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 .
DETAILED ACTION
Priority
This application is a continuation of U.S. Application No. 15/573,701, filed on November 13, 2017, now abandoned; and a continuation-in-part of national stage application PCT/ US2016/032317, filed May 13, 2016, which claims priority to U.S. Provisional Application No. 62/241,599, filed October 14, 2015, which claims priority to U.S. Provisional Application No 62/161,123, filed May 13, 2015 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 07/13/2023 is acknowledged. Claims 1-47 are pending and under examination.
Information Disclosure Statement
There was no information disclosure statement (IDS) submitted at the time of this office action.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 61). 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:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Drawings Objections
The drawings are objected to because Figures 23-25 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.
Claim Objections
Claims 1, 8, 15,16, 20, 26, 37 and 42-44 are objected to for the following informalities:
Claim 1 should recite “conserved element (CE)” prior to reciting “CE” for clarity.
Claim 16 should have a period at the end of the sentence.
Claims 8, 15, 20, 26 and 37 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1 and 42-44 recite polypeptides with no sequence identifier, for example, “nucleic acid sequence encoding p24GagCE1” and “P24CE8-1”. The claims are required to include a sequence identification number (SEQ ID NO.) for each polypeptide. MPEP 1.821 states “(d) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing" in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application”. Appropriate corrections are required.
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.
Claims 1, 30, 40 and 42-46 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1 and 42-46 are rejected for containing a reference to tables and figures. MPEP 2173.05(s) states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim' . Dependent claims 45 and 46 are rejected as being dependent upon claims 42 and 43, respectively.
Claims 1, 30 and 40 recite “substantially”. The term “substantially” is not clear in that it is a relative term. Further, the specification does not define the term “substantially” and does not provide a standard for ascertaining the requisite degree, thus a skilled artisan would not be apprised to the metes and bounds of the recitations. Thus, the claims are rendered indefinite.
Claim 43 recites “of claim 82 or 83”. There is no claim 82 or 83. There is insufficient antecedent basis for this limitation in the claim. Accordingly, one of ordinary skill in the art would not know the metes and bounds of the claims.
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.
Claim 41 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pavlakis et al. “Pavlakis” (WO2013/131099).
The claims are directed to an HIV Gag CE polypeptide comprising: (a) SEQ ID NO: 27, 29, 31, 33, 35 and/or 37; or (b) SEQ ID NO: 28, 30, 32, 34, 36, and/or 38.
Regarding claim 41, Pavlakis discloses methods and compositions for eliciting immune responses by altering the immunodominance hierarchy of HIV GAG by expressing highly conserved elements from a virus (Abstract). Pavlakis discloses SEQ ID NO: 27 (SEQ ID NO: 2, claim 3 of Pavlakis).
Therefore, the cited prior art anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-3 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al. “Pavlakis” (WO2013/131099).
The claims are directed to a method of inducing an immune response to HIV Gag in a subject, the method comprising: priming an immune response to HIV Gag, wherein priming comprises administering fo the subject a CE-encoding expression vector that comprises a nucleic acid sequence encoding p24GagCE1 as set forth in Table 2 fused at the N- terminus to a human GM-CSF signal peptide and a nucleic acid sequence encoding p24GagCE2 as set forth in Table 2 fused at the N-terminus to a human GM-CSF signal peptide, wherein the subject is not co-administered or has not previously been administered a recombinant nucleic acid construct encoding a full-length or substantially full-length HIV Gag polypeptide; and boosting an immune response to HIV Gag, wherein boosting comprises co-delivering the CE-encoding expression vector with an expression vector that encodes full-length HIV-1 p55gag or substantially full-length HIV-1 p55gag.
Regarding claim 1, Pavlakis discloses methods and compositions for eliciting immune responses by altering the immunodominance hierarchy of HIV GAG by expressing highly conserved elements from a virus (Abstract). Pavlakis teaches a method of HIV vaccination comprising administration of priming step comprising a nucleic acid encoding a first conserved element polypeptide that comprises at least 7 conserved elements from HIV-1 p24gag concurrent with administration of a nucleic acid construct encoding a second conserved element that comprises at least one variant of a conserved element differing by 1-3 amino acid (paragraphs [0007]-[0014]). Pavlakis further teaches boosting with the nucleic acid encoding the full-length protein concurrent with the conserved elements (paragraph [0066] and [0067]).
Pavlakis does not teach that the boosting composition may comprise the full-length protein (e.g. p24gag) or nucleic acid encoding same in combination with the priming composition.
However, one of ordinary skill in the art would have considered it obvious to do so in view of the teaching of Pavlakis. Pavlakis teaches that the priming step may comprise concurrent delivery of the priming composition along with the full-length protein or nucleic acid encoding same, and further teaches throughout that priming step and boosting steps may comprise delivery of “one or more” such steps. It is prima facie obvious to rearrange the sequence of adding ingredients. See M.P.E.P. § 2144.04(IV). It is also prima facie obvious to engage in rearrangement of parts, which is analogous to the present situation, where the instant invention constitutes a rearrangement of parts (i.e. priming compositions and boosting compositions) within the context of the steps disclosed by Pavlakis. See M.P.E.P. § 2144.04(VI). Finally, one of ordinary skill in the art would have considered the invention to be reached through routine experimentation or optimization within the prior art conditions set forth in Pavlakis, since Pavlakis teaches a priming step identical to the instantly recited priming step, and a boosting step that differs from the instantly recited boosting step only in that it is supplemented with a further administration of the priming composition. Furthermore, since all such compositions and steps are disclosed in the teachings of Pavlakis, one of ordinary skill in the art would have had a reasonable expectation of success in the absence of evidence to the contrary. Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 2, Pavlakis discloses the boost is administered from two weeks to four months following administration of the initial vaccine (paragraph [0067]).
Regarding claim 3, Pavlakis discloses two priming steps separated by two months and a boost step separated by another two months (Figure 20). With respect to a second boost step two months after the first boost step, Pavlakis teaches throughout that priming step and boosting steps may comprise delivery of “one or more” such steps. It is prima facie obvious to rearrange the sequence of adding ingredients. See M.P.E.P. § 2144.04(IV). It is also prima facie obvious to engage in rearrangement of parts, which is analogous to the present situation, where the instant invention constitutes a rearrangement of parts (i.e. priming compositions and boosting compositions) within the context of the steps disclosed by Pavlakis. See M.P.E.P. § 2144.04(VI). Finally, one of ordinary skill in the art would have considered the invention to be reached through routine experimentation or optimization within the prior art conditions set forth in Pavlakis, since Pavlakis teaches a priming step identical to the instantly recited priming step, and a boosting step that differs from the instantly recited boosting step only in that it is supplemented with a further administration of the priming composition. Furthermore, since all such compositions and steps are disclosed in the teachings of Pavlakis, one of ordinary skill in the art would have had a reasonable expectation of success in the absence of evidence to the contrary. Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 4-7, 9-10, 16-19, 21 and 47 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al. “Pavlakis” (WO2013/131099) in view of Sette et al. “Sette” (WO200124810), and further in view of Thomson et al. “Thomson” (WO200190197), Vinnik et al. “Vinnik” (WO2012055987), Scholler et al. “Scholler” (WO2010037402), Jiang et al. “Jiang” (CN102559724), Bahrami et al. “Bahrami” (WO2014166500), Han et al. “Han” (CN101469339), Walensky et al. “Walensky” (WO2010148335) and Baker et al. “Baker” (WO2005012502). The teachings of Pavlakis are outlined above and incorporated herein.
The claims are directed to a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide, wherein the HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22; and the conserved elements are separated by linkers of 1 to 5 amino acids in length.
Regarding claims 4-6, 9-10, 16-18, 21 and 47, Pavlakis teaches a method of HIV vaccination comprising administration of priming step comprising a nucleic acid encoding a first conserved element polypeptide that comprises at least 7 conserved elements from HIV-1 p24gag concurrent with administration of a nucleic acid construct encoding a second conserved element that comprises at least one variant of a conserved element differing by 1-3 amino acid (paragraphs [0007]-[0014]) (method of inducing: instant claims 4, 21). Pavlakis discloses a nucleic acid comprising the full-length polypeptide (e.g. Env and Gag), which encompasses the conserved elements of the protein (paragraphs [0011]) and [0017]) (instant claim 4). Pavlakis discloses in some embodiments, the elements encoded by the nucleic acid are arranged coilinearly. In some embodiments, the seven elements are separated by alanine linkers for efficient proteolytic cleavage (Figure 1D 1-5 amino acids) (linkers: instant claims 4, 16 and 47). In some embodiments, DNA. vectors are engineered to express the Core proteins (conserved element polypeptides comprising multiple conserved elements) only, to express secreted Core proteins having the N-terminal GM-CSF signal peptide (SPCore) (paragraph [0008]) (instant claims 9 and 10).
Pavlakis does not explicitly disclose SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22.
Sette, however, discloses Vaccine compositions comprising human immunodeficiency virus-1 (HIV-1) peptide groups, useful for vaccinating against HIV-1 and discloses peptides of the following: SEQ ID NO: 1 (claim 32 of Sette), SEQ ID NO: 2 (claim 32 of Sette), SEQ ID NO: 6 (claim 32 of Sette). Thomson discloses polypeptides for eliciting an immune response to HIV in a subject. Thomson discloses peptides of the following: SEQ ID NO: 4 (Example 1: Figure 12). Vinnik discloses peptides of HIV and discloses the following: SEQ ID NO: 8 (claim 1, SEQ ID NO: 4 of Vinnik), SEQ ID NO: 10 (claim 1, SEQ ID NO: 5 of Vinnik). Scholler discloses peptides for the treatment of HIV and discloses the following: SEQ ID NO: 12 (SEQ ID NO 8385 of Scholler). Jiang discloses recombinant fusion proteins and polypeptides for treating HIV and discloses the following: SEQ ID NO: 14 (claim 1, SEQ ID NO: 1 of Jiang), Bahrami discloses the use of peptides for treating HIV infection and discloses the following: SEQ ID NO: 16 (claim 36, SEQ ID NO: 257 of Bahrami), Han discloses HIV fusion proteins and discloses the following: SEQ ID NO: 18 (SEQ ID NO: 19 of Han). Walensky discloses peptides for treating HIV viral infection and discloses the following: SEQ ID NO: 20 (claim 5, SEQ ID NO: 24 of Walensky). Baker discloses peptide epitopes to HIV as candidates to eliciting an immune response and discloses the following: SEQ ID NO: 22 (pages 181-238 of Baker). (instant claims 4-6, 16-18, 21 and 47).
It would have been obvious to one of ordinary skill in the art to generate a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements as disclosed by Pavlakis, whereby the conserved elements from HIV (SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22) as disclosed by Sette, Thomson, Vinnik, Scholler, Jiang, Bahrami, Han, Walensky and Baker as the peptides were known in the prior art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that Pavlakis discloses a method of HIV vaccination comprising a nucleic acid encoding conserved element polypeptides and Sette, Thomson, Vinnik, Scholler, Jiang, Bahrami, Han, Walensky and Baker disclose known HIV peptide sequences, and demonstrate their immunogenicity as beneficial immunogenic peptides in the development and treatment of HIV infection. Furthermore, it would have been obvious to one of ordinary skill in the art to combine the conserved element sequences for the advantage of inducing a robust immune response in a subject. The courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 7 and 19, with respect to comprising a V1V2 region sequence, it is not inventive and considered routine and obvious to one of ordinary skill in the art to determine whether a construct comprises a variable region (e.g. V1V2) sequence as the Pavlakis discloses the effect of variable region sequence on immunogenicity. It is considered merely routine experimentation to determine the amount, if any, variable region sequences that are to be introduced in the resulting polypeptide.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 11-14 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al. “Pavlakis” (WO2013/131099) in view of Sette et al. “Sette” (WO200124810), and further in view of Mullins et al. “Mullins” (WO2008109059), Zolla-Pazner et al. “Zolla-Pazner” (WO2008005929), Dundr et al. “Dundr” (US PGPUB20060205070), Haynes et al. “Haynes” (WO2008033500), Phogat et al. “Phogat” (WO2011109511), Humbert et al. “Humbert” (WO2011022725), Lange et al. “Lange” (WO2012092934), Bahrami et al. “Bahrami-2” (WO2011077093), Braisted et al. “Braisted” (WO9820036) and Scholler et al. “Scholler” (WO2010037402). The teachings of Pavlakis are outlined above and incorporated herein.
The claims are directed to a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide, wherein the HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23; and the conserved elements are separated by linkers of 1 to 5 amino acids in length.
Regarding claims 11-13, Pavlakis teaches a method of HIV vaccination comprising administration of priming step comprising a nucleic acid encoding a first conserved element polypeptide that comprises at least 7 conserved elements from HIV-1 p24gag concurrent with administration of a nucleic acid construct encoding a second conserved element that comprises at least one variant of a conserved element differing by 1-3 amino acid (paragraphs [0007]-[0014]) (instant claim 11). Pavlakis discloses a nucleic acid comprising the full-length polypeptide (e.g. Env and Gag), which encompasses the conserved elements of the protein (paragraphs [0011]) and [0017]) (instant claim 11). Pavlakis discloses in some embodiments, the elements encoded by the nucleic acid are arranged coilinearly. In some embodiments, the seven elements are separated by alanine linkers for efficient proteolytic cleavage (Figure 1D 1-5 amino acids) (linkers: instant claim 11).
Pavlakis does not explicitly disclose SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23.
Sette, however, discloses Vaccine compositions comprising human immunodeficiency virus-1 (HIV-1) peptide groups, useful for vaccinating against HIV-1 and discloses peptides of the following: SEQ ID NO: 1 and SEQ ID NO: 17 (claim 32 of Sette). Mullins discloses conserved-element vaccines for HIV and discloses the following: SEQ ID NO: 3 (claim 16, SEQ ID NO: 58 of Mullins). Zolla-Pazner discloses recombinant HIV-1 peptides and discloses the following: SEQ ID NO: 5 (SEQ ID NO: 8 of Zolla-Pazner). Dundr discloses immunogenic peptides of HIV and discloses the following: SEQ ID NO: 7 (Figure 35B of Dundr). Haynes discloses compositions comprising polypeptides for inducing antibodies against HIV and discloses SEQ ID NO: 9 (Example 2; page 66). Phogat discloses HIV-1 gp120 protein and polypeptides for treatment of HIV-1 infection and discloses the following: SEQ ID NO: 11 (claim 1; Figure 9A-9I of Phogat). Humbert discloses expression vectors encoding HIV envelope polypeptides and discloses SEQ ID NO: 13 (SEQ ID NO: 582 of Humbert). Lange discloses peptides of HIV gp120 in immunogenic compositions and discloses SEQ ID NO: 15 (SEQ ID NO: 97 of Lange). Bahrami-2 discloses HIV viral protein and peptides and discloses SEQ ID NO: 19 (SEQ ID NO: 33 of Bahrami-2). Braisted discloses peptides from HIV for use in treatment against HIV and discloses SEQ ID NO: 21 (claim 11, page 191-192 of Braisted). Scholler discloses peptides for the treatment of HIV and discloses the following: SEQ ID NO: 23 (SEQ ID NO 8665 of Scholler) (instant claims 11-13).
It would have been obvious to one of ordinary skill in the art to generate a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements as disclosed by Pavlakis, whereby the conserved elements from HIV (SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23) as disclosed by Sette, Mullins (WO2008109059), Zolla-Pazner, Dundr, Haynes, Phogat, Humbert, Lange, Bahrami-2, Braisted and Scholler as the peptides were known in the prior art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that Pavlakis discloses a method of HIV vaccination comprising a nucleic acid encoding conserved element polypeptides and Sette, Mullins (WO2008109059), Zolla-Pazner, Dundr, Haynes, Phogat, Humbert, Lange, Bahrami-2, Braisted and Scholler disclose known HIV peptide sequences, and demonstrate their immunogenicity as beneficial immunogenic peptides in the development and treatment of HIV infection. Furthermore, it would have been obvious to one of ordinary skill in the art to combine the conserved element sequences for the advantage of inducing a robust immune response in a subject. The courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 14, with respect to comprising a V1V2 region sequence, it is not inventive and considered routine and obvious to one of ordinary skill in the art to determine whether a construct comprises a variable region (e.g. V1V2) sequence as the Pavlakis discloses the effect of variable region sequence on immunogenicity. It is considered merely routine experimentation to determine the amount, if any, variable region sequences that are to be introduced in the resulting polypeptide.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 22-25 and 27-40 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al. “Pavlakis” (WO2013/131099) in view of Sette et al. “Sette” (WO200124810), and further in view of Thomson et al. “Thomson” (WO200190197), Vinnik et al. “Vinnik” (WO2012055987), Scholler et al. “Scholler” (WO2010037402), Jiang et al. “Jiang” (CN102559724), Bahrami et al. “Bahrami” (WO2014166500), Han et al. “Han” (CN101469339), Walensky et al. “Walensky” (WO2010148335) and Baker et al. “Baker” (WO2005012502), Mullins et al. “Mullins” (WO2008109059), Zolla-Pazner et al. “Zolla-Pazner” (WO2008005929), Dundr et al. “Dundr” (US PGPUB2006205070), Haynes et al. “Haynes” (WO2008033500), Phogat et al. “Phogat” (WO2011109511), Humbert et al. “Humbert” (WO2011022725), Lange et al. “Lange” (WO2012092934), Bahrami et al. “Bahrami-2” (WO2011077093) and Braisted et al. “Braisted” (WO9820036). The teachings of Pavlakis are outlined above and incorporated herein.
The claims are directed to a method of inducing an immune response to HIV Env, the method comprising administering: a first nucleic acid encoding a first immunogenic HIV Env conserved element polypeptide that comprises at least five conserved elements selected from SEQ ID NO:1, 2,4, 6, 8, 10, 12, 14, 16, 18, 20, and 22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length; and a second nucleic acid encoding a second immunogenic HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length.
Regarding claims 22-24, 31, 33-35 and 40, Pavlakis discloses methods and compositions for eliciting immune responses by altering the immunodominance hierarchy of HIV GAG by expressing highly conserved elements from a virus (Abstract). Pavlakis teaches a method of HIV vaccination comprising administration of nucleic acids or of priming step comprising a nucleic acid encoding a first conserved element polypeptide that comprises at least 7 conserved elements from HIV-1 p24gag concurrent with administration of a nucleic acid construct encoding a second conserved element that comprises at least one variant of a conserved element differing by 1-3 amino acid (paragraphs [0007]-[0014]). Pavlakis further teaches boosting with the nucleic acid encoding the full-length protein concurrent with the conserved elements (paragraph [0066] and [0067]) (instant claim 31). Pavlakis discloses the CEs can be administered as one or more constructs (paragraph [0095]). Pavlakis discloses in some embodiments, the elements encoded by the nucleic acid are arranged coilinearly. In some embodiments, the seven elements are separated by alanine linkers for efficient proteolytic cleavage (Figure 1D 1-5 amino acids).
Pavlakis does not explicitly disclose SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22.
Sette, however, discloses Vaccine compositions comprising human immunodeficiency virus-1 (HIV-1) peptide groups, useful for vaccinating against HIV-1 and discloses peptides of the following: SEQ ID NO: 1 (claim 32 of Sette), SEQ ID NO: 2 (claim 32 of Sette), SEQ ID NO: 6 (claim 32 of Sette). Thomson discloses polypeptides for eliciting an immune response to HIV in a subject. Thomson discloses peptides of the following: SEQ ID NO: 4 (Example 1: Figure 12). Vinnik discloses peptides of HIV and discloses the following: SEQ ID NO: 8 (claim 1, SEQ ID NO: 4 of Vinnik), SEQ ID NO: 10 (claim 1, SEQ ID NO: 5 of Vinnik). Scholler discloses peptides for the treatment of HIV and discloses the following: SEQ ID NO: 12 (SEQ ID NO 8385 of Scholler). Jiang discloses recombinant fusion proteins and polypeptides for treating HIV and discloses the following: SEQ ID NO: 14 (claim 1, SEQ ID NO: 1 of Jiang), Bahrami discloses the use of peptides for treating HIV infection and discloses the following: SEQ ID NO: 16 (claim 36, SEQ ID NO: 257 of Bahrami), Han discloses HIV fusion proteins and discloses the following: SEQ ID NO: 18 (SEQ ID NO: 19 of Han). Walensky discloses peptides for treating HIV viral infection and discloses the following: SEQ ID NO: 20 (claim 5, SEQ ID NO: 24 of Walensky). Baker discloses peptide epitopes to HIV as candidates to eliciting an immune response and discloses the following: SEQ ID NO: 22 (pages 181-238 of Baker) (instant claim 22).
It would have been obvious to one of ordinary skill in the art to generate a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements as disclosed by Pavlakis, whereby the conserved elements from HIV (SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22) as disclosed by Sette, Thomson, Vinnik, Scholler, Jiang, Bahrami, Han, Walensky and Baker as the peptides were known in the prior art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that Pavlakis discloses a method of HIV vaccination comprising a nucleic acid encoding conserved element polypeptides and Sette, Thomson, Vinnik, Scholler, Jiang, Bahrami, Han, Walensky and Baker disclose known HIV peptide sequences, and demonstrate their immunogenicity as beneficial immunogenic peptides in the development and treatment of HIV infection. Furthermore, it would have been obvious to one of ordinary skill in the art to combine the conserved element sequences for the advantage of inducing a robust immune response in a subject. The courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Pavlakis does not explicitly disclose SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23.
Sette, however, discloses Vaccine compositions comprising human immunodeficiency virus-1 (HIV-1) peptide groups, useful for vaccinating against HIV-1 and discloses peptides of the following: SEQ ID NO: 1 and SEQ ID NO: 17 (claim 32 of Sette). Mullins discloses conserved-element vaccines for HIV and discloses the following: SEQ ID NO: 3 (claim 16, SEQ ID NO: 58 of Mullins). Zolla-Pazner discloses recombinant HIV-1 peptides and discloses the following: SEQ ID NO: 5 (SEQ ID NO: 8 of Zolla-Pazner). Dundr discloses immunogenic peptides of HIV and discloses the following: SEQ ID NO: 7 (Figure 35B of Dundr). Haynes discloses compositions comprising polypeptides for inducing antibodies against HIV and discloses SEQ ID NO: 9 (Example 2; page 66). Phogat discloses HIV-1 gp120 protein and polypeptides for treatment of HIV-1 infection and discloses the following: SEQ ID NO: 11 (claim 1; Figure 9A-9I of Phogat). Humbert discloses expression vectors encoding HIV envelope polypeptides and discloses SEQ ID NO: 13 (SEQ ID NO: 582 of Humbert). Lange discloses peptides of HIV gp120 in immunogenic compositions and discloses SEQ ID NO: 15 (SEQ ID NO: 97 of Lange). Bahrami-2 discloses HIV viral protein and peptides and discloses SEQ ID NO: 19 (SEQ ID NO: 33 of Bahrami-2). Braisted discloses peptides from HIV for use in treatment against HIV and discloses SEQ ID NO: 21 (claim 11, page 191-192 of Braisted). Scholler discloses peptides for the treatment of HIV and discloses the following: SEQ ID NO: 23 (SEQ ID NO 8665 of Scholler) (instant claims 11-13). With respect to claims 33-35 and 40, the claims are methods of administering the polypeptide rather than a nucleic acid construct; however, it is not inventive and considered conventional, routine and obvious such that one of ordinary skill in the art would readily utilize well-known molecular techniques to express the polypeptides in vitro prior to administering to a subject.
It would have been obvious to one of ordinary skill in the art to generate a nucleic acid encoding an immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements as disclosed by Pavlakis, whereby the conserved elements from HIV (SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23) as disclosed by Sette, Mullins (WO2008109059), Zolla-Pazner, Dundr, Haynes, Phogat, Humbert, Lange, Bahrami-2, Braisted and Scholler as the peptides were known in the prior art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that Pavlakis discloses a method of HIV vaccination comprising a nucleic acid encoding conserved element polypeptides and Sette, Mullins (WO2008109059), Zolla-Pazner, Dundr, Haynes, Phogat, Humbert, Lange, Bahrami-2, Braisted and Scholler disclose known HIV peptide sequences, and demonstrate their immunogenicity as beneficial immunogenic peptides in the development and treatment of HIV infection. Furthermore, it would have been obvious to one of ordinary skill in the art to combine the conserved element sequences into nucleic acid constructs for the advantage of inducing a robust immune response in a subject utilizing one or more constructs as disclosed by Pavlakis (paragraph [0095]) (instant claims 22-24, 31, 33-35 and 40). The courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 25, with respect to comprising a V1V2 region sequence, it is not inventive and considered conventional, routine and obvious to one of ordinary skill in the art to determine whether a construct comprises a variable region (e.g. V1V2) sequence as the Pavlakis discloses the effect of variable region sequence on immunogenicity. It is considered merely routine experimentation to determine the amount, if any, variable region sequences that are to be introduced in the resulting polypeptide.
Regarding claims 27-28, Pavlakis discloses the nucleic acid sequences can be contained in separate or same expression vectors (claims 12 and 13 of Pavlakis).
Regarding claims 29-30 and 38-39, Pavlakis discloses the nucleic acids can be administered sequentially or concurrently (claims 9 and 10 of Pavlakis).
Regarding claim 32, Pavlakis discloses the constructs are administered intramuscularly by in vivo electroporation (claim 15 of Pavlakis).
Regarding claim 36, with respect to comprising a V1V2 region sequence, it is not inventive and considered routine and obvious to one of ordinary skill in the art to determine whether a construct comprises a variable region (e.g. V1V2) sequence as the Pavlakis discloses the effect of variable region sequence on immunogenicity. It is considered merely routine experimentation to determine the amount, if any, variable region sequences that are to be introduced in the resulting polypeptide.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672