rejection is for Applicant to show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that Applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.
“[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.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
MPEP § 2163 states that 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, 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the peptide variants can have any sequence which varies from instant SEQ ID NO: 1 by as much as 10%, one must describe a sufficient variety of species to reflect the variation within the genus. However, one of skill in this art cannot envision the structure of any other peptide variants with the required sequence identity other than the few species provided by Applicant and the prior art. Therefore, since only a few species are provided to represent the genus, the claims encompassing the same clearly fail the written description requirement.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Overall, at the time the invention was made, the level of skill for preparing peptide variants and then selecting those peptides which meet the desired percent identity cutoff was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptide variants with the recited percent identity cutoff, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010). Absent the conserved structure provided by a core peptide sequence, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what any peptide which meets the recited percent identity cutoff would look like structurally.
While applicant has described a few species within the genus recited, and the art may provide more, each genus is very large and would encompass peptide structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the peptide structures encompassed by the claimed/recited genus only defined by sequence identity. Any future peptide variant may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the entire recited genus of peptide variants. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As such, it does not appear Applicant was in possession of the full scope of the claimed invention at the time of filing and thus Claims 3, 8, 11, 14, 21, 23, and 27 do not meet the written description requirement.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 14 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). In Paragraph 0208 of the instant Specification, human cells are specifically contemplated. It is suggested that the claim be amended to recite “An isolated host cell”, but Applicant is free to amend the claim as they deem necessary.
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.
(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 1-8, 11, 14, 17-21, 23, 25, 27, and 32-33 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Oostvogels et al. (US 2022/0211838 A1, earliest Priority Date 29 May 2020).
Oostvogels et al. teach at least one antigenic peptide or protein from a coronavirus Spike protein (see Abstract), wherein said spike protein comprises the S1 fragment and at least part of the S2 fragment (see Paragraphs 0105-0109) or a full-length spike protein (see Paragraph 0110) and is stabilized in a prefusion conformation as a result of one or more amino acid substitutions, deletions, or insertions which can introduce intramolecular disulfide bonds (see Paragraph 0111-0119), which reads on instant Claim 1. Oostvogels et al. teach SEQ ID NO: 1, which is an amino acid sequence that comprises a sequence that has 100% sequence identity to instant SEQ ID NO: 1 (see Sequence Listing; Paragraphs 0259-0262; see attached Sequence Alignment**), which reads on instant Claims 3-4. Oostvogels also teach SEQ ID NO: 3422, which is an amino acid sequence that comprises a sequence having at least 90% sequence identity to instant SEQ ID NO: 1 (see Sequence Listing). Prior art sequence SEQ ID NO: 3422 comprises cysteine substitutions at positions 4 (Phe) and 33 (Gly), which serve to form an artificial intramolecular bond (see Paragraphs 0259-0260), corresponding to positions 970 and 999 according to Applicant’s numbering system, which reads on instant Claims 2-3, 5-7, and 32-33.
Oostvogels et al. also teach the at least one antigenic peptide or protein being encoded by a nucleic acid, expressed by a vector, comprised within a vaccine, and conjugated to a secondary agent, such as another antigenic peptide or protein or a lipid nanoparticle (LNP), as well as its use in a pharmaceutical composition in a method for preventing infection and treatment of an infection with at least one coronavirus comprising administering an expression vector encoding the at least one antigenic peptide or protein (see Abstract; Paragraphs 0003, 0076, 0122, 0278, 0554, 0623, 1060-1061, 1063-1064, 1373-1377, 1497-1502), which reads on instant Claims 8, 11, 17-18, and 21.
Additionally, Oostvogels et al. teach mammalian host cells transfected with the nucleic acid encoding the at least one antigenic peptide or protein (see Paragraphs 0984-0985), which reads on instant Claim 14, as well as compositions comprising a plurality or at least more than one of the nucleic acid species comprising at least one coding sequence encoding at least one antigenic peptide or protein, wherein all the proteins or peptides have the same amino acid sequence (see Paragraph 0416), which reads on instant Claim 23, wherein the multiple antigenic peptides or proteins are connected via an amino acid linker (see Paragraph 1029), which reads on instant Claim 25.
Furthermore, Oostvogels et al. teach pharmaceutical compositions comprising a nucleic acid encoding the at least one antigenic peptide or protein, wherein the nucleic acids further encode immunologic adjuvant sequences (see Paragraphs 0122, 0278, 0554, 0623, 1373-1377), which reads on instant Claim 27.
Finally, Oostvogels et al. teach a method comprising administering said pharmaceutical compositions, wherein said method further comprises administering to a subject a vaccine, such as a booster dose after a priming dose in a prime-boost regimen (see Paragraphs 1517, 1553-1554), or an agent, such as another antigenic peptide or protein, another antigen-encoding nucleic acid, a further immunotherapeutic agent, and/or an adjuvant nucleic acid, such as an immunostimulatory RNA (isRNA) (see Paragraphs 1377), which reads on instant Claims 19-20.
For at least these reasons, Oostvogels et al. teach the limitations of instant Claims 1-8, 11, 14, 17-21, 23, 25, 27, and 32-33 and anticipate the invention encompassed by said claims.
Claims 1, 3-4, 8, 11, 14, 17-21, 23, 25, and 27 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Georges and Roberts (US 2021/0260180 A1, Published 26 August 2021).
Georges and Roberts teach an adenoviral vector or expression cassette comprising a coding sequence encoding at least one coronavirus antigen comprising at least the S1 and/or S2 domains of a coronavirus spike protein which has been stabilized in its prefusion conformation via stabilizing mutations, or immunogenic fragments thereof (see Paragraphs 0122-0123, 0175), as well as SEQ ID NO: 367, which is 100% identical to instant SEQ ID NO: 1 (see Sequence Listing), which reads on instant Claims 1, 3-4, and 11.
Georges and Roberts also teach an immunogenic composition or a vaccine comprising said coding sequence encoding at least one coronavirus antigen (see Paragraph 0120, 0126-0127), which reads on instant Claim 8, as well as host cells comprising the expression vector, which reads on instant Claim 14.
Additionally, Georges and Roberts teach wherein the vector can further comprise multiple epitopes as part of a single polypeptide with each epitope separated by an amino acid linker (see Paragraphs 0183-0187), and wherein the vector can further comprise at least one polynucleotide encoding a polypeptide and/or peptide corresponding to a molecular adjuvant (see Paragraphs 0206-0207, 0248, 0283), which reads on instant Claims 21, 23, 25, and 27.
Furthermore, Georges and Roberts teach methods for treating and/or preventing COVID-19 comprising administering the immunogenic composition adenoviral vector or expression cassette comprising a coding sequence encoding at least one coronavirus antigen comprising at least the S1 and/or S2 domains of a coronavirus spike protein which has been stabilized in its prefusion conformation (see Paragraphs 0009-0010, 0015-0016), which reads on instant Claims 17-18. Finally, Georges and Roberts teach methods further comprising administering to the subject an agent, wherein said agent is an anti-cytokine reagent (see Paragraph 0244), which reads on instant Claims 19-20.
For at least these reasons, Georges and Roberts teach the limitations of instant Claims 1, 3-4, 8, 11, 14, 17-21, 23, 25, and 27 and anticipate the invention encompassed by said claims.
Conclusion
No Claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Erickson and Silva (U.S. Patent No. 7,151,163 B2, Issued 19 December 2006)
Erickson and Silva teach SEQ ID NO: 183, which comprises a sequence that is 100% identical to instant SEQ ID NO: 1. This reference has not been utilized, as rejection would have been redundant to those set for above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671