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
Acknowledgement is hereby made of receipt and entry of the communication filed on Aug. 5, 2026. Claims 60-71 are pending and currently examined.
Applicant canceled claims 1-59 and added new claims 60-71 which are directed to a method. Previous rejections of canceled claims are withdrawn.
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 of this title, 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.
(Previous Rejection – Modified and Applied to New Claims) Claims 60-71 are rejected under 35 U.S.C. 103 as being unpatentable over Choo et al. (Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1294-1298, submitted in IDS filed on Nov. 27, 2023) in view of Houghton et al. (US 2009/0258033 A1, published on Oct. 15, 2009, submitted in IDS filed on Nov. 27, 2023) and Simmonds et al. (J Gen Virol. 1993 Nov;74 (Pt 11):2391-2399, submitted in IDS filed on Nov. 27, 2023), and further in view of Alexopoulou (ANNALS OF GASTROENTEROLOGY 2001, 14(4):261-272, submitted in IDS filed on Nov. 27, 2023) and Narahari et al. (Infection, Genetics and Evolution 9 (2009) 643–645, submitted in IDS filed on Nov. 27, 2023).
These claims are directed to a method of inducing an immune response in an individual against genotype 1 hepatitis C virus (HCV), genotype 2 HCV, genotype 3 HCV, genotype 4 HCV, genotype 5 HCV, and genotype 6 HCV, the method comprising: administering to the individual an immunogenic composition comprising: a) an HCV genotype 1 E1/E2 heterodimeric polypeptide; b) an HCV genotype 2 E1/E2 heterodimeric polypeptide; c) an HCV genotype 3 E1/E2 heterodimeric polypeptide; and d) a pharmaceutically acceptable excipient, wherein the composition does not include an HCV E1/E2 heterodimeric polypeptide of any genotype other than HCV genotype 1, HCV genotype 2, and HCV genotype 3, and wherein the composition does not include an HCV E1 polypeptide or an HCV E2 polypeptide.
The specification defines the terms E1 polypeptide, E2 polypeptide and E1/E2 polypeptide as following (see PGPub [0094]):
[0094] In the compositions described below, "E2" refers to an E2 polypeptide uncomplexed with an E1 polypeptide, while "E1/E2" refers to E1 and E2 present together in a heterodimeric polypeptide complex. Similarly, the E1 polypeptide can be present in the composition in a heterodimeric complex with an E2 polypeptide, or can be present in the composition uncomplexed with an E2 polypeptide. In the compositions described below, "E1" refers to an E1 polypeptide uncomplexed with an E2 polypeptide, while "E1/E2" refers to E1 and E2 present together in a heterodimeric polypeptide complex.
Choo teaches that a vaccine to control the spread of HCV that represents a major cause of chronic liver disease is needed. It teaches a study with HCV vaccines comprising glycoproteins E1 and E2, and teaches that the E1 and E2 genes used in the study were from HCV-1, that the E1 (33 kDa) and E2 (72 kDa) proteins were selectively co-purified by successive chromatography, and that the resulting E1/E2 (i.e. E1/E2 heterodimer) was used to immunize chimpanzees. See e.g. para spanning pages 1294 and 1295.
Choo teaches that the five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1; the remaining two vaccinees became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections; and that these results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. See e.g. Abstract.
Choo further teaches that another important issue relates to the observed heterogeneity of HCV; that at least six related, but nonetheless distinct, genotypes have been distinguished from phylogenetic analyses, and at least some of these virus types are composed of more than one subtype; that the primary amino acid sequences of the putative envelope glycoprotein domains differ by up to 50% (at least), suggesting that multivalent vaccines may be required for global protection. See page 1298, left column.
Accordingly, Choo teaches a method for immunizing an individual against HCV infection with an E1/E2 heterodimer vaccine from HCV genotype 1. Choo contemplates on the issue of heterogeneity of HCV types and suggests that multivalent vaccines might be required for global protection.
However, Choo does not explicitly teach a vaccine that comprises E1/E2 polypeptides from HCV genotypes 1, 2 and 3 but not from other genotypes.
Houghton teaches HCV E1E2 compositions comprising E1E2 antigens and adjuvants to be used in stimulating immune response in a vertebrate subject. See e.g. Abstract. It teaches that E1E2 complexes are readily produced recombinantly, either as fusion proteins or by e.g., co-transfecting host cells with constructs encoding for the E1 and E2 polypeptides of interest; co-transfection can be accomplished either in trans or cis, i.e., by using separate vectors or by using a single vector which bears both of the E1 and E2 genes. See e.g. PGPub [0095]. Houghton et al. teaches that it is readily apparent that the E1 and E2 polypeptides of the invention encompass E1 and E2 polypeptides from any of the various HCV strains and isolates including isolates having any of the 6 genotypes of HCV described in Simmonds et al., J. Gen. Viral. (1993) 74:2391-2399 (e.g., strains 1, 2, 3, 4 etc.), as well as newly identified isolates, and subtypes of these isolates, such as HCV1a, HCV1b etc. See PGPub [0060]. Houghton teaches that the E1 or E2 polypeptide included in the invention may include a full-length protein or a polypeptide with the C-terminal membrane anchor sequence removed (i.e. soluble polypeptide). See e.g. PGPub [0057-0058]. Houghton teaches that immunostimulatory nucleic acid molecules, such as CpG oligonucleotides, may be used as adjuvant. See e.g. PGPub [0085] and [0114]. Houghton teaches that an E1E2 complex is preferably injected intramuscularly to a large mammal, such as a human. See [0119]. Houghton teaches that antibody titers can be maintained in a mammal by providing one or more booster injections of the E1E2 polypeptides at 2 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 1 year, or more after the primary injection. See [0120].
Simmonds discloses different genotypes of HCVs, including genotypes 1-6 as well as sub-genotypes. See e.g. Table 2, shown below.
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1012
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Alexopoulou teaches that there are differences in the relative prevalence of genotypes and subtypes in distinct geographic areas; and that 1a, 1b, 2a, 2b and 3a are the most prevalent types in Western Europe and North America; Genotype 1 accounts for 50% of the cases and genotypes 2 and 3 for 20% each; in the United States type 1a is the predominant one; Italy, France, and the Netherlands are predominantly infected by 1b; in southern and eastern Europe type 1b is the most prevalent; in Greece, genotype 1b is responsible for 47% of cases, followed by 3a (22%) and 1a (11%); in central Europe genotypes 2 and 3 are absent and almost all infected individuals have genotype 1; in the Middle East and Central Africa, genotype 4 has the highest prevalence rate and in Southern Africa genotype 5 is the most prevalent; in the Far East 1b, 2a and 2b are the most widely distributed; in South-East Asian countries 1b is the most prevalent with the exception of the Philippines where 1a predominates; Genotype 3 with 9 subtypes (a-i) has been observed in Singapore, Thailand, Bangladesh, and eastern India. See e.g. Section 3.2.
Narahari et al. teaches that HCV genotype distribution in the 2118 Indian patients demonstrated prevalence of HCV3 (3a/3b primarily) in 62% and HCV1 (1a/1b primarily) in 31% patients; the predominance of HCV3 was significant in northern (p = 0.01) and eastern (p = 0.008) regions of India; and HCV types 2, 4, 5, and 6 were detected in 0.05–4.5% of the patient group. See e.g. Abstract.
Therefore, teachings of Alexopoulou and Narahari et al. indicate that there is clear distinct in distribution of HCV genotypes in geographical regions around the globe, providing a motivation and guidance on selecting HCV genotypes to be targeted if a multivalent vaccine is to be developed for population in a specific geographical region.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Choo et al., Houghton et al., Simmonds et al., Alexopoulou and Narahari et al. to produce a vaccine composition comprising E1, E2 or E1/E2 polypeptide from genotypes 1, 2 and 3 of HCV. One would have been motivated to do so to produce a multivalent vaccine with potential protection against infections by these HCV genotypes, particularly a multivalent vaccine for populations in a country where genotypes 1, 2 and 3 are prevalent (e.g. Europe and North America). There is reasonable expectation of success that such E1/E2 complex from the claimed HCV types may be produced and combined, as already being shown in Choo et al. and Houghton et al., and that the combination of E1/E2 polypeptides from different genotypes would provide protection against infection of the respective types.
Additionally, such a combination, or a substitution of one element for another known in the field to have the same function for the same purpose, is evidence that the claimed invention may be found obvious. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06. Therefore, the instant invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
It is noted that the limitation of “inducing an immune response in an individual against genotype 1 hepatitis C virus (HCV), genotype 2 HCV, genotype 3 HCV, genotype 4 HCV, genotype 5 HCV, and genotype 6 HCV” is a preamble. A preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP 2111.02 II.
Here, the body of the claims fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations.
Regarding claim 61, one of skill in the art would have found it obvious to use any subtypes of HCV 1-3 in a combination vaccine targeting a relevant geographic location. The claimed subtypes are disclosed in Simmonds.
Regarding claims 68-69, as long as HCV infects intravenous drug users, there is no reason to deprive this patient group of the benefit of a HCV vaccine.
Response to Applicant’s Arguments
Applicant’s arguments filed on Aug. 5, 2026 are fully considered. Arguments regarding withdrawn rejections are moot. Applicant’s arguments relevant to the current rejection are addressed as follows.
To the 103 rejection, Applicant argues that since none of the cited references teach or suggest a method of inducing an immune response in an individual against genotype 1 hepatitis C virus (HCV), genotype 2 HCV, genotype 3 HCV, genotype 4 HCV, genotype 5 HCV, and genotype 6 HCV, the method comprising administering to the individual an immunogenic composition comprising: a) an HCV genotype 1 E1/E2 heterodimeric polypeptide; b) an HCV genotype 2 E1/E2 heterodimeric polypeptide; c) an HCV genotype 3 E1/E2 heterodimeric polypeptide; and d) a pharmaceutically acceptable excipient, wherein the composition does not include an HCV E1/E2 heterodimeric polypeptide of any genotype other than HCV genotype 1, HCV genotype 2, and HCV genotype 3 and does not include an HCV E1 polypeptide or an HCV E2 polypeptide, a prima facie case of obviousness cannot be established.
Applicant’s arguments are not persuasive as indicated in the rejection body above.
Conclusion
No claims are allowed.
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671
