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 Jun. 17, 2024. Claims 48-59 are pending and currently examined.
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 48-53 and 56 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter.
The claims are directed to an immunogenic composition comprising HCV E1, E2 and/or E1/E2 polypeptides from HCV genotypes 1 and 3 and a pharmaceutically acceptable excipient. Both the HCV E1/E2 polypeptides and a pharmaceutically acceptable excipient read naturally occurring products. Simple combination of the two components does not change the structures and properties of the components, and does not amount to significant more to the naturally occurring products.
Therefore, claims 48-53 and 56 are unpatentable under 35 U.S.C. 101.
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.
Claims 48-59 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 an immunogenic composition comprising a hepatitis C virus (HCV) E1, E2 or E1/E2 polypeptide from HCV genotypes 1 and 3, and a pharmaceutically acceptable excipient, wherein the composition does not include an HCV E1/E2 heterodimeric polypeptide, and E1 polypeptide, or an E2 polypeptide of any genotype other than HCV genotypes 1 and 3.
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 et al. 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 et al. 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 et al. 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 et al. contemplates on the issue of heterogeneity of HCV types and suggests that multivalent vaccines might be required for global protection.
However, Choo et al. does not explicitly teach a vaccine that comprises E1, E2 or E1/E2 polypeptide from HCV genotypes 1 and 3.
Houghton et al. 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 et al. 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 et al. teaches that immunostimulatory nucleic acid molecules, such as CpG oligonucleotides, may be used as adjuvant. See e.g. PGPub [0085] and [0114].
Simmonds et al. discloses different genotypes of HCVs, including genotypes 1 and 3 as well as sub-genotypes. See e.g. Table 2, shown below.
PNG
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528
1012
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Greyscale
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 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 and 3 are prevalent (e.g. India and Greece). 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.
Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 48-59 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 of US patent 6,121,020 in view of Choo et al., Houghton et al., Simmonds et al., Alexopoulou and Narahari et al. cited in the rejection above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass an immunogenic composition comprising an E1 polypeptide and an E2 polypeptide. The differences between the two sets of claims include: (1) the patented claims require specific E1 and E2 polypeptides with membrane spanning regions deleted for secretion while the instant claims are directed to E1 and E2 polypeptides in general (which encompass the E1, E2 polypeptide of the patented claims); and (2) the instant claims require that the immunogenic composition comprises E1/E2 polypeptides from HCV genotypes 1 and 3.
As indicated in the art rejection above, the cited references combined suggest a multivalent vaccine composition comprising E1/E2 polypeptides from HCV genotypes 1 and 3.
For the method claims, this rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Therefore, claims 48-59 of instant application are obvious over claims 1-3 of US patent 6,121,020 in view of Choo et al., Houghton et al., Simmonds et al., Alexopoulou and Narahari et al.
Conclusion
No claims are allowed.
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