DETAILED ACTION
Notice of Pre-AIA or AIA Status
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/21/25 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment filed 10/21/2025 is acknowledged. Claims 28, 29, and 31 are cancelled. Claims 22-24, 26-27, and 30 are under examination on the merits.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in United Kingdom of Great Britain and Northern Ireland on 2/28/2022.
Response to Arguments
Applicant’s argument, see p. 4, filed 10/21/2025, with respect to the previous rejection under 35 U.S.C. §112(a) has been fully considered and are persuasive. The rejection under 35 U.S.C. §112(a) has been withdrawn.
Applicant's arguments filed 10/21/2025 regarding the previous rejection under 35 U.S.C. §103 have been fully considered but they are not persuasive. See response below.
The declaration under 37 CFR § 1.132 filed 10/21/2025 is insufficient to overcome the rejection of claims 22-24, 26-27, and 30 based upon 35 U.S.C. 103(a) and the combined teachings of Glanville, et al. and Lau, et al. (see below) as set forth in the last Office action because: the information provided by Co-Inventor Shaw (herein referred to as “Shaw Declaration”) is acknowledged and has been fully considered by the Examiner but is not persuasive for the reasons listed below.
Applicant traversed the rejection under 35 U.S.C. §103 in the reply filed 10/21/2025, but after careful consideration, the examiner has determined that Applicant’s arguments are unpersuasive.
Applicant presents the following arguments:
In the previous response, Applicants disputed the Examiner’s conclusion and the prima facie case of obviousness by i) pointing out that one of skill in the art would not expect a predictable result by modifying the teaching in Glanville with the teachings in Lau because Glanville discloses that immunization of mice with the VP0 protein from RV-A16 generated cellular immunity that cross-reacted with RV-B14, RV-A1, and RV-A29 and does not provide any teaching that the VP0 protein from RV-A16 can evoke cellular immunity that is cross-reactive with RV-A, RV-B, and RV-C species; and ii) pointed to data in the specification demonstrating that RV-A16 immunization, as disclosed in Glanville, does not induce cross-reactive cellular immunity to strains outside of RV-A species (See p. 54, lines 3-19 of the present spec.).
Glanville et al. first suggested that VP0 may be a putative vaccine candidate, because their study demonstrated that the VP0 sequence from the RV-A16 strain elicited cross-strain reactivity to VP0 sequences from heterotypic RV-A strains and a single RV-B strain in mice. However, the data in the present specification demonstrated that the VP0 sequence used by Glanville et al. did not demonstrate cross-reactivity with RV-C strains. As described in the attached Shaw Declaration, experiments to replicate the work of Glanville et al. confirmed that cellular immunity elicited by RV-A16 VP0 immunization in mice recognized VP0 sequences from RV-A strains (Figure 3 of the PCT filing). Importantly however, Glanville et al. did not determine cross-reactivity with RV-C strains (See para. 7 of the Shaw Declaration). In the replication experiments, RV-A16 immunization did not elicit RV-C strain VP0 reactive immunity, and there is no reason one of skill in the art would reasonably expect that the claim-recited immunogenic compositions would successfully induce cross-reactive immunity by modifying the teaching in Glanville et al. with the teaching in Lau et al.
Furthermore, the Shaw Declaration explains the understanding of those of skill in the art at the time of filing of the application. As stated in paragraph 8 of the Shaw Declaration, there was no direction in the literature at the at the time of filing the present application as to which strains or fragment(s) of strains of RV might generate true cross-strain immunity. In particular, the literature suggested that RV-C04 would not generate cross-strain immunity as the evidence is that single strains of RV do not induce cross-strain reactive immunity (see para. 11 of the Declaration). Thus, the literature teaches away from generating immunogenic compositions that elicits an immune response against RV-A, RV-B and RV-C.
As explained in the Shaw Declaration, the Applicant demonstrated that the sequence in Glanville et al. does not elicit an immune response against RV-A, RV-B and RV-C; thus one of skill in the art cannot assume any peptide from any RV strain will elicit cross-strain immunity. Even though Lau et al. teaches a longer sequence including the claim-recited peptide sequences, this reference does not teach using the disclosed peptide sequences in combination with an adjuvant as a vaccine composition. As the literature teaches away from choosing a peptide from RV-C04 to create an immune composition which elicits cross-strain immunity, this claim-recited characteristic does not necessarily flow from the teaching of the prior art. Therefore, the Applicants are not claiming a new property of an old composition as alleged by the Examiner. Thus, the Examiner has not established a prima facie case of obviousness based on the combination of Lau et al. and Glanville et al., and the rejection under 35 U.S.C§103 should be withdrawn.
The claims are also not obvious in view of the unexpected results provided in the specification. To rebut a prima facie case of obviousness, Applicant may provide evidence of secondary considerations such as unexpected results. As stated in the previous response the Applicant has surprisingly discovered that immunization with RV-C04 VP0 (incorrectly referred to as "RV-C24" in the application as filed), i.e., SEQ ID NOs: 13 and 14, evokes cellular immunity that is cross-reactive with other members of the C species of RVs, and RV- A and RV-B species. The Examiner did not find these arguments persuasive because the claims as pending do not "require its method to elicit an immune response against each RV- A, RV-B and RV-C" and Glanville et al. allegedly indicates that its compositions and methods induce cross-reactive immunity. Applicant disputes the Examiner's conclusion; however, to expedite prosecution, claim 22 is amended to recite that claim-recited immunogenic compositions elicit an immune response against RV-A, RV-B and RV-C.
The Shaw Declaration explains that the studies described in the specification provide a novel approach to predict VP0 sequences with the potential to generate cross strain immunity. When the sequences were produced as recombinant protein and used to immunize mice, only VP0 from RV-C04 generated immunity that recognized strains from the three species of RV (RV-A, RV-B and RV-C). This result was surprising and is the first demonstration of an RV vaccine candidate generating immunity to strains from all 3 species of RV.
As explained above and in the Shaw Declaration, Lau et al. simply discloses three strains of HRV-C that were isolated from nasopharyngeal aspirates of hospitalised pediatric patients (strains EF582385 to EF582387). There is no teaching in Lau et al. of an immunogenic composition comprising the RV-C04 peptide and an adjuvant, as claimed, or any experimental data to suggest that such a composition would induce cross-reactive cellular immunity.
Accordingly, when seeking to produce an immunogenic composition that evokes cellular immunity that is cross-reactive with all species of RV, the skilled person would not have been motivated by the disclosure of Glanville et al. and/or Lau et al. to use the RV-C04 peptide (SEQ ID NO: 14), or a nucleotide sequence encoding the peptide (SEQ ID NO: 13), because there is no evidence in either of these disclosures that these sequences have a cross-reactive effect with all species of RV.
Thus, the amended claims are not obvious in view of the cited references and rejection under 35 U.S.C. §103 should be withdrawn.
Applicant’s arguments are not persuasive:
The Shaw Declaration and Applicant’s remarks are not convincing. The Shaw Declaration demonstrates results when SEQ ID NO: 13 is administered, however, the claimed genus is substantially larger than the scope of immunogen administered in the Shaw Declaration and disclosure (e.g., 80% identity could allow for 65 amino acids to be different). Applicant’s argument is that one of ordinary skill in the art, reading Glanville, would not think that the immunogen would be immunogenic against RV-A, RV-B, and RV-C, based on work Applicant has presented in the Shaw Declaration. However, that is not persuasive to the examiner, because that information was not provided by the prior art at the time of the filing. One of ordinary skill in the art, looking at prior art information, wouldn't have known that immunity against RV-C wouldn't have occurred by Glanville’s method, because that information didn't exist until Applicant tested it. Therefore, there is no teach away by Glanville since they never state that their VP0 peptide wouldn’t or didn’t induce immunity against a RV-C.
In addition, while applicant’s argument focuses on the fact that the peptide that Glanville teaches didn't induce immunity against RV-C (para 7 of dec., panel c) the claims do not require immunity to be achieved against all 3 types of rhinovirus. Rather, the claims require that immune responses against RV-A, RV-B and RV-C are elicited by the VP0 peptide of SEQ ID NO: 13 or a polynucleotide of SEQ ID NO 14 and the Shaw Declaration shows at paragraph 7, panel C that an immune response was elicited against at least one of the RV-C’s (RV-C07 pool).
Therefore, applicants have confirmed that the VP0 protein of Glanville inherently elicits an immune response against RV-A, RV-B and RV-C.
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In summary, the declaration and arguments are not convincing. As stated above, applicant reduced to practice administering SEQ ID NO: 13 to mice, and tested it for immune response activation against RV-A, -B, and -C, which was achieved. However, the claims are also drawn to a composition comprising peptides that have 80% identity to SEQ ID NO: 13 or nucleic acids, which is much broader in scope than what was reduced to practice. As established above, the unexpected results espoused by applicants are not interpreted to be unexpected based on Applicant’s data. The deficiency of Glanville is that it doesn’t teach a peptide within the claimed sequence parameters. Therefore, the argument made in the Shaw Declaration and remarks is not commensurate in scope with the data presented therein. One of ordinary skill in the art would arrive at the claimed invention based on the combined teachings of Glanville and Lau.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Rejections Removed
The previous objections and rejections were removed due to Applicant’s amendment:
Rejection under 35 U.S.C. §112(a): claim 30.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
(Previous Rejection Maintained, Claims 28 and 29 removed) Claims 22-24, 26-27, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Glanville, et al. (PLoS Pathog. 2013;9(9):e1003669. doi: 10.1371/journal.ppat.1003669. Epub 2013 Sep 26. PMID: 24086140; hereinafter referred to as “Glanville”) in view of Lau, et al. (J Clin Microbiol. 2007 Nov;45(11):3655-64. doi: 10.1128/JCM.01254-07. Epub 2007 Sep 5. PMID: 17804649; hereinafter referred to as “Lau”). The previous rejection of Claims 28 and 29 is withdrawn due to cancellation of the claims.
The claimed invention encompasses an immunogenic composition comprising an isolated human rhinovirus peptide, or an isolated polynucleotide encoding the peptide, wherein the peptide comprises an amino acid sequence as set out in SEQ ID NO: 13, or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 13, and/or encoded by the nucleotide sequence as set out in SEQ ID NO: 14, or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 14, and wherein the immunogenic composition further comprises an adjuvant, and wherein the immunogenic composition elicits an immune response against RV-A, RV-B, and RV-C, as recited in claim 22. In a specific embodiment, the polynucleotide comprises a nucleic acid sequence encoding the peptide, as recited in claim 23. In another embodiment, the nucleic acid is DNA or RNA, as recited in claim 24. In another embodiment, the immunogenic composition is a vaccine, as recited in claim 26.
In another embodiment, the claimed invention encompasses a method of eliciting an immune response in a subject against a rhinovirus infection, the method comprising administering, to a subject in need thereof, a therapeutically effective amount of an immunogenic composition comprising an isolated human rhinovirus peptide, or an isolated polynucleotide encoding the peptide, wherein the peptide comprises an amino acid sequence as set out in SEQ ID NO: 13, or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 13, and/or wherein the peptide is encoded by the nucleotide sequence as set out in SEQ ID NO: 14, or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 14, and wherein the immunogenic composition further comprises an adjuvant, as recited in claim 27. In another embodiment of the claimed method, the immunogenic composition (i) elicits an immune response against common colds and/or virus-induced wheezing illnesses, and/or (ii) reduces exacerbations of asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), cystic fibrosis and/or chronic fibrosing lung disease, as recited in claim 30.
The Prior Art
Glanville teaches that human rhinovirus infections are the principle cause of common colds and elicit asthma and COPD exacerbations (Abstract). Glanville further teaches that rhinovirus vaccination is complicated due to the existence of about 150 strains, and determined that the VP0 capsid (VP4+VP2) region exhibit high homology across rhinovirus strains (Fig S1; Abstract). Glanville demonstrated that immunization with recombinant VP0, along with adjuvant, induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses, and that immunization facilitated heterosubtypic neutralizing antibodies and memory T cells (Figs. 1-5). Vaccination also led to faster viral clearance an animal model (Fig. 6).
However, Glanville does not teach an isolated human rhinovirus peptide that comprises an amino acid sequence as set out in SEQ ID NO: 13 or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 13, and/or wherein the peptide is encoded by the nucleotide sequence as set out in SEQ ID NO: 14, or a variant or fragment thereof having at least 80% sequence identity to SEQ ID NO: 14.
Lau teaches isolation and characterization of human rhinoviruses from nasopharyngeal aspirates (NPAs) of hospitalized pediatric patients (Lau, generally; Page 3656). Lau also specifically teaches extraction of viral RNA from the NPAs and subsequent complete genome sequencing and analysis (Page 3656), which uncovered a new genetic clade, HRV-C, that is phylogenetically distinct from the previously two known HRV species, HRV-A and HRV-B (Lau, generally; Abstract). Three strains of HRV-C that were identified were deposited in the Genbank database under accession numbers, including EF582385, which was also described as HRV-C 024 (Page 3656). Notably, SEQ ID NO: 14 of the instant application is identical to a portion of Genbank EF582385 (Appendix A), which encodes a protein identical to SEQ ID NO: 13. Febrile wheezing and asthma were the most common presentation of these HRV-C infections (Table 1; Abstract). While Lau do not teach the combination of an isolated HRV-C protein, that is identical to SEQ ID NO: 13, with an adjuvant, this protein would inherently possess the ability to elicit an immune response against RV-A, RV-B and RV-C.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Glanville to incorporate an isolated human rhinovirus peptide (SEQ ID NO: 13) or polynucleotide (SEQ ID NO: 14) encoding the peptide taught by Lau. One of ordinary skill in the art would have been motivated to vaccinate against human rhinovirus group C since, much like RV-A and RV-B, it is a public health concern, based on the reporting by Lau. As taught by Glanville, the VP0 capsid region exhibits high homology across rhinovirus strains, and immunization with the VP0 capsid region and an adjuvant is an effective vaccination strategy for eliciting cross-serotype immune responses. Additionally, Lau demonstrates that HRV-C Genbank EF582385, a portion of which is identical to SEQ ID NO: 14 and encodes the polypeptide SEQ ID NO: 13, is a potentially impactful pathogen because the virus specimen was obtained from a hospitalized child. Therefore, Claims 22-24 and 26-31 were prima facie obvious to one of ordinary skill in the art before the priority date of the instant invention.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671