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 .
Election/Restrictions
Applicant’s election without traverse of Group 2 (a method for reducing or preventing anthrax infection) and the species of (1) both lethal factor and protective antigen and (2) SEQ ID NO: 2 in the reply filed on 13 July 2026 is acknowledged.
Claim Status
The amended claim set filed 21 Aug 2026 is acknowledged. Claims 1, 13, 17-18, 20-21, 25-26, and 29-39 are currently pending. Of those, claims 13, 17, and 25-26 are currently amended, and claims 29-39 are new. Claims 1, 17-18, 20-21, and 25-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 13 July 2026. Claims 2-12, 14-16, 19, 22-24, and 27-28 are cancelled. Claims 13 and 29-39 will be examined on the merits herein.
Priority
The instant application claims priority to provisional application 63/284,841 (filed 1 Dec 2021) and is a 371 of PCT/US2022/080759 (filed 1 Dec 2022). The effective filing date used for searching the art is 1 Dec 2021 for all claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 21 May 2025, 4 Feb 2026, and 28 May 2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. Signed copies of these statements are attached with this action.
References to the Specification
To avoid ambiguity if future amendments to the specification change the page and line numbers where information is located, in this action references to the specification will use paragraph numbers from the Pre-Grant Publication US-20250152692-A1 (PTO-892).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 13 and 29-39 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 13, the claim recites “an immunogenic composition or a vaccine comprising thereof”. The specification defines that the term “vaccine” is a narrower limitation than “immunogenic composition” because it has additional functional requirements (“The term “vaccine,” as used herein, refers to any pharmaceutical composition containing at least one immunogen, which composition can be used to prevent or treat a disease or condition in a subject.” [0045). Also, the use of the term “vaccine comprising thereof” creates confusion because “thereof” refers to the object prior, but the prior term (comprising) is a verb rather than a noun.
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). The claim(s) are 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. Therefore, the claim is indefinite because the claim uses two different terms with broader and narrower claim breadths and because there is not a clear object being pointed to by the term “thereof”. Claims 29-39 are also rejected because they depend from claim 13 and do not obviate this grounds of rejection. In the interest of compact prosecution, the claim will be interpreted with the broader genus of “administering … an immunogenic composition comprising”. It is believed that the intent of “thereof” was to claim a vaccine with the same structural features as the immunogenic composition, so the broader genus of administering an immunogenic composition also addresses this source of indefiniteness.
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 13 and 29-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Claim 13 recites a method for reducing or preventing anthrax infection in a subject in need thereof, comprising administering to the subject an effective amount of the an immunogenic composition or a vaccine comprising thereof, wherein the immunogenic composition comprises each of: an antigenic Bacillus anthracis lethal factor peptide: and an antigenic Bacillus anthracis protective antigen peptide (as well as other, nonelected species of compositions). Claims 29 and 30 recite that the protective antigen peptide and lethal factor peptide comprise SEQ ID NOs: 1 and 2, respectively. Claim 31, given the species election, also recites that the lethal factor peptide comprises SEQ ID NO: 2; note that claim 32 makes clear that there is no limitation requiring that the antigenic peptide sequence be an isolated peptide rather than part of a larger protein (claim 32 is not rejected; cited for claim interpretation only).
Walsh et al. (2007; PTO-892) teaches a subject who experienced a naturally acquired infection from inhaling anthrax (Title). Walsh teaches that the subject had serum lethal factor (LF) and had raised antibodies targeting anthrax protective antigen (PA) (Figure 1). Therefore, the subject was naturally administered (i.e. infection via inhalation) an immunogenic composition comprising both lethal factor and protective antigen (i.e. the bacteria that was inhaled, which is immunogenic because it caused antibody production). The subject survived (pg. 970 col. 1 par. 1) and it is presumed that the natural infection is capable of preventing future anthrax infections, absent evidence to the contrary, because it is the same product that is claimed and is used in the same manner that is claimed. See MPEP 2111.02.II: “ To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997)”. See MPEP 2112.01: “"When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.”
Regarding SEQ ID NOs: 1-2, Walsh does not explicitly teach the sequences of the protective antigen and lethal factor that were secreted by the B. anthracis that was in the infection. But the instant application teaches that these sequences are part of the same protective antigen and lethal factor that were present in the Walsh subject (see text of claims 29-31), so the claimed sequences are presumed to be present because the same protein source is administered by the natural infection and there is no reason to believe that those peptides were not present in the naturally administered protective antigen and lethal factor. See MPEP 2112.01: “"When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.”
This judicial exception (the natural administration via infection) is not integrated into a practical application because the administration step and effect on the subject both occur naturally so there are no additional elements that could integrate into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the administration step and effect on the subject both occur naturally so there are no additional elements that could amount to significantly more.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 13 and 29-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walsh et al. (2007; hereafter Walsh; PTO-892).
Regarding claim 1, Walsh teaches a subject who experienced a infection from inhaling anthrax (Title). Walsh teaches that the subject had serum lethal factor (LF) and had raised antibodies targeting anthrax protective antigen (PA) (Figure 1). Therefore, the subject was naturally administered (i.e. infection) an immunogenic composition comprising both lethal factor and protective antigen (i.e. the bacteria that was inhaled, which is immunogenic because it caused antibody production). The subject survived (pg. 970 col. 1 par. 1) and it is presumed that the natural infection is capable of preventing future anthrax infections, absent evidence to the contrary, because it is the same product that is claimed and is used in the same manner that is claimed. See MPEP 2111.02.II: “ To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997)”. See MPEP 2112.01: “"When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.”
Regarding claims 29-31 and SEQ ID NOs: 1-2, claim 31, given the species election, also recites that the lethal factor peptide comprises SEQ ID NO: 2; note that claim 32 makes clear that there is no limitation requiring that the sequence be an isolated peptide rather than part of a larger protein (claim 32 is not rejected; cited for claim interpretation only). Walsh does not explicitly teach the sequences of the protective antigen and lethal factor that were secreted by the B. anthracis that was in the infection. But the instant application teaches that these sequences are part of the same protective antigen and lethal factor that were present in the Walsh subject (see text of claims 29-31), so the claimed sequences are presumed to be present because the same protein source is administered by the natural infection and there is no reason to believe that those peptides were not present in the naturally administered protective antigen and lethal factor. See MPEP 2112.01: “"When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.”
Claims 13, 32-35, and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Katrich et al. (US-20030235818-A1, 2003; hereafter Katrich; IDS filed 21 May 2025).
Regarding claims 13, 32-34, Katrich teaches identifying immunogenic epitopes from target proteins [0009] and that the target protein that epitopes are immunogenic peptides derived from Bacillus anthracis protective antigen (PA), lethal factor (LF), or both [0013]. Katrich teaches that the epitopes are linked to scaffold proteins [0010] that can be assembled to form a virus-like particle [0011]. Katrich also teaches a method of stimulating an immune response by administering the immunogenic peptide, including teaching that “the subject is a human subject exposed to or at risk of exposure to B. anthracis, and administration of the immunogenic peptide generates a protective immune response in the subject against the signs and symptoms of anthrax.” [0023-0024]. Specifically, in examples, Katrich teaches small structural domains of PA and LF should be used in combination with an effective VLP delivery system [0132], specifically, a hepatitis B core scaffold protein [0134].
Katrich teaches that another study found “significant synergy between PA and Lethal Factor B-cell epitopes. The combination of PA and LF immunogens induces up to five times more antibodies in mice compared to either gene alone, and confers improved protection (refs 21, 22). Moreover, a very recent passive immunization study by Kobiler et. al has demonstrated that, while anti-PA antibodies play a major role in protection against anthrax spore infection, it is anti-LF antibodies that most effectively protect against the lethal toxin itself (ref 23).” [0131].
Regarding claim 35, Katrich teaches that the PA and LF can be individually inserted into VLPs [0186] and teaches homogenous VLPs, with PA and LF individually inserted within them, that are mixed prior to administration [0194, 0204, 0216].
Regarding claim 39, Katrich teaches that the immunogenic peptide can be formulated with an adjuvant [0021, 0023]. In the examples, the composition is formulated with adjuvant [0158].
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 13, 29, 32-35, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Katrich et al. (US-20030235818-A1, 2003; hereafter Katrich; IDS filed 21 May 2025) in view of Oscherwitz et al. (2010; hereafter Oscherwitz; IDS filed 21 May 2025).
The teachings of Katrich were discussed above and include all limitations of claims 13, 32-35, and 39. Briefly, Katrich teaches vaccines comprising PA and LF linked to VLP scaffold proteins, which are used to immunize against B. anthracis. Additionally, Katrich teaches that the use of both full-length proteins in a vaccine would be hazardous because the proteins would form a functional toxin [0132]. Instead, Katrich used fragments that should not exceed 250 residues [0171], and specifically regions that can be detached and effective as a stand-alone antigen [0137].
Katrich does not teach that the PA peptide comprises SEQ ID NO: 1, as in claim 29.
Oscherwitz teaches a method of vaccinating against anthrax, where the vaccine is aa 304–319 from the loop-neutralizing determinant (LND) of Bacillus anthracis protective Ag (PA) fused to a carrier that is a heterologous T cell epitope from Plasmodium falciparum (Abstract) and that is administered with an adjuvant (“in an emulsion with CFA”, pg. 3662 col. 1 par. 4). Oscherwitz teaches that the sequence of aa 304–319 is single-letter code: HGNAEVHASFFDIGGS (pg. 3662 col. 1 par. 3), which is identical to SEQ ID NO: 1 (HGNAEVHASFFDIGGS) by inspection. Oscherwitz teaches that the antigen is protective in rabbits exposed to inhalation anthrax (Title, Abstract). “All rabbits with prechallenge TNA titers survived the aerosol challenge.” (pg. 3665 col. 1 par. 2).
Oscherwitz teaches many advantages to this peptide of LND as a vaccine: “Development of a synthetic peptide vaccine against anthrax could offer potential advantages with regard to safety, reactigenicity, and ease of vaccine manufacture, administration, and storage, compared with other PA-based vaccine formulations. Moreover, because Ab to the LND is capable of mediating protection from lethal spore challenges with B. anthracis, yet appears unlikely to be present at meaningful concentrations in the sera of AVA or AVP human vaccinees, immunization with a synthetic peptide vaccine capable of eliciting Ab to the LND may enhance the efficacy and robustness of PA-based vaccination. Finally, a synthetic peptide vaccine that effectively targets this cryptic epitope could also be strategic in countering malicious attempts to engineer PA to escape neutralizing specificities elicited by AVA and AVP, and other PA-based vaccines and therapeutics (35, 60, 61). The linear sequences comprising the LND, which are found within the 2β2–2β3 loop of PA, are critical to the translocation of LF and EF into the cytosol, and mutations or deletions in this region, especially those involving the F313–F314, have been shown to completely abrogate the cytotoxicity of LeTx in vitro (38–41, 62). The criticality of these loop sequences for LeTx cytotoxicity might hinder any malicious re-engineering of PA to subvert an LND vaccine.” (par. bridging pg. 3666-3667).
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to improve the Katrich method of vaccinating against anthrax by using a PA-VLP by using the fragment of SEQ ID NO: 1 to raise a protective immune response against PA as taught by Oscherwitz, thereby arriving at the claimed invention, because the use of this PA fragment as an antigen will be desirable for the many reasons provided in Oscherwitz. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.” The modification could be made with a reasonable expectation of success because both Katrich and Oscherwitz teach the molecular biology techniques required to insert the SEQ ID NO: 1 PA peptide into the VLP of Katrich, and because Oscherwitz teaches that the SEQ ID NO: 1 PA peptide raises protective immunity when used as a fusion protein with a carrier protein (the Plasmodium falciparum epitope).
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art (Katrich) teaches a method that only differs from the claimed invention by the substitution of a single component (i.e. substitution of the PA antigen used); the substituted element (i.e. the SEQ ID NO: 1 antigen) was already known and already shown to function as a PA antigen that can be administered in an immunogenic composition to prevent anthrax infection, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting one peptide for another with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 13, 30-35, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Katrich et al. (US-20030235818-A1, 2003; hereafter Katrich; IDS filed 21 May 2025) in view of Yusibov et al. (US-20110142870-A1, 2011; hereafter Yusibov; PTO-892).
The teachings of Katrich were discussed above and include all limitations of claims 13, 32-35, and 39. Briefly, Katrich teaches vaccines comprising PA and LF linked to VLP scaffold proteins, which are used to immunize against B. anthracis. Additionally, Katrich teaches that the use of both full-length proteins in a vaccine would be hazardous because the proteins would form a functional toxin [0132]. Instead, Katrich used fragments that should not exceed 250 residues [0171], and specifically regions that can be detached and effective as a stand-alone antigen [0137].
Katrich does not teach that the lethal factor peptide comprises SEQ ID NO: 2, as in claims 30-31. Claim 31, given the species election, also recites that the lethal factor peptide comprises SEQ ID NO: 2; note that claim 32 makes clear that there is no limitation requiring that the sequence be an isolated peptide rather than part of a larger protein (claim 32 is cited here for claim interpretation only).
Yusibov teaches vaccines used to prevent B. anthracis infection [Abstract] and methods of administering it to a subject in need thereof [0150, 0154]. Yusibov teaches a lethal factor sequence that comprises SEQ ID NO: 2 [0031, see figure 1 below]. SEQ ID NO: 2 corresponds with the peptide with aa342-361 of the mature polypeptide [see figure 1 below]. Yusibov teaches that the peptide of instant SEQ ID NO: 2 is in domain 4 (aa306-385 of the mature polypeptide) [0031]. Yusibov teaches that domain 4 of LF can be used as an antigen [0037, claim 32]. Yusibov teaches that antigens can be delivered by “carrier proteins [that] have the potential to assemble and form recombinant virus-like particles displaying a desired antigenic epitopes on their surface. This approach allows for time-efficient production of vaccine candidates, since the particulate nature of a vaccine candidate facilitates easy and cost-effective recovery from plant tissue. Additional advantages include enhanced target-specific immunogenicity, potential to incorporate multiple vaccine determinants, and ease of formulation into vaccines that can be delivered nasally, orally or parenterally.” [0049]. Yubisov also teaches that the vaccines can comprise adjuvants [0159].
Figure 1: Copy of Yusibov with highlight indicating the location of SEQ ID NO: 2 (top) and an alignment (below) demonstrating what amino acid residues correspond with instant SEQ ID NO: 2.
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One of ordinary skill in the art at the time of filing would consider it prima facie obvious to improve the Katrich method of vaccinating against anthrax that uses a LF-VLP with a generic immunogenic LF antigen by instead using domain 4, including the SEQ ID NO: 2 antigen, to raise a protective immune response against LF as taught by Yusibov, thereby arriving at the claimed invention, because Yusibov teaches that this protein fragment can be used in VLPs like those of Katrich to produce a time efficient and cost effective vaccine. This choice would also be beneficial because Katrich does not identify specific parts of the LF protein that should be used and choosing a LF fragment from the art would reduce experimentation. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.” The modification could be made with a reasonable expectation of success because both Katrich and Yusibov teach the molecular biology techniques required to insert the SEQ ID NO: 2 LF peptide into the Katrich VLP, and because Yusibov teaches that the SEQ ID NO: 2 LF peptide can be used on a VLP.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art (Katrich) teaches a method that only differs from the claimed invention by the substitution of a single component (i.e. substitution of the LF antigen used); the substituted element (i.e. the SEQ ID NO: 2 antigen) was already known and already taught to function as a LF antigen that can be administered in an immunogenic composition to prevent anthrax infection, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting one peptide for another with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 13, and 32-39 are rejected under 35 U.S.C. 103 as being unpatentable over Katrich et al. (US-20030235818-A1, 2003; hereafter Katrich; IDS filed 21 May 2025) in view of Milich et al. (US-20050025782-A1, 2005; hereafter Milich; PTO-892).
The teachings of Katrich were discussed above and include all limitations of claims 13, 32-35, and 39. Briefly, Katrich teaches vaccines comprising PA and LF linked to hepatitis B core VLP scaffold proteins, which are used to immunize against B. anthracis.
Katrich does not teach that the polypeptide capable of forming a virus like particle is a woodchuck hepatitis DNA virus core antigen, as in claim 36; that the amino acid sequence of the woodchuck hepatitis DNA virus core antigen comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 6, as in claim 37; or that insertion in the amino acid sequence of the woodchuck hepatitis DNA virus core antigen is at position 78 of SEQ ID NO: 6, as in claim 38.
Milich teaches “recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.” [Abstract]. Milich teaches that human hepatitis B virus (HBV) core protein (HBcAg) has been utilized as a carrier platform in the art, but that the existing technology has limitations including “less than 50% of foreign epitopes can be accommodated by the HBcAg platform because of adverse effects on particle assembly (Jegerlehner et al., Vaccine, 20:3104, 2002 and PCT/US01/25625); use of the HBcAg compromises the use of the anti-HBc diagnostic assay; and immune tolerance to HBcAg in individuals chronically infected with HBV (300-400 million worldwide) limits immunogenicity in this population.” [0004]. To improve those issues, Milich uses woodchuck hepatitis virus core antigen “in a preferred embodiment” [0011] to make an immunogenic composition where a heterologous antigen is inserted within the hepatitis virus core antigen [0011]. The woodchuck hepadna virus (WHV) core antigen is abbreviated WHcAg [0066]. Milich teaches the amino acid sequence for wild-type WHcAg is SEQ ID NO: 1 and truncated WHcAg is SEQ ID NO: 38 [0063, Figure 40]. As shown in Figures 2-3 below, both sequences have at least 70% identity to instant SEQ ID NO: 6 and full-length WHcAg is identical to instant SEQ ID NO: 6. WHcAg assembles into virus-like particles, including when epitopes are inserted into the sequence [0310]. Milich teaches that an epitope may be inserted into WHcAg into position 78, and that this insertion position is more immunogenic than other insertion positions [0039, Figure 16, 0314]. Milich also teaches that the WHcAg platform can be used to vaccinate against anthrax antigens [0206].
Figure 2: Alignment of instant SEQ ID NO: 6 with Milich full-length woodchuck hepatitis virus (SEQ ID NO: 1). The proteins have more than 70% identity.
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Figure 3: Alignment of instant SEQ ID NO: 6 with Milich truncated woodchuck hepatitis virus (SEQ ID NO: 38). The proteins have more than 70% identity.
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One of ordinary skill in the art at the time of filing would consider it prima facie obvious to improve the Katrich method of vaccinating against anthrax using PA and LF antigens in VLP form that uses hepatitis B as a carrier protein by instead using woodchuck hepatitis virus core antigen as the carrier protein disclosed in Milich and using position 78 for inserting the antigen, thereby arriving at the claimed invention, because Milich teaches that woodchuck hepatitis virus core antigen is a desirable improvement on the existing work using hepatitis B virus core protein with better outcomes in subjects who are or may become infected with hepatitis B, and also teaches that the insertion into position 78 is desirable to increase immunogenicity. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.” The modification could be made with a reasonable expectation of success because Milich specifically promotes using woodchuck hepatitis virus core antigen in place of hepatitis B virus core protein, because both Katrich and Milich teach the molecular biology techniques required to generate VLP vaccines, and because Milich teaches that woodchuck hepatitis virus core antigen can be used with anthrax antigens.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case all elements (i.e. methods of administering PA- and LF-VLP vaccines from Katrich, using woodchuck hepatitis in place of hepatitis B virus for VLP vaccines from Milich, using the antigen insertion site of position 78 from Milich) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowed.
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AMELIA N DICKENS
Examiner
Art Unit 1645
/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
Prosecution Insights