DETAILED ACTION
Election/Restrictions
Applicant’s election of species filed August 1, 2025 is acknowledged. The elected species are: protein/peptide, envelope, Dengue, and SEQ ID NO: 1. Claims 52, 55, 56, 67, 69 and 70 is withdrawn from consideration being directed to a nucleic acid embodiment.
Drawings
The drawings are objected to because Figure 14B contains amino acid sequences that need sequence identifiers.
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.
In lieu of filing corrected drawings, Applicant may amend the description of Figure 14B in the specification to recite the sequence identifiers.
Specification
The disclosure is objected to because of the following informalities: Paragraph [0066] contains an amino acid sequence that needs a sequence identifier. Appropriate correction is required.
The use of the terms Adjumer, Montanide, TiterMax, etc. (see paragraphs [0048]-[0049], [0051], [0052], [0053], and possibly others in the specification) which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claims Summary
Claim 1 is directed to a composition comprising a protein or peptide, or variant, homologue, derivative or subsequence thereof, that comprises, consists or consists essentially of a flavivirus B cell epitope, and the same for a flavivirus T cell epitope. The composition elicits, stimulates, induces, promotes, increases or enhances an antibody response and T cell response against two or (and (claim 2)) more different serotypes or species of flavivirus. The protein, etc. is a flavivirus envelope (claim 3). The protein, etc. is from Dengue serotypes 1-4 (claim 9). The protein, etc. comprises, consists or consists essentially of a consensus amino acid sequence derived from proteins or peptides from two or more different serotypes or species of flavivirus (claim 15). The composition further comprises a CD70 protein, etc. (claim 22). Also claimed is a method of eliciting, etc., an immune response against a flavivirus by administering the composition (claim 28), resulting in an immune response against two or more different serotypes or species of flavivirus (claim 29).
Claim 37 is directed to a composition comprising at least one polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO: 1, and a pharmaceutically acceptable buffer or excipient. SEQ ID NO: 1 represents a DENV1 E protein with fusion loop mutations (see Table 2 of the specification). Claim 38 is directed to an embodiment comprising two such polypeptides. The composition further comprises an effective amount of an adjuvant (claim 49), CD70 (claim 51). Also claimed is a method of eliciting an immune response against a flavivirus in a subject by administering an effective amount of the composition (claim 107), wherein the flavivirus is a dengue virus (claim 108).
Claim Objections
Claims 9, 37, 38, 49, 51, 107 and 108 are objected to because of the following informalities:
Claim 9 recites, “comprising proteins or peptides”…“from DENV1-4”. It appears that Applicant intends that the proteins or peptides be selected from serotypes 1-4. The current claim language appears to indicate that proteins or peptides from all four serotypes are present. Clarification with the use of “or” or “selected from the group consisting of”, or equivalent language is required.
Claim 37 recites (a), (b) and (e), without (c) and (d). Claims 38, 49, and 51 are included in this objection because they depend from claim 37.
Claim 107, line 3, recites “claims 37” [emphasis added], which should be “claim 37”. Claim 108 is included in this objection because it depends from claim 107. Further, claim 108 recites “wherein the flavivirus comprises a dengue virus”. More appropriate language would be “wherein the flavivirus is a dengue virus” in the context of claim 107’s method of eliciting an immune response against a flavivirus. Appropriate correction is required.
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 1-3, 9, 37 and 38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. Claims 1-3 and 9 are directed to a composition comprising a protein or peptide or subsequence thereof that comprises, consists or consists essentially of a flavivirus B cell epitope, and a protein or peptide or subsequence thereof that comprises, consists or consists essentially of a flavivirus T cell epitope, wherein the composition elicits, stimulates, induces, promotes, increases or enhances an antibody response and T cell response against two or more different serotypes and/or species of flavivirus. The protein, peptide or subsequence thereof is from an envelope protein from DENV 1-4. The judicial exception in claims 1-3 and 9 is a product of nature, specifically, a flavivirus envelope protein, a peptide or subsequence thereof. The claimed protein, peptide and subsequence are not markedly different from the products’ naturally occurring counterparts in their natural state because they are not modified relative to the original protein, peptide and subsequence. Although a function is associated with the protein, peptide and subsequence, regarding immunogenicity, there remains no alteration recited in the claims that makes it distinct from its naturally occurring counterpart.
Claims 37 and 38 are directed to a composition comprising a pharmaceutically acceptable buffer or excipient and at least one or at least two polypeptides having an amino acid sequence at least 90% identical to SEQ ID NO: 1, which is a sequence from DENV 1. The judicial exceptions in claims 37 and 38 are products of nature, specifically, a pharmaceutically acceptable buffer or excipient, which reads on water, and a DENV1 polypeptide sequence. The water, for example, is not markedly different from naturally occurring water. Likewise, the polypeptide sequence that is at least 90% identical to SEQ ID NO: 1 (a DENV1 polypeptide sequence) is not markedly different from its naturally occurring counterpart. WO2012/082073A1 discloses a sequence of a clinical isolate DENV1 strain, WestPac 74 (see page 36, first full sentence, and Figure 9ii). The sequence is 97.4% identical to Applicant’s SEQ ID NO: 1. Thus, the natural product’s sequence meets the criteria for at least 90% sequence identity to SEQ ID NO: 1. An alignment is provided at the end of this rejection.
These judicial exceptions are not integrated into a practical applications because placing the products of nature into “compositions” does not add a meaningful limitation because they are merely a nominal component of the claims. As seen in WO2011/146933 A2, compositions and water, as a pharmaceutical vehicle, are common in the art of Dengue virus proteins (see page 3, lines 7-9, and page 13, lines 16-20).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Therefore, the claims are directed to product of nature judicial exceptions and are not patent eligible.
Alignment of Applicant’s SEQ ID NO: 1 (“Qy”) with clinical isolate DENV1 strain, WestPac 74 (see WO2012/082073A1, page 36, first full sentence, and Figure 9ii)
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Claim Rejections - 35 USC § 112
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 1-3, 9, 15, 22, 28 and 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims are directed to variants, homologues, derivatives and subsequences thereof, of B cell epitopes, T cell epitopes and CD70. The content of these structures is not clearly set forth in the claims or the specification. The specification does not appear to offer any definition of a variant, homologue, derivative, and thus any subsequence thereof. The structure that is retained from the original protein/peptide is not provided. Without such, one would not know the structure of these variants, homologues, derivatives, and thus their subsequences. The metes and bounds of the claims cannot be determined.
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 1-3, 9, 15, 28, 37, 38, 49, 107 and 108 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ross et al. (WO 2011/146933 A2, “Ross”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Ross discloses compositions comprising dengue virus E proteins and fragments thereof from serotypes 1-4 that include B and T cell epitopes (claims 1-3 and 9), as well as consensus sequences (claim 15), and methods of immunization against single or multiple serotypes (see pages 2-3 in total, and page 26, lines 15-21) (claims 28, 29, 107 and 108). Ross discloses the use of adjuvants (page 32, lines 8-20) (claim 49). Ross’ SEQ ID NO: 2 is 98.3% identical to Applicant’s SEQ ID NO: 1 (claim 37), representing an E polypeptide. An alignment is provided below. Applicant’s SEQ ID NO: 1 is “Qy”, and Ross’ SEQ ID NO: 2 is “Db”. Ross also discloses VLPs (see page 3, lines 8-10) which comprise more than one E polypeptide (claim 38). Therefore, the claims are anticipated by the prior art.
Alignment of Applicant’s SEQ ID NO: 1 “Qy” with Ross’ SEQ ID NO: 2 “Db”
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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.
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 22 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Ross et al. (WO 2011/146933 A2, “Ross”) as applied to claims 1 and 49 above, and further in view of Shirwan et al. (US 8,017,582 B2, “Shirwan”). The claims are directed to an embodiment wherein the composition further comprises a CD70 protein.
The teachings of Ross are summarized above. While Ross discloses the use of adjuvants, such as costimulatory molecules and biological adjuvants, no particular suggestion to administer CD70 is provided (see Ross, page 32, lines 8-20). However, it would have been obvious to have administered any costimulatory molecule with a reasonable expectation of success. Shirwan discloses CD70 as a costimulatory molecule to be administered in conjunction with an antigen associated with an infectious agent such as a flavivirus (see col. 11, lines 29-44 and Table 6). One would have been motivated to improve the immunogenicity of the polypeptide by administering a costimulatory molecule, as taught by Shirwan. Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1671
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