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
Claim Status
Claims are 1-2, 6, 8-10, 13-14, 16-17, 19-20, 22-23, and 25-29 are pending. Claims 6, 14, 19-20, 22-23, and 25-29 are withdrawn. Claims 1-2, 8-10, 13, and 16-17 are under examination on the merits.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-2, 6, 8-10, 13-14, and 16-17, and the required species, a specific form of CVB: inactivated viral particles (IVPs), and specific CVB serotypes presents in the composition: the combination of all five serotypes, namely CVB1, CVB2, CVB3, CVB4, and CVB5, in the reply filed on 8/5/2026 is acknowledged. The traversal is on the ground(s) that it would not be unduly burdensome to perform a search on all of the claims together in the present application. This is not found persuasive because: it states the inapposite legal standard, this application is a national stage application of a PCT application, in which restriction is proper when there is a lack of unity of invention, as demonstrated in the restriction requirement filed 6/11/2026, rather than undue burden.
The requirement is still deemed proper and is therefore made FINAL.
Claims 19-20, 22-23, and 25-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, and claims 6 and 14 are withdrawn from further consideration as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/5/2026.
Claims 1-2, 8-10, 13, and 16-17 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 2/5/2025 and 1/20/2026 are in compliance with 37 CFR 1.97. Accordingly, the references listed in the IDSs are being considered by the examiner.
Specification – Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) as follows:
The specification does not contain sequence identifiers (SEQ ID NO:) in all locations where sequences are disclosed, see e.g. FIG. 1. To correct this, the sequences in figures can be referred to in either the figure or the Brief Description of Drawings. If the prior filed Sequence Listing does not contain updated sequences, Applicant is also required to submit a replacement Sequence Listing that includes all updated sequences.
Full compliance with the sequence rules is required in response to this Office Action. A complete response to this office action should include both compliance with the sequence rules and a response to the Office Action set forth below. Failure to fully comply with both these requirements in the time period set forth in this Office Action will be held non-responsive.
Claim Objections
Claims 1, 8, and 9 are objected to because of the following informalities: claims 1, 8, and 9 recite “is the form of” in line 2, but should instead recite “is in the form of”. Appropriate correction is required.
Claims 2 and 10 are objected to because of the following informalities: on lines 15 (claim 2) and 14 (claim 10), they recite “e) CVB5 in an amount of from 6.0 x 107 IVP to 6.0 x 107 IVP”. To be in better form, the claims should instead recite “e) CVB5 in an amount of 6.0 x 107 IVP”. 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 1-2, 8-10, 13 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claims recite “[a] composition comprising coxsackievirus B (CVB) of from two to five serotypes, wherein the CVB is the form of inactivated viral particles (IVP), viral-like particles (VLP), one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides” (claims 1 and 8). This judicial exception is not integrated into a practical application because “inactivated viral particles (IVP), viral-like particles (VLP), one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides” read on naturally occurring coxsackieviruses and their protein or nucleic acids.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because though the composition requires a combination of from two to five serotypes, that could also occur naturally in an infected cell, subject, or milieu. Additionally, combination of two or more components does not change the structure and properties of the components, and is not markedly different from the naturally occurring products which are a “product of nature” exception. Similarly, while the claims encompass “inactivated viral particles”, the specification indicates that “inactivated” means that the infectivity of the virus has been reduced or eliminated, which would be a natural consequence of natural mutation within the virus or incompletely formed particles that occur naturally during infection while assembling and maturing. Additionally, claim 17 requires the composition to comprise an adjuvant and/or saline, that is not an additional element that is sufficient to amount to significantly more because sodium and chloride are major electrolytes of the fluid compartment outside of the cells, and sodium chloride is present in a 70-kg person at an amount of ~100g, 60% of which is in the fluid inside and outside of cells (“Sodium (Chloride)”, Linus Pauling Institute, published 4/11/2019, accessed at https://lpi_oregonstate_edu/mic/minerals/sodium on 9/9/2026, pp. 1 & 3). Therefore, natural CVB and its polypeptide and polynucleotide components would be present in saline solutions.
35 U.S.C. § 112(b) – Indefiniteness
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 1-2, 8-10, 13 and 16-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 2, 9, 10, and 13 recite “an equivalent amount of VLP, one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides.” The term “equivalent” in claims 1, 2, 9, 10, and 13 is a relative term which renders the claims indefinite. The term “equivalent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear which amount of VLPs, polypeptides, or polynucleotides is required to be an “equivalent amount”. For example, it is not clear if the “equivalent amount” refers to weight, molecule number, etc. Claims 16-17 depend on claim 1 but do not resolve this lack of clarity, and are thus also indefinite and rejected herein.
Claim 8 recites “induces viral neutralizing antibody titer (VNT) of from 1/8 to 1/64,000 as determined by a VNT assay” on lines 5-6. The specification explains that “viral neutralizing antibody titer” refers to the highest dilution of the sample which still neutralizes the infectivity of the virus in cell culture (spec., para. [00121-122]. Claim 8 is a composition comprising CVB of from two to five serotypes, but the claim is indefinite because it is not clear for which (or all) viral serotypes the serum must meet the required threshold of VNT of from 1/8 to 1/64,000 in order to read on the claimed composition. Thus, the metes and bounds of the claim are unclear, and claim 8 is indefinite. Claims 9-10 and 13 depend on claim 8 but do not resolve this lack of clarity, and thus are also indefinite.
Claim Rejections - 35 USC § 112
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.
Written Description
Claims 8-10 and 13 are 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.
“[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.
Furthermore, to satisfy the written description requirement for the genus compositions comprising CVB of from two to five serotypes that when administered to an individual induces VNT of from 1/8 to 1/64,000 as determined by a VNT assay, Applicant must adequately describe representative compositions to reflect the structural diversity of the claimed genus. See Eli Lilly, 119 F.3d at 1568 (“[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.”).
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 compositions claimed are not limited to discrete structures, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” One of skill in this art cannot envision the structure of compositions comprising CVB of from two to five serotypes that when administered to an individual induces VNT of from 1/8 to 1/64,000 as determined by a VNT assay. The specification discloses a number of VNTs for CVB1-CVB5 following vaccination (Figs. 2-14 and 17-18) with PRV101, a composition comprising CVB IVPs from serotypes 1 through 5 (Examples 1 and 2; Figs. 2-14 and 17-18). However, the specification does not appear to disclose any VNTs near the upper end of the claimed range of 1/64,000, and it is not apparent that the claimed compositions are capable of generating such a potent neutralizing antibody response. Therefore, since limited species are provided to represent these genera, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
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) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus. The disclosure does not provide examples of other compositions (VLPs, polypeptides, or nucleic acids encoding CVB polypeptides) that confer the required function.
The instant claims above are drawn to a genus of compositions comprising coxsackievirus B (CVB) of from two to five serotypes, wherein the CVB is in the form of inactivated viral particles (IVP), a CVB viral-like particle (VLP), one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides wherein the composition, when administered to an individual, induces viral neutralizing antibody titer (VNT) of from 1/8 to 1/64,000 as determined by a VNT assay, wherein the composition does not include CVB6 (claim 8).
Even if the prior art is aware of such compositions comprising CVB of from two to five serotypes that when administered to an individual induces VNT of from 1/8 to 1/64,000 as determined by a VNT assay, the totality of known CVB compositions would not be representative of the entire genus for the reasons discussed below.
Disclosure in the instant specification
The specification teaches examples of experiments on inducing host immune response by administration of CVB antigen compositions. See Examples beginning from paragraph [00393]. These examples are based on IVPs which are shown to induce host immune response. The specification does not provide information on how other claimed forms of CVB antigens, i.e., VLPs, one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides, are administered to induce host immune response. The specification does not disclose how CVB VLPs can be produced that are capable of inducing host immune response, and which CVB viral polypeptides and/or nucleic acid encoding them can be used in the induction of host immune response, let alone administering them to induce host neutralizing immune response to the level as claimed.
State of the art at the time of invention
It is known in the art that VLPs can be produced from CVB structural proteins VP1-4, and that VLPs can induce significant levels of host immune response. See e.g. Hankaniemi et al. (Microorganisms 2020, 8, 1287), pages 3 and Fig. 3.
Based on the analysis above, a representative number of species has not been taught to describe these genera; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of compositions comprising coxsackievirus B (CVB) of from two to five serotypes, wherein the CVB is in the form of inactivated viral particles (IVP), a CVB viral-like particle (VLP), one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides wherein the composition, when administered to an individual, induces viral neutralizing antibody titer (VNT) of from 1/8 to 1/64,000 as determined by a VNT assay, wherein the composition does not include CVB6. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
While applicant has described one or a few species within each of the genera recited, and the art may provide more, the genus is large and would encompass structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the structures encompassed by the claimed genera only defined by function. Any future CVB composition structure 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 recited genera of recombinant vectors encoding chimeric spike proteins. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The specification does not provide sufficient guidance on how the other antigen forms in the generic scope as claimed can be reduced to practice. Accordingly, the specification does not provide written description support that the Applicant is in possession of the invention in the generic form as claimed.
Scope of Enablement
Claims 8-10 and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition comprising CVB antigens in the form of inactivated viral particles, a CVB viral-like particle (VLP), when administered to an individual induces VNT of from 1/8 to 1/64,000 as determined by a VNT assay, does not reasonably provide enablement for compositions of CVB polypeptides or nucleic acids that induce VNT of from 1/8 to 1/64,000 against any CVB strain. 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 or use the invention commensurate in scope with these claims.
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention, 5) the state of the prior art, 6) the relative skill of those in the art, 7) the predictability of the art, and 8) the breadth of the claims. Id. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
The breadth of the claims is highly generic, comprising all forms of possible CVB antigens.
The nature of the invention is a composition comprising coxsackievirus B (CVB) of from two to five serotypes, wherein the CVB is in the form of inactivated viral particles (IVP), a CVB viral-like particle (VLP), one or more CVB polypeptides, or one or more nucleic acids comprising nucleotide sequences encoding the one or more CVB polypeptides wherein the composition, when administered to an individual, induces viral neutralizing antibody titer (VNT) of from 1/8 to 1/64,000 as determined by a VNT assay, wherein the composition does not include CVB6 (claim 8). The claims also encompass compositions with CVB in the form of IVPs at various amounts in particular volumes (claims 9-10 and 13).
The level of skill of one skilled in this art is high, requiring a researcher to understand the biology of the CVB viruses as well as viral antigen characterization, host immunology and vaccine development.
Teachings in the specification as well as knowledge in the art are described above in the written description section above. Additionally, the specification teaches induction of VNT in human subjects administered CVB of serotypes 1-5, in the amounts of CVB1: 3.3x107 IVP, CVB2: 1.1x107 IVP, CVB3: 1.5x108 IVP, CVB4: 3.2x107 IVP, and CVB5: 6.3x107 IVP (low dose, 100 µL) or CVB1: 1.6x108, CVB2: 5.5x107 IVP, CVB3: 7.5x108 IVP, CVB4: 1.6x108 IVP, CVB5: 3.1x108 IVP (high dose, 500 µL; spec., pp. 33-36; Fig. 2; Figs. 3-16). Additionally, the specification discloses some cross-reactivity against CVB6, but none for CAV9 serotypes (Example 3; Figs. 17-18). These teachings do not enable the full breadth of the claims because Applicant does not show data with VLPs, CVB polypeptides, or nucleic acids encoding CVB polypeptides, nor does it disclose VNT for CVB serotypes others than those administered to the subject, or data related to other strains. It would require undue experimentation for a person having ordinary skill in the art to make and use the full breadth of the claims.
The state of the prior art is such that it is well established in the art that the CVB specific neutralizing antibodies may be elicited by administration of inactivated CVB (Stone et al., Sci. Adv. 2020; 6:33aaz2433, published 5/6/2020, on IDS), or CVB sub-unit vaccines (Hyoty, et al. US Patent No. 7090855 B1, issued 8/15/2006). Notably, serotype specific vaccines may include one or more of the following enterovirus serotypes (CVB 1, 2, 3, 4, 5, and 6), and induce efficient antibody response but the protection is specific for those viruses which are included in the vaccine, meaning that protection by neutralizing antibodies is serotype specific (Hyoty, col. 8, para. 3).
Thus, the state of the art recognized that it would be highly unpredictable that a generic CVB composition would induce neutralizing antibodies against all strains of CVB, as encompassed by the instant claims. The minimal structure which the skilled artisan would consider predictive of the function of eliciting a neutralizing antibody response would be structural proteins (or nucleic acids encoding and capable of expressing such structural proteins), of the specific CVB serotype that is to be neutralized. One of skill in the art would neither expect nor predict the appropriate functioning of the compositions as broadly as currently claimed.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Stone and Hyoty, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to make and use functional CVB compositions with the requisite intended use of inducing viral neutralizing antibody titer 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 compositions are functional, commensurate in scope with the claimed invention.
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Therefore, the specification does not provide sufficient guidance to allow one skilled in the art to practice the claimed invention on the full scope with a reasonable expectation of success and without undue experimentation. In the absence of such guidance and evidence of working examples, the specification fails to provide an enabling disclosure commensurate in scope with the claim.
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 1-2, 8-10, 13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Stone et al., (Sci. Adv. 2020; 6:33aaz2433, published 5/6/2020, on IDS).
The claimed invention encompasses a composition comprising coxsackievirus B (CVB) of from two to five serotypes, wherein the CVB is in the form of inactivated viral particles (IVP), wherein the composition comprises two or more of: a) CVB1 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP; b) CVB2 in an amount of from 1.0 x 107 IVP to 3.0 x 107 IVP; c) CVB3 in an amount of from 1.0 x 108 IVP to 3.0 x 108 IVP; d) CVB4 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP; and e) CVB5 in an amount of from 4.0 x 107 IVP to 8.0 x 107 IVP, in a volume of 100 µL, wherein the composition does not include CVB6 (claim 1).
The Prior Art
Stone teaches that Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis, as well as hypothesized to be a causal factor in type 1 diabetes (Abstract). Stone further teaches that vaccines against CVBs were not currently available at the time of its publication (2020), and describes the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes, which induces strong neutralizing antibody responses to the six serotypes in both mice nonhuman primate models, and blocks CVB-induced diabetes in a mouse model (Abstract). Stone’s hexavalent CVB vaccine is based on formalin-inactivated CVB-1-6 viruses, which are inactivated in 0.01% (v/v) formalin for 5 days at 37 °C (p. 1, col. 2, last para.). Thus, Stone’s composition encompasses CVB1-5 IVPs, as required by the instant claims, and wherein the IVP are formalin inactivated, as required by instant claim 16. Stone also discloses that its vaccine was administered to mice interscapularly with 1 µg of each serotype of CVB, in 150 µl of vaccine buffer (M199-0.1% Tween, v/v; Fig. 2; p. 10, col. 2, para. 1), and to rhesus macaques with 5 µg of each CVB serotype in 500 µl (150 µl of vaccine buffer + 50 µl alum adjuvant + 300 µl PBS); p. 10, col. 2, para. 3). Thus, Stone’s vaccine compositions comprise an adjuvant and/or saline, as required by claim 17.
Stone also discloses that its vaccines (1 µg of each serotype of CVB) elicited neutralizing antibody titers that are in the range of 1/8 to 1/64,000 for each of CVB1-6 (Fig. 1H; see also Figs. 2 and 4). Claim 8 and its dependent claims 9-10 and 13, require that the composition, when administered to an individual, induces viral neutralizing antibody titer (VNT) of from 1/8 to 1/64,000 as determined by a VNT assay, is interpreted by the examiner to be an intended use of the composition. Stone teaches that its vaccines (1 µg of each serotype of CVB) elicited neutralizing antibody titers that are in the range of 1/8 to 1/64,000 for each of CVB1-6.
Accordingly, Stone teaches a formalin-inactivated vaccine comprising CVB1-6 serotypes, and use of an adjuvant and/or saline in the vaccine formulation. Additionally, Stone teaches that its CVB compositions elicited neutralizing antibody titers that are in the range of 1/8 to 1/64,000 for each of CVB1-6.
However, Stone does not teach wherein the composition does not include CVB6, or a) CVB1 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP (or from 3.0 x 107 to 4.0 x 107 or specifically 3.3 x 107 IVP); b) CVB2 in an amount of from 1.0 x 107 IVP to 3.0 x 107 IVP (or from 1.0 x 107 to 2.0 x 107 or specifically 1.1 x 107 IVP); c) CVB3 in an amount of from 1.0 x 108 IVP to 3.0 x 108 IVP (or from 1.0 x 108 to 2.0 x 108 or specifically 1.5 x 108 IVP); d) CVB4 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP (or from 3.0 x 107 to 4.0 x 107 or specifically 3.2 x 107 IVP); and e) CVB5 in an amount of from 4.0 x 107 IVP to 8.0 x 107 IVP (or 6.0 x 107 or specifically 6.3 x 107 IVP) in a volume of 100 µl, or the same concentration of IVPs in 500 µl.
It would have been obvious to one of ordinary skill in the art to arrive at the instant claims. Notably, Stone’s compositions and methods describe the composition’s CVB quantities by mass (1 or 5 µgs of each serotype of CVB) rather than IVP particle number, as required by the instant claims. Those are a) CVB1 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP (or from 3.0 x 107 to 4.0 x 107 or specifically 3.3 x 107 IVP); b) CVB2 in an amount of from 1.0 x 107 IVP to 3.0 x 107 IVP (or from 1.0 x 107 to 2.0 x 107 or specifically 1.1 x 107 IVP); c) CVB3 in an amount of from 1.0 x 108 IVP to 3.0 x 108 IVP (or from 1.0 x 108 to 2.0 x 108 or specifically 1.5 x 108 IVP); d) CVB4 in an amount of from 2.0 x 107 IVP to 5.0 x 107 IVP (or from 3.0 x 107 to 4.0 x 107 or specifically 3.2 x 107 IVP); and e) CVB5 in an amount of from 4.0 x 107 IVP to 8.0 x 107 IVP (or 6.0 x 107 or specifically 6.3 x 107 IVP) in a volume of 100 µl, or the same concentration of IVPs in 500 µl, as required by claims 1-2, 9-10, and 13. However, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(II). One of ordinary skill in the art would have been motivated to provide sufficient CVB IVPs to elicit an immune response or prevent disease associated with CVB, as disclosed by Stone. Additionally, even if the claimed concentrations of CVB IVPs are substantially higher than the equivalent µg doses disclosed by Stone, the higher amounts would be obvious to one of ordinary skill in the art, because a higher amount could induce a stronger immune response or protective effect, and persons of ordinary skill in the art already consider amount when administering CVB immunogenic compositions, as demonstrated by Stone utilizing 1 µg for mice vaccination and 5 µg for rhesus vaccination. Additionally, concentration of stocks are commonly utilized in the art, and thus would also result in a higher amount of CVB IVPs. Therefore, the required IVP amounts and volumes would have been obvious to one of ordinary skill in the art through routine experimental optimization. See MPEP 2144.05(II).
Regarding the composition not including CVB6, it would have been obvious to one of ordinary skill in the art to omit CVB6 from Stone’s vaccine compositions. Omission of an element and its function is obvious if the function of the element is not desired. See MPEP §2144.04(II)(A). Stone’s compositions are designed to elicit immunity against CVB1-6. It would have been obvious to one of ordinary skill in the art to omit CVB6 from Stone’s compositions if immunity against CVB6 was not desired, such as in the case where a person having ordinary skill in the art desires a composition to elicit immunity against any two or more of CVB1-5, but not necessarily CVB6.
One of ordinary skill in the art would have been motivated to vaccinate against CVB1-5 or CVB1-5 associated diseases. There would be a reasonable expectation of success because Stone discloses formalin-inactivated CVB compositions that elicited an immune response including neutralizing antibodies, against each of CVB1-5, and prevented CVB-associated disease. Therefore, claims 1-2, 8-10, 13, 16, and 17 were prima facie obvious before the priority date of the instant invention.
Conclusion
No claim is allowed.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671
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