DETAILED ACTION
Final Rejection
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group I: claims 1-43 in the reply filed on 05/29/2025 is acknowledged.
Applicant has cancelled Group II claims 44-45, Group III claims 46-47, Group IV claim 48 and Group V claim 49 in response to restriction/election office action dated 04/01/2025.
Requirement for an election of species is withdrawn for (i) an aluminum hydroxide adjuvant, and (ii) aluminum hydroxide gel.
Status of Claims
3. Claims 1-3, 5-6, 8-23, 31-39, and 43 amended claim listing filed on 03/09/2026 are pending and under examination.
4. Claims 4, 7, 24-30, and 40-42 are cancelled by the applicant.
Information Disclosure Statement
5. The information disclosure statements (IDS) submitted on 01/05/2023, 07/12/2023, 05/29/2025, and 03/09/2026 are acknowledged. The submission is in-compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
6. This application is a U.S. National Phase under 35 U.S.C. 371 of International Patent Application No. PCT/US2020/057361, filed October 26, 2020, which claims priority to U.S. Provisional Appl. 62/926,357 filed October 25, 2019, and U.S. Provisional Appl. No. 62/993,563 filed March 23, 2020. Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f). Copies of the certified copies of the priority documents have been received in this National Stage application from the International Bureau (PCT Rule 17.2(a)).
Claim Interpretation
7. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The instant claim 2 is interpreted to recite an alternative limitation “a composition” or “a vaccine” comprising a virus-like particle (VLP) which comprises a capsid protein and an envelope protein derived from Chikungunya virus (CHIKV). The added claim limitation on the function to induce neutralizing antobody is interpreted to be met by the composition when the composition comprises the claimed elements of the VLP. The functional limitations are recited as: (i) induces a neutralizing antibody response against CHIKV in a subject within 7 days after administration of a single dose of the composition or vaccine to the subject and/or (ii) induces a neutralizing antibody response against CHIKV which persists for at least 28 days, at least 6 months, at least 1 year, or at least 2 years after a single dose is administered to the subject.
Statements in the preamble reciting the purpose or intended use of the claimed invention are evaluated as to whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art.
If it does impart a structural or manipulative difference, the recitation serves to limit the claim.
A prior art structure which is capable of performing the purpose or intended use meets the claim. See MPEP 2111.02.
Withdrawn Rejection of Claims
8. Withdrawn rejection of claims 1-3, 5-6, 8-9, 13-16, 22-23, 32 and 36-39 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Ella et al 2013 (US20130022631A1 published 01/24/2013) in view of applicant’s amendment of claims.
9. Withdrawn rejection of claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Wizel et al 2019 (WO2019016756A1 published 01/24/2019) in view of applicant’s amendment of claims.
Claim Rejections - 35 USC § 103 (modified)
10. 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.
11. Claims 1-3, 5-6, 8-9, 13-16, 22-23, 32 and 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Ella et al 2013 (US20130022631A1 published 01/24/2013), and further in view of Livengood et al 2017 (WO2017172643A1, 10/05/2017, cited on IDS filed on 03/09/2026), Kam et al 2012 (Journal of Virology vol 86 (23), p. 13005–13015), Khan et al 2012 (Virus Research, 167 (2012) 236– 246) and Chua et al 2016 (PLoS Negl Trop Dis 10(8): e0004960).
Claim 1: Ella et al 2013 (US20130022631A1) is in the art and discloses a composition or vaccine, comprising: (a) a virus-like particle (VLP) which comprises a capsid protein and an envelope protein derived from Chikungunya virus (CHIKV), the vaccine for Chikungunya virus is made by expressing the entire structural polyprotein consisting of the Capsid, E3, E2 (envelope protein), 6K polypeptide and E1 proteins that is cloned as a single polypeptide with a potential to assemble into a Virus Like Particle (VLP) in eukaryotic host cells (See, para [0047], claim 17); (b) an adjuvant aluminum hydroxide (See, para [0065], para [0049], [0064], [0065] and claim 20); (c) sucrose (See, para [0065], claims 9-10); and (e) a carrier which can be buffer or water, immunogen is in a lyophilized form and after reconstitution in a pharmaceutically acceptable buffer or water is suitable for administration (See, claim 19, para [0046], [0065]).
Ella et al 2013 do not teach instant amended claim 1 limitation (d) a buffer and/or pH modifier that is one or more of potassium phosphate monobasic, potassium phosphate dibasic, and sodium citrate dehydrate.
Livengood et al 2017 (WO2017172643A1) teaches limitation (d) a buffer and/or pH modifier that is potassium phosphate (see, claim 26, 29-30, 48, and 51). It would have been obvious to potassium phosphate monobasic or potassium phosphate dibasic based on the pH buffering requirements.
Claims 2 and 36-39: Ella et al 2013 (US20130022631A1) is in the art and discloses a composition or vaccine, comprising a virus-like particle (VLP) which comprises a capsid protein and an envelope protein derived from Chikungunya virus (CHIKV), the vaccine for Chikungunya virus is made by expressing the entire structural polyprotein consisting of the Capsid, E3, E2 (envelope protein), 6K polypeptide and E1 proteins that is cloned as a single polypeptide with a potential to assemble into a Virus Like Particle (VLP) in eukaryotic host cells. The VLPs are highly immunogenic as they mimic the native virus particle in structure. The VLPs contain multiple copies of the antigenic proteins in their assembled structure. (See, para [0047], claim 17). The added limitation of instant claim 2, wherein the composition or vaccine (i) induces a neutralizing antibody response against CHIKV in a subject within 7 days after administration of a single dose of the composition or vaccine to the subject reads on Example 11 para [0062] Determination of the Immunogenicity of the Virus, polyclonal antibodies were raised in rabbit by injecting 100 μg of the purified Chikungunya virus CHK/03/06 isolate intradermally / subcutaneously / intramuscularly. Injection of a single dose of virus purified from BHK21 cells gave an ELISA titer of ˜6400, and a titer of >80 by virus neutralization assay compared to normal rabbit serum of ˜4. A neutralizing antibody titer of the anti-serum obtained by immunization with the above particles in a stable formulation, as measured by in vitro neutralization assay offers protective immunization in animals (See, para [0034]). The prior art Ella et al 2013 (US20130022631A1) meets all the components of the VLP of chikungunya virus as per claim 2 and provided the evidence of capability of functionality by showing induction of neutralizing antibody response against the chikungunya virus (See, Example 11 para [0062]). The prior art thus suggests that the composition or vaccine of the instant claim 2 meets and anticipates the added limitation (ii) induces a neutralizing antibody response against CHIKV which persists for at least 28 days, at least 6 months, at least 1 year, or at least 2 years after a single dose is administered to the subject.
Claim 3: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2, further comprising an adjuvant in claims 19-20 and 22. Ella et al 2013 teaches the vaccine formulation comprises a pharmaceutically accepted buffer such as phosphate or phosphate-citrate buffer in the pH range 6.4-7.5 (See, para [0028] [0046], [0052], [0064]- [0065] and claims 9-10). A vaccine may optionally contain preservative(s) (See, para [0046]). Ella et al 2013 therefore has option to not comprise preservative or antibiotic in the vaccine composition.
Claim 5: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 4, wherein the adjuvant is aluminum hydroxide gel reads on the adjuvant is an aluminum hydroxide adjuvant in para [0049], [0064], [0065] and claim 20.
Claim 6: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2, wherein the capsid protein is a CHIKV C protein (See, para [0047].
Ella et al 2013 (US20130022631A1) disclosed the composition or vaccine, wherein the envelope protein is a CHIKV protein selected from the group consisting of E3, E2, 6K, E1, and any combination thereof (See, para [0047].
Claim 8: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2, wherein the VLP comprises CHIKV envelope proteins E2 and E1 (See, para [0047].
Claim 9: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2, wherein the VLP comprises CHIKV C, E2, and E1 proteins (See, para [0047].
Claim 13: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2 which is a suspension suitable for intramuscular injection (See, para [0028], [0035], [0046], [0062], [0064]).
Claims 14-16: Ella et al 2013 (US20130022631A1) disclosed the added limitation the composition or vaccine, wherein the single dose of the composition or vaccine comprises claimed VLP quantity in μg by disclosing dose from 1 μg to about 200 μg (See para [0064]), 100 μg (para [0062]), and 1 to 1000 μg preferably 5 to 500 μg and more preferably 10 to 100 μg for vaccination per dose (See, claim 21). The recited doses read on the claimed Chikungunya virus VLP composition or vaccine doses.
Claim 22: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 2, wherein the single dose of the composition or vaccine comprises a volume of about 0.5 mL to 2 mL (See, para [0013], [0035], [0049]).
Claims 23 and 32: Ella et al 2013 (US20130022631A1) disclosed the added limitation of the composition or vaccine of claim 22, wherein the single dose of the composition or vaccine comprises a volume of about 0.5 mL to 1 mL (See, para [0013], [0035], [0049]).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior teachings of Ella et al 2013 with additional teachings of Livengood et al 2017 as recited supra to arrive at the inventions of claims 1-3, 5-6, 8-9, 13-16, 22-23, 32 and 36-39. The motivation would be to develop a stable and efficacious protective VLP vaccine for commercial success in view of teachings of Kam et al 2012 that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response (See, abstract); and Khan et al 2012 teaches that the envelope protein E1 and E2 being the major immunodominant structural proteins with crucial role in virus attachment and entry, can prove to be potential vaccine candidates (See, abstract); and Chua et al 2016 teaching the antigenic variation of East/Central/South African and Asian chikungunya virus Genotypes (See, abstract, entire article). One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied and as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1-3, 5-6, 8-9, 13-16, 22-23, 32 and 36-39. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
12. Claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39 are rejected under 35 U.S.C. 103 as being unpatentable over Wizel et al 2019 (WO2019016756A1 published 01/24/2019), and further in view of Livengood et al 2017 (WO2017172643A1, 10/05/2017), Kam et al 2012 (Journal of Virology vol 86 (23), p. 13005–13015), Khan et al 2012 (Virus Research, 167 (2012) 236– 246) and Chua et al 2016 (PLoS Negl Trop Dis 10(8): e0004960).
Claim 1: Wizel et al 2019 (WO2019016756A1) is in the art and discloses a composition or vaccine comprising: (a) a virus-like particle (VLP) which comprises a capsid protein and an envelope protein derived from Chikungunya virus (CHIKV) taught as VLPs comprising capsid and envelope proteins C-E3-E2-6k-E1 (See, p.55-56, example 3); (b) an adjuvant aluminum hydroxide adjuvant- to evaluate the effect of adjuvant on CHIKV VLP immunogenicity, immunizations were performed with either no adjuvant, or with an adjuvant selected from aluminum hydroxide (alum) (See, p.56-57, Example 4, lines 30-32, p. 48, lines 19-27, 29-31); (c) a sugar taught as stabilizers (in the vaccine composition art sugars are used as stabilizers) (See, p.28, line 2); (d) a buffer and/or pH modifier taught as pH adjusters (See, p.28, line 2), phosphate buffered saline (p.58, line 19, Example 5); and (e) a carrier is disclosed as pharmaceutically or physiologically acceptable carrier such as isotonic saline, isotonic salt, solution or other formulations that will be apparent to those skilled in the art (See, p.28, line 12-13).
Wizel et al 2019 do not teach instant amended claim 1 limitation (d) a buffer and/or pH modifier that is one or more of potassium phosphate monobasic, potassium phosphate dibasic, and sodium citrate dehydrate.
Livengood et al 2017 (WO2017172643A1) teaches limitation (d) a buffer and/or pH modifier that is potassium phosphate (see, claim 26, 29-30, 48, and 51). It would have been obvious to potassium phosphate monobasic or potassium phosphate dibasic based on the pH buffering requirements.
Claims 2, and 36-39: Wizel et al 2019 (WO2019016756A1) is in the art and discloses a composition or vaccine comprising a Chikungunya virus virus-like particle (CHICKV VLP) production using an expression plasmid, the codon-optimized nucleic acid encoding CHIKV C-E3-E2-6k-E1 in HEK293 cells and purification of the VLPs comprising capsid and envelope proteins C-E3-E2-6k-E1 (See, p.55, example 3). Immunization of mice with VLP-CHIKV by intramuscular route, immunizations were performed with either no adjuvant, or with an adjuvant selected from aluminum hydroxide (alum), AS01 E or AS04. AS01 E is an Adjuvant System containing MPL, QS-21 and liposome. CHIKV VLPs induced neutralizing antibody (nAb) titers above the detection threshold, immunogenicity of the 0.1 μg dose of CHIKV VLPs was enhanced by co-administration of adjuvants (Alum, AS01 or AS04), durability of the immune response induced by VLP-CHICK immunization in mice, one or two dose immunizations with VLP-CHICKV (See, p.58, lines 10-19, table 2), sera collected before immunization and at day 21, (See, p. 56-60, Example 4: Immunogenicity of VLP-CHIKV, Examples 5-6), induces a neutralizing antibody response against CHIKV which persists for at least 28 days, at least 6 months, at least 1 year, or at least 2 years after a single dose is administered to the subject by disclosing figure 12 showing strong immune response at week 9 for the single dose vaccine with AS01e adjuvant (See, p.59, line 12-17, Figure 12).
The combined teachings of prior art Wizel et al 2019 and Livengood et al 2017 meets all the components of the VLP of chikungunya virus as per claim 2 and provided the evidence of capability of functionality by showing induction of neutralizing antibody response against the chikungunya virus (See, p.55, example 3, p. 56-60, Example 4: Immunogenicity of VLP-CHIKV, Examples 5-6, See, p.58, lines 10-19, table 2, p.59, line 12-17, Figure 12). The prior art thus suggests that the composition or vaccine of the instant claim 2 meets and anticipates the added limitation (ii) induces a neutralizing antibody response against CHIKV which persists for at least 28 days, at least 6 months, at least 1 year, or at least 2 years after a single dose is administered to the subject.
See, MPEP 2111.04: The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps").
Claims 3: Wizel et al 2019 (WO2019016756A1) discloses the added limitation of claim 3, further comprising an adjuvant that may be used in the context of the compositions of the invention include inorganic adjuvants e.g. inorganic metal salts such as aluminum phosphate or aluminum hydroxide, gel-like precipitates of aluminum hydroxide (alum) (See, p. 48, lines 19-27, 29-31).
Claims 5 and 35: Wizel et al 2019 (WO2019016756A1) discloses the added limitations of claims 5 and 35, wherein the adjuvant is aluminum hydroxide gel, alhydrogel (See, p. 48, lines 19-27, 29-31);
the composition or vaccine which induces a neutralizing antibody response against CHIKV in a subject within 7 days after administration of the single dose of the composition or vaccine to the subject (See, p. 56-60, Example 4: Immunogenicity of VLP-CHIKV, Examples 5-6).
Claims 6, and 8: Wizel et al 2019 (WO2019016756A1) discloses the added limitation of claims 6-8, wherein the capsid protein is a CHIKV C protein, VLPs comprising capsid and envelope proteins is a CHICKV protein C-E3-E2-6k-E1 (See, p.1 lines 23-24, See, p.55, example 3; A diagram of the resulting pMAX-CHIKV plasmid is shown in Figure 6).
Claim 12: Wizel et al 2019 (WO2019016756A1) discloses the added limitation of claim 12, wherein the capsid and envelope proteins are derived from CHIKV strain 37997, neutralizing Abs elicited to VLPs based on the West-African CHIKV strain (#37997) (See, p. 8, lines 17-21; p.10 line 9).
Claim 13: Wizel et al 2019 (WO2019016756A1) teaches the added limitation of claim 13 which is a suspension suitable for intramuscular injection by disclosing evaluation of the immunogenicity of CHIKV viral like particles (VLPs) expressing the same CHIKV structural polyproteins. C57BL/6 (B6) mice (10/group) were immunized intramuscularly at days 0 and 28 (See, p. 56, example 4, lines 27-30).
Claims 22-23 and 32. Wizel et al 2019 (WO2019016756A1) teaches the added limitation of claims 22-23 and 32 on volume of doses in mL, wherein the single dose of the composition or vaccine comprises a volume of about 0.5 mL to 2 mL (instant claim 22); wherein the single dose of the composition or vaccine comprises a volume of about 0.5 mL to 1 mL (instant claim 23); wherein the single dose of the composition or vaccine is a volume of about 0.8 mL (instant claim 32) by disclosing generally a human dose will be in a volume of between 0.1 ml and 2ml, such as 0.5 ml and 2 ml. Thus, the composition described herein can be formulated in a volume of, for example 0.1, 0.25, 0.5, 1.0, 1.5 or 2.0 ml human dose per individual or combined immunogenic components. One of skill in the art may adjust these doses, depending on the route of administration and the therapeutic or vaccine application for which the recombinant vector is employed. (See, p. 29, lines 31-34).
Claims 33-34: Wizel et al 2019 (WO2019016756A1) teaches the added limitation of claims 33-34, wherein the VLP induces antibodies against homologous or heterologous strains of CHIKV; and wherein the VLP induces antibodies against one or more CHIKV lineages selected from the group consisting of East/Central/South African (ECSA), West African and Asian by disclosing the results indicate that neutralizing antibody responses elicited by the West African CHIKV strain have activity against the La Reunion strain (ECSA genotype) and the Caribbean strain (Asian genotype) (See, p. 56-58, example 4, specifically p. 58 Immunogenicity results lines 4-7).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior teachings of Wizel et al 2019 with additional teachings of Livengood et al 2017 as recited supra to arrive at the inventions of claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39. The motivation would be to develop a stable and efficacious protective VLP vaccine for commercial success in view of teachings of Kam et al 2012 that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response (See, abstract); and Khan et al 2012 teaches that the envelope protein E1 and E2 being the major immunodominant structural proteins with crucial role in virus attachment and entry, can prove to be potential vaccine candidates (See, abstract); and Chua et al 2016 teaching the antigenic variation of East/Central/South African and Asian chikungunya virus Genotypes (See, abstract, entire article). One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied and as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
13. Claims 1-3, 5-6, 8-23, and 32-39 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Wizel et al 2019 (WO2019016756A1 published 01/24/2019) Livengood et al 2017 (WO2017172643A1, 10/05/2017), Kam et al 2012 (Journal of Virology vol 86 (23), p. 13005–13015), Khan et al 2012 (Virus Research, 167 (2012) 236– 246) and Chua et al 2016 (PLoS Negl Trop Dis 10(8): e0004960) as applied to claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39 above and further in view of Ella et al 2013 (US20130022631A1 published 01/24/2013), and Chang et al 2014 (Lancet 2014; 384: 2046–52).
The disclosures of Ella et al 2013 (US20130022631A1) as applied to claims 1-3, 5-6, 8-9, 13-16, 22-23, 32 and 36-39 as recited above, and the disclosures of Wizel et al 2019 (WO2019016756A1) as applied to claims 1-3, 5-6, 8, 12-13, 22-23, and 32-39 as recited supra renders obvious those claims, and the disclosures are incorporated here by reference in its entirety.
Claims 9-11: The composition or vaccine of claim 2 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Chang et al 2014 is in the art and teaches the added limitations of instant claims 9-11 by disclosing chikungunya virus VLP vaccine consists of chikungunya VLPs composed of the E1, E2, and capsid proteins from the chikungunya virus strain 37997. VLPs were produced by transfection of human embryonic kidney VRC293 cells with a DNA plasmid encoding the structural genes of the chikungunya virus. The VRC293 cells are a suspension-adapted serum-free cell line derived from HEK-293 cells (See, p.2048, col 2). The VLPs are produced by a DNA plasmid construct encoding chikungunya virus C, E2, and E1 proteins and thus the three proteins C, E2, and E1 would be expected to be at least 95% of the VLP proteins in the composition and also does not comprise CHIKV E3 and/or 6K.
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior teachings of Ella et al 2013, Livengood et al 2017and Wizel et al 2019 to incorporate the teachings of Chang et al 2014 on chikungunya virus strain 37997 to arrive at the inventions of claims 9-11. The motivation would be to develop an efficacious protective vaccine in view of teachings of Kam et al 2012 that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response (See, abstract); and Khan et al 2012 teaches that the envelope protein E1 and E2 being the major immunodominant structural proteins with crucial role in virus attachment and entry, can prove to be potential vaccine candidates (See, abstract); and Chua et al 2016 teaching the antigenic variation of East/Central/South African and Asian chikungunya virus
Genotypes (See, abstract, entire article). One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied and as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 9-11. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, G).
Claims 14-21: The composition or vaccine of claim 2 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Claims 14-17: Ella et al 2013 teaches the added limitations on amount of μg doses of the VLPs of claims 14-17 by disclosing the VLP virus antigen(s) are used in the range of 1 to 1000 μg preferably 5 to 500 μg and more preferably 10 to 100 μg for vaccination per dose. (See, claims 21 and 15, 17, 19-21); the potency of the vaccine formulation has been tested in doses ranging from 1 μg upto 200 μg of the antigen (para [0028]).
Claims 15-17: Chang et al 2014 teaches the added limitations on amount of μg doses of the VLPs of claims 15-17 by disclosing the chikungunya virus VLP vaccine was administered intramuscularly (deltoid muscle) by needle and syringe at 10 μg (in 0·25 mL), 20 μg (in 0·5 mL), and 40 μg (in 1 mL).
Claims 18-21: Wizel et al 2019 teaches adjuvants that may be used in the context of the compositions of the VLP invention include inorganic adjuvants (e.g. inorganic metal salts such as aluminum phosphate or aluminum hydroxide), gel-like precipitates of aluminum hydroxide (alum); AIP04; alhydrogel (See, p. 48, lines 29-31). The mice were immunized intramuscularly at days 0 and 28 (dO, d28) with 10, 1 or 0.1 μg VLP of Chikungunya virus (See, Example 4).
Ella et al 2013 teaches partially the added limitations of claims 18-21 on μg doses of the VLPs by disclosing a pharmaceutical composition according to claim 19 wherein the virus antigen(s) are used in the range of 1 to 1000 μg preferably 5 to 500 μg and more preferably 10 to 100 μg for vaccination per dose (See, claim 21).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior teachings of Ella et al 2013 and Wizel et al 2019 as applied to claim 2 to incorporate the additional teachings of Ella et al 2013 and Wizel et al 2019 on the VLP doses and adjuvants aluminum hydroxide (alum), alhydrogel including the teachings of Chang et al 2014 on doses of VLP quantity of CHICKV to arrive at the inventions of claims 14-21. The motivation would be to optimize the VLP quantity and evaluate with adjuvants aluminum hydroxide or alhydrogel per dose for optimal immune response for commercial success. One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied and as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 14-21. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, G).
Furthermore, according to section 2144.05 of the MPEP, 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). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages”).
Claims 24-29: The composition or vaccine of claim 2 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Claims 24-29: Ella et al 2013 (US20130022631A1) teaches the added limitations of claims 24-29 by disclosing sugars such as sucrose, maltose, trehalose, lactose as a stabilizing agent (See, para [0028], claims 9-10, para [0065]).
Claims 27-29: The composition or vaccine of claim 2 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Ella et al 2013 teaches the added limitation of claims 27-29 by disclosing the vaccine formulation comprises a pharmaceutically accepted buffer such as phosphate or phosphate-citrate buffer in the pH range 6.4-7.5 (See, para [0028] [0046], [0052], [0064]- [0065] and claims 9-10). A vaccine may optionally contain preservative(s) (See, para [0046]).
Wizel et al 2019 teaches that optionally, a vaccine or immunogenic composition of the invention may be formulated to contain other components, including, e.g., adjuvants, stabilizers, pH adjusters, preservatives and the like (See, p.28, lines 1-3).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to further modify the combined prior teachings of Ella et al 2013 and Wizel et al 2019 as applied to claim 2 to incorporate the teachings additional teachings on sugar/sucrose as a stabilizer for the VLP and buffer and pH modifier for stability and as a carrier to arrive at the invention of claims 24-29. The motivation would be stabilize the VLP vaccine composition during transportation and keeping integrity of structure and quality of the VLPs and exclude the preservatives and antibiotics to prevent undesired reactivity of sensitive subjects and for commercial success. One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the applied prior art teachings. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 24-29. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, G).
14. Claims 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Ella et al 2013 (US20130022631A1 published 01/24/2013), Wizel et al 2019 (WO2019016756A1 published 01/24/2019) and Chang et al 2014 (Lancet 2014; 384: 2046–52) as applied to claims 2-4 above, and further in view of Chang et al 2014 (Lancet 2014; 384: 2046–52), Petrosky et al 2015 (MMWR Morb Mortal Wkly Rep. 2015, 27;64(11):300-4), HogenEsch et al 2018 (npj Vaccines (2018) 51, p. 1-11) and Kim et al 2012 (PLoS ONE 7(4): e35893).
Claims 30-31: The composition or vaccine of claim 4 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Chang et al 2014 teaches the VLP vaccine composition of CHIKIV, the vaccine was administered intramuscularly (deltoid muscle) by needle and syringe at 10 μg (in 0·25 mL), 20 μg (in 0·5 mL), and 40 μg (in 1 mL). Based on preclinical data, the VLP chikungunya virus vaccine. Thus, the human dose in ml is typically 0.5 ml a (See, Effect of adjuvant dose, p. 2048, col 2, para 3).
Ella et al 2013 teaches the potency of the Chikungunya virus VLP vaccine formulation has been tested in doses ranging from 1 μg upto 200 μg (See, para [0028]).
Petrosky et al 2015 is in the virology and VLP vaccine art and teaches two to nine valent HPV VLP licensed vaccine compositions comprising 500 µg aluminum hydroxide adjuvant (See, p. 301, table 1, abstract).
HogenEsch et al 2018 is in the virology and VLP vaccine art and reviewed optimizing the utilization of aluminum adjuvants in vaccines. HogenEsch et al 2018 teaches that the amount of aluminum adjuvant in vaccines is typically expressed as the concentration of elemental aluminum per dose. One mg of Al3+ corresponds with 2.2 mg AH and about 4.5 mg AP. The maximum amount of aluminum per dose in human vaccines in the United States is 0.85 mg (850 µg) Al3+ if determined by assay and 1.14 mg if determined by calculations (US Code of Federal Regulations, 21CFR610.15). The amount may be increased to 1.25 mg (1125 µg) if supported by data that this dose is safe and necessary to induce the desired effect. Licensed human vaccines typically contain between 0.2 and 0.8 mg (200 to 800 µg ) of Al3+ (p.6, Table 1). Because of the large adsorptive capacity of aluminum adjuvants, only a small dose is necessary to adsorb vaccine antigens. However, a larger dose than required for maximal adsorption is sometimes necessary to achieve an optimal immune response. Preclinical studies should be conducted to determine the minimum dose of aluminum adjuvant that induces a maximal immune response. For preclinical studies in rodents, the vaccine formulation intended for human use should not be diluted with saline or buffer as this can affect the adsorption of vaccine antigens. Instead, a fraction of the human dose, typically one-fifth or one-tenth (0.1– 0.05 ml) for mice, should be used (See, p. 4-4, col 2 para 2, p.5 table 1).
Kim et al 2012 is in the virology and HPV VLP art and teaches the immunization of mice with hHPV16 VLP- and cHPV16 VLP-immunization groups each received subcutaneously injections of 1000 ng of hHPV16 VLPs or cHPV16 VLP, in combination with aluminum hydroxide (200 mg per dose) (See, p.9 col 1, section on - mice immunization).
Ella et al 2013 teaches CHICKV VLP vaccine composition and sucrose in the range of 0.5%-10% (2.5 mg - 50 mg per 0.5 ml dose of vaccine) and preferably in the range of 0.5% to 5% (2.5 mg – 25 mg per 0.5 ml dose of vaccine) conferred good stability on the formulation as determined by accelerated stability at 370 C for three weeks (See, para 0065]). Ella et al 2013 additionally teaches a carrier as phosphate buffer, 10 mM to 500 mM pH 6.7 to 7.4 or phosphate-citrate buffer of similar pH and water (See, para 0065], claim 9).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior teachings of Ella et al 2013 and Wizel et al 2019 to incorporate the teachings of Chang et al 2014 on doses of VLP of CHICKV and Petrosky et al 2015, HogenEsch et al 2018 and Kim et al 2012 on quantity of aluminum hydroxide and Ella et al on buffer composition to arrive at the inventions of claims 30-31. The motivation would be to optimize the VLP quantity and aluminum hydroxide adjuvant quantity per dose for optimal immune response and the sucrose concentration/quantity and the buffer composition for optimal stability and for commercial success. One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied and as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 30-31. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, G).
Furthermore, according to section 2144.05 of the MPEP, 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). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages”).
15. Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Ella et al 2013 (US20130022631A1 published 01/24/2013), Wizel et al 2019 (WO2019016756A1 published 01/24/2019) and Chang et al 2014 (Lancet 2014; 384: 2046–52) as applied to claims 2 above, and further in view of Merck and Company Inc 2011 (Merck and Company Inc, 2011 Package insert for GARDASIL).
Claim 43: The composition or vaccine of claim 2 is taught by combined teachings of Ella et al 2013 and Wizel et al 2019 the prior arts as recited supra.
Merck and Company 2011 disclosures are in the virology and VLP vaccine art and teaches a pre-filled syringe comprising the single dose of the composition or vaccine HPV VLP vaccine (See, p. 3, item 3).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior teachings of Ella et al 2013 and Wizel et al 2019 as applied to claim 2 to incorporate the teachings of Merck and Company 2011 to the vaccine composition of claim 2 to obtain the prefilled syringe to arrive at the invention of claim 43. The motivation would be for logistic and convenience of the healthcare provider and commercial success. One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings Merck and Company 2011 and it is routine in the vaccines directed to the human subjects. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 43. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, G).
Response to Arguments
16. Applicant’s arguments with respect to claims 1-3, 5-6, 8-23, 31-39, and 43 amended claim listing filed on 03/09/2026 have been considered but are moot because the new ground of rejection does not rely only on reference applied in the prior rejection of record for all teaching or matter specifically challenged in the argument. A new reference Livengood et al 2017 (WO2017172643A1, 10/05/2017) that was recited in the IDS is applied in this office action.
Applicant’s arguments:
Applicant argued the rejection under 35 U.S.C. 102 and 35 U.S.C. 103 are improper because applicant opinion that the referenced prior art did not anticipate or render obvious the claims.
Applicant argued secondary evidence regarding superior immunostimulatory effect of VLP vaccine composition and stability to the VLP vaccine composition.
In Response:
Prior rejection (09/09/2025) under 35 USC 102 is withdrawn.
Prior rejection (09/09/2025) under 35 USC 103 is modified to render obvious the amended claims as shown in the office action.
Applicant’s argument regarding secondary evidence of superior immunostimulatory effect of VLP vaccine composition and stability to the vaccine / VLP vaccine composition is considered. The prior art applied in the instant modified obviousness rejection rendered obvious the instant composition claims and therefore the applied prior arts are reasonably expected to achieve the stability and immunostimulatory effect of the claimed composition as instantly claimed superior by the applicant.
Applicant's arguments filed are considered in entirety and fully, but they are not persuasive.
Conclusion
17. No claim is allowed.
18. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner , Art Unit 1600
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