DETAILED ACTION
Non-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 species in the reply filed on 10/21/2025 is acknowledged.
Applicant elected following species:
SEQ ID NO: 1, as recited in claims 1 and 40-41.
SEQ ID NO: 100, as recited in claim 45; and
SEQ ID NO: 10 and SEQ ID NO: 16, as recited in claims 42-43.
Applicant did not indicate the claims on which the elected species of SEQ ID NO: 1, 10, 16 and 100 read on.
The examiner interpreted the elected species read on the pending claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47.
Priority
3. This application is the national stage entry of Appl. No. PCT/IB2020/054864, filed on May 21, 2020, which claims priority to U.S. Provisional Patent Application No. 62/851,546, filed on May 22, 2019.
Status of Claims
4. Claims 1-7,12-13,17,27-28,34,40-43 and 45-47 filed on 10/21/2025 are pending.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 07/06/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
6. The PCT ISA written opinion indicated a reference/prior art “Anonymous: "MVA.HTI and ChAdOx1.HTI B/ES/18/20 SUMMARY NOTIFICATION INFORMATION FORMAT FOR THE RELEASE OF GENETICALLY MODIFIED ORGANISMS OTHER THAN HIGHER PLANTS IN ACCORDANCE WITH ARTICLE 11 OF DIRECTIVE 2001/18/EC", 17 August 2018 (2018-08-17), pages 1-43, XP055715545, Retrieved from the Internet: URL:https://gmoinfo.jrc.ec.europa.eu/bsnifs-gmo/B-ES-18-20.pdf [retrieved on 2020-07-16]” reads on the claimed inventions (anticipation).
The examiner was unable to retrieve the above reference using the weblink cited by the PCT and via request for reference delivery from internal resource USPTO STIC.
The examiner was unable to locate the reference on the considered IDS filed on 07/06/2022.
Applicant may provide the above recited reference if available.
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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 1 and dependent claims are interpreted to be directed to a method of treating or preventing a human immunodeficiency virus (HIV) infection or a disease associated with an HIV infection in a subject in need thereof, comprising administering to the subject sequential one or more doses of a DNA vector and a first viral vector (MVA or ChAd) and a second viral vector encoding a immunogenic polypeptide recited in the SEQ ID NO: 1, 10, 16 and 100 or fusion of the tow polypeptides or the polypeptides encoded by a sequence having at least 90% or 95% identity. Any two polypeptides (e.g. SEQ ID NO: 10 and 16) can be constructed as a fusion polypeptide that is fused by an amino acid linker Alanine. The subjects are also claimed to have developed HIV-1 caused immunosuppression exhibited by a disease as AIDS, ARC or HIV opportunistic disease due to severe immunosuppression prior to the immunogen administration as a treatment.
Specification
8. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
On page 17 of the specification filed on 11/18/2021 has an embedded hyperlink: http://blast.ncbi.nlm.nih.gov/blast.cgi, January 2012.
Claim Rejections - 35 USC § 112
9. Claims 1-7,12-13,17,27-28,34,40-43 and 45-47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a HIV disease or infection (e.g. HIV-1), does not reasonably provide enablement for a method of preventing a HIV infection (e.g. HIV-1). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use or use the invention commensurate in scope with these claims. The specification does not enable one of the ordinary skills to prevent a HIV infection in a subject as claimed in instant claim 1.
The instant specification (See, para [0041]0 defined the terms "prevent”, "preventing," and "prevention", as used herein, refer to inhibiting the inception or decreasing the occurrence of a disease in an animal. Prevention may be complete (e.g., the total absence of pathological cells in a subject). The prevention may also be partial, such that for example the occurrence of pathological cells in a subject is less than that which would have occurred without the present invention. Prevention also refers to reduced susceptibility to a clinical condition.
A susceptible cell in a subject can be infected with an HIV virus (e.g. HIV-1 virus) and the cell may not display pathology or the HIV genome may be integrated in the cellular genome as a “proviral genome” that can result rescue of a HIV virus under adverse or immunosuppression or reduced therapeutic effect of an anti-HIV drug or anti-HIV immune response.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). These factors include, but are not limited to:
The breadth of the claims: The claims are broad with regard to the claim limitation “prevention” of HIV is broad. The claims in the current form are directed to protect against both known types of HIV: HIV-1 and HIV-2, and their all subtypes whereas the claimed polypeptide for immunization/administration are derived from HIV-1.
(B) The nature of the invention: The invention is directed to an unsolved problem in the field of HIV. The HIV virus genome although is RNA, it has a DNA intermediate and LTR sequences at the 5’ and 3’ end; and the DNA sequence integrates in the host cell chromosomal DNA and remains dormant. The HIV infectious virus is generated when the antiretroviral therapy is discontinued or when the immunogen immune response wanes. Therefore, with the current state of knowledge in the HIV prevention art it is not possible to prevent HIV infection to a susceptible cell. HIV is highly variable and exist in HIV-1 and HIV-2 types and many different subtypes.
(C) The state of the prior art: There are many prior arts available in the HIV vaccination or immunization and treatment and it is ever changing field due to variant HIV-1 and HIV-2 strains.
(D) The level of one of ordinary skill: PhD scientist with many years of experience skills is required to work in the field of “HIV infection prevention”
(E) The level of predictability in the art: Because of the highly evolutionary genetic nature of HIV there is a high level of unpredictability in the HIV prevention art.
(F) The amount of direction provided by the inventor: The inventor did not provide a working example demonstrating prevention of the HIV (e.g. HIV-1, HIV-2 and different subtypes of HIV- 1 and HIV-2) infection (See, Franchini et al 1989, and see, instant specification para [0036]).
(G) The existence of working examples: The inventor did not provide a working example demonstrating prevention of the HIV (e.g. HIV-1, HIV-2 and different subtypes of HIV- 1 and HIV-2) infection (See, Franchini et al 1989, and see, instant specification para [0036]) infection by treatment using the claimed HIV-1 polypeptides. Extraordinary and undue experimental burden on the ordinary skills. Applicant has provided examples to induce immune response in mice against the HIV-1 polypeptides.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure: HIV is broad genus and included types HIV-1 and HIV-2 and their many different subtypes (See, e.g. HIV-1, HIV-2 and different subtypes of HIV- 1 and HIV-2) infection (See, Franchini et al 1989, and see, instant specification para [0036]). The inventor did not provide a working example demonstrating prevention of the HIV infection by treatment using the claimed HIV-1 polypeptides. The applicant has put undue and most likely an unachievable extraordinary experimental burden is placed on the ordinary skills.
At least for the reasons discussed above, an unreasonable amount of additional research is required to obtain repeatable demonstration of “prevention” of HIV (e.g. HIV-1, HIV-2 and their subtypes) infection in the subjects. Thus, it would require undue experimentation for one skilled in the art to completely enable the claimed methods of prevention of HIV infection. The instant specification does not provide complete enablement for the instant claims because there is not a single working example that demonstrate the HIV prevention invention and there is no data that demonstrate an achieved complete prevention of HIV (e.g. HIV-1, HIV-2 and their subtypes) infection in a subject by the claimed methods in instant claims 1-7,12-13,17,27-28,34,40-43 and 45-47.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
10. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7,12-13,17,27-28,34,40-43 and 45-47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims 1-7,12-13,17,27-28,34,40-43 and 45-47 contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The independent claim 1 and dependent claims 2-7,12-13,17,27-28,34,40-43 and 45-47 are directed to: a method of treating or preventing a human immunodeficiency virus (HIV) infection or a disease associated with an HIV infection in a subject in need thereof, comprising: sequentially administering to the subject a DNA vector, MVA, ChAd viral vectors encoding the claimed polypeptides (SEQ ID NOs: 1, 10, 16 and 100) that are derived from HIV-1.
The term HIV could potentially encompass human immunodeficiency virus type 1, 2, or both 1 and 2. However, HIV-1 and -2 are genotypically and phenotypically distinct (See, Franchini et al 1989). These viruses display different pathogenicity and geographical distributions. Moreover, these viruses only display 52%, 54%, and 35% amino acid sequence identity in Gag, Pol, and Env, respectively.
The instant specification (See, para [0036]) defined the term "human immunodeficiency virus" or "HIV", as used herein, refers to human immunodeficiency viruses generically and includes HIV type 1 ("HIV-1"), HIV type 2 ("HIV-2") or other HIV viruses, including, for example, the HIV-1, HIV-2, emerging HIV and other HIV subtypes and HIV variants, such as widely dispersed or geographically isolated variants and simian immunodeficiency virus ("SIV"). For example, an ancestral viral gene sequence can be determined for the env and gag genes of HIV-1, such as for HIV-1 subtypes A, B, C, D, E, F, G, H, J, and K, and intersubtype recombinants such as AG, AGI, and for groups M, N, O or for HIV-2 viruses or HIV-2 subtypes A or B. HIV-1, HIV-2 and SIV include, but are not limited to, extracellular virus particles and the forms of the viruses associated with their respective infected cells. Perusal of the specification suggests the invention is directed toward methods of treating HIV-1 infection in a subject comprising administering relatively conserved HIV-1 polypeptides referred as HTI immunogens (See, instant specification para [0048] Table 1 for the polypeptides derived from HIV-1).
The specification including drawings does not provide immunization examples and data obtained from polypeptides derived from HIV-2 or different subtypes of HIV-1 and HIV-2 (for HIV-1 and HIV-2 subtypes, see instant specification para [0036]). The specification including drawings does not provide challenge and protection studies data even against HIV-1.
The claims in the current form are directed to protect against all types and subtypes of HIV whereas the claimed polypeptide for immunization/administration are derived from HIV-1.
The breadth of the claims: The claims are broad with regard to the claim limitation “prevention” of HIV is broad. The claims in the current form are directed to protect against both known types of HIV: HIV-1 and HIV-2, and their all subtypes whereas the claimed polypeptide for immunization/administration are derived from HIV-1.
The existence of working examples: The inventor did not provide a working example demonstrating prevention of the HIV (e.g. HIV-1, HIV-2 and different subtypes of HIV- 1 and HIV-2) infection (See, Franchini et al 1989, and see, instant specification para [0036]) infection by treatment using the claimed HIV-1 polypeptides. Extraordinary and undue experimental burden on the ordinary skills. Applicant has provided examples to induce immune response in mice against the HIV-1 polypeptides.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: HIV is broad genus and includes types HIV-1 and HIV-2 and their many different subtypes (See, e.g. HIV-1, HIV-2 and different subtypes of HIV- 1 and HIV-2) infection (See, Franchini et al 1989, and see, instant specification para [0036]). The inventor did not provide a working example demonstrating prevention of the HIV infection by treatment using the claimed HIV-1 polypeptides. The applicant has put undue and most likely an unachievable extraordinary experimental burden is placed on the ordinary skills.
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004).
To provide adequate written description and evidence of possession of a claimed genus, especially where the genus, especially where the genus requires a difficult to achieve and thus unpredictable function (e.g. “HIV type 1 (HIV-1) polypeptide immunogen expected to function as inducer of protection against HIV type 2 (HIV-2) and all subtypes of HIV-1 and HIV-2”). In this case the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof for HIV-2 polypeptide and polypeptides from different HIV-1 and HIV-2 subtypes. In this case, the only factor present in the claims is a genus “HIV-1 polypeptides” and a function of inducing immune response to protect against HIV type 2 (HIV-2) and all subtypes of HIV-1 and HIV-2 is unpredictable.
See, EliLily, 119 F.3 at 1568, 43 USPQ2d at 1406. The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the detailed chemical structure polypeptides of HIV type 2 (HIV-2) and all subtypes of HIV-1 and HIV-2. Given that the specification has only described the function of a component (HIV-1 polypeptide), the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112(a). The applicant/inventor needs to show that they have truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, the applicant/inventor has only a research plan, leaving it to others to explore and figure out the unknown contours of the claimed genus." AbbVie Deutsch/and GmbH & Co. v. Janssen Biotech, 759 F.3d 1285, 1300 (Fed. Cir. 2014). "In other words, the test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad, 598 F.3d at 1351.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated: “A written description of an invention involving a chemical genus, like a description of a chemical species requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or sub-combinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” The MPEP 2163 does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitute a sufficient number of representatives, the Courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Further, regarding the broad claims directed to HIV the applicant is referred to MPEP 2163 and the University of Rochester v. GD. Searle & Co. Inc. federal court decision that prohibits “reach through claims” as failing to provide possession of the invention at the time of filing.
Appropriate correction is required to limit the claims to HIV-1.
Claim Rejections - 35 USC § 103
11. 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.
12. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013) and further in view of Aelix Therapeutics 2017 (ClinicalTrials.gov ID: NCT03204617, First posted 07/02/2017),
Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1, 01/14/2016).
Claims 1-4, 7, 12, 34, 40-41: Brander et al 2018 (US9988425B2) is in the art and teaches a method of treating or preventing a human immunodeficiency virus (HIV) infection or a disease associated with an HIV infection in a subject in need thereof comprising administration to a subject a nucleic acid molecule encoding an immunogenic polypeptide (DNA vector e.g. non-viral expression vector pcDNA3.1 plasmid vector), viral expression vectors e.g. Modified Vaccinia Ankara virus (MVA), adenoviruses (See, col 14, lines 16-67, col 15 lines 1-67, col 16 lines 1-9, and claims 1-30, see entire prior art). Brander et al 2018 (US9988425B2) teaches SEQ ID NO: 1 (Db) that has 100% sequence identity with SEQ ID NO: 1 (Qy) of instant claim 1 as recited below:
Query Match 100.0%; Score 403; Length 78;
Best Local Similarity 100.0%;
Matches 78; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELK 60
Qy 61 SLYNTVATLYCVHQKIEV 78
||||||||||||||||||
Db 61 SLYNTVATLYCVHQKIEV 78
Brander et al 2018 (US9988425B2) teaches the present invention relates to the immunogenic polypeptide, the nucleic acid, the expression cassette, the expression vector, the virus or the cell of the third aspect, or the composition vaccine for use in the prevention or treatment of an HIV infection or a disease associated with an HIV infection (See, col 3 lines 58-67). The expression “sequential administration”, as used herein, means that the administration is not simultaneous, but a first administration is performed, followed by one or more successive administrations for prevention or treatment (See, col 8 lines 4-7, and lines 17-30). Suitable dosages of the nucleic acids and expression vectors can be determined by those of skill in the art, for example by measuring the immune response of a subject, such as a laboratory animal, using conventional immunological techniques, and adjusting the dosages as appropriate. Such techniques for measuring the immune response of the subject include but are not limited to, chromium release assays, tetramer binding assays, IFN ELISPOT assays, IL-2 ELISPOT assays, intracellular cytokine assays, and other immunological detection assays (See, col 19 lines 66-67, col 20 lines 1-28, see entire prior art). Brander et al 2018 (US9988425B2) teaches priming by DNA vector expressing the polypeptide (reads on SEQ ID NO: 1) followed by MVA boost expressing the polypeptide (reads on SEQ ID NO: 1), (See, Fig. 8 (a) and associated legends in col 3).
Brander et al 2018 (US9988425B2) does not teach administration to the subject of a second viral vector encoding the immunogenic polypeptide and separation in time frame of primary and booster dosage immunization in months.
Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617) teaches a clinical trial on “Safety and Immunogenicity Study of DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1-positive Patients (AELIX-002)”. The AELIX-002 study aims to evaluate the safety and the immunogenicity of an heterologous prime-boost regimen with DNA.HTI, MVA.HTI and ChAdOx1.HTI in early diagnosed and treated HIV-1 positive individuals, males and females,18-60 years of age. The administration of the HIV HTI polypeptide encoding DNA vectors or MVA and ChAd virus vectors was done as follow: Biological: DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM). Biological: At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM). Drug: Placebo. (See, page 1-3 of attached PDF printout of ClinicalTrial ID: NCT03204617 by Aelix Therapeutics 2017, see entire prior art).
Ondondo et al 2016 is in the art and teaches preclinical immunogenicity of T-cell vaccine expressing novel immunogens tHIVconsvX, vectored by DNA, chimpanzee adenovirus (ChAd), and poxvirus modified vaccinia virus Ankara (MVA), a combination highly immunogenic in humans. The tHIVconsvX immunogens combine the three leading strategies for elicitation of effective CD8(+) T cells: use of regions of HIV-1 proteins functionally conserved across all M group viruses (to make HIV-1 escape costly on viral fitness), inclusion of bivalent complementary mosaic immunogens (to maximize global epitope matching and breadth of responses, and block common escape paths), and inclusion of epitopes known to be associated with low viral load in infected untreated people (to induce field-proven protective responses). tHIVconsvX was highly immunogenic in two strains of mice. Furthermore, the magnitude and breadth of CD8(+) T-cell responses to tHIVconsvX-derived peptides in treatment-naive HIV-1(+) patients significantly correlated with high CD4(+) T-cell count and low viral load. Overall, the tHIVconsvX design, combining the mosaic and conserved-region approaches, provides an indisputably better coverage of global HIV-1 variants than previous T-cell vaccines. These immunogens delivered in a highly immunogenic framework of adenovirus prime and MVA boost are ready for clinical development (See, abstract, see entire prior art).
Brander et al 2018 (US9988425B2) teaches discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV-1 CTL epitope Gag77–85 (See, abstract, see entire prior art).
Mothe et al 2015 is in the art and teaches a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals that aimed to direct the T cell response to the most vulnerable sites of HIV-1 and led to discovery of a human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques (See, abstract, entire article).
Boggiano et al 2005 teaches discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV-1 CTL epitope Gag77–85 suggesting significance of conserved Gag epitopes and high immunogenicity required for protection through HIV-1 specific cytotoxic T cell response (See, abstract, entire article).
Almeida et al 2012 teaches T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4+ T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4+ T-cell epitopes in vaccines and led to discovery of broad and cross-clade CD4⁺ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides (See, abstract, entire article).
Geleziunas 2021 teaches a method of treating an HIV infection in a human comprising the step of administering to the human in need thereof a pharmaceutically effective amount of an HIV vaccine (See, claims 2, 8 and 10, para [0624]), live vector vaccines encoding HIV-1 antigens, such as those selected from the group of gag, pol, env, nef, rev, tat, vif, vpr, vpu, and antigenic proteins, variants and fusion proteins thereof (See, para [0625], [0626], [1471], see entire prior art).
Claim 5: Brander et al 2018 (US9988425B2) teaches the added limitation of instant claim 5, wherein the DNA vector comprises a human cytomegalovirus (CMV) promoter and/or a bovine growth hormone (BGH) polyadenylation site (See, col 15 lines 15-26, see entire prior art).
Claim 6: As recited supra, Brander et al 2018 (US9988425B2) (See, col 14, lines 16-67, col 15 lines 1-67, col 16 lines 1-9, and claims 1-30), and Ondondo et al 2016 (See, abstract, entire article) teaches the added limitation of instant claim 6, wherein the first and/or second viral vector is a Modified Vaccinia Ankara (MVA) virus vector and/or a chimpanzee adenovirus (ChAd) vector.
Claim 13. Brander et al 2018 (US9988425B2) teaches the added limitation of instant claim 13, wherein the DNA vector is administered at a dose of from about 0.1 mg to about 20 mg by disclosing immunogenicity of the HIVACAT T cell immunogen was evaluated in 6-8 weeks old female C57BL/6 mice. 20 μg and 5 μg of DNA was delivered intramuscularly by electroporation using the Inovio system in the left and right quadriceps (20 μg/50 μl per dose, 25 μl per site) at week 0 and 4 (See, Brander et al 2018 (US9988425B2) col 30 Example 2).
Claim 17: Brander et al 2018 (US9988425B2) teaches the added limitation of instant claim 17, wherein the first and/or second viral vector is administered at a dose of from about 1x107 plaque forming units (pfu) to about 1x109 pfu by disclosing mice immunizations 106 pfu of MVA-HIVACAT by intramuscular injection (See, Col 3 FIG 8 a) associated legends; col 34 Example 4 section of In-Vivo Immunogenicity in C57BL/6 Mice). Optimizing the claimed dose of the viral vector from about 1x107 plaque forming units (pfu) to about 1x109 pfu is routine laboratory practice to for obtaining the optimal immune response and protection and is within the skill of the ordinary. See, MPEP 2144.05.
Claims 27-28: Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617) teaches a clinical trial on “Safety and Immunogenicity Study of DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1-positive Patients (AELIX-002)”. The AELIX-002 study aims to evaluate the safety and the immunogenicity of a heterologous prime-boost regimen with DNA.HTI, MVA.HTI and ChAdOx1.HTI in early diagnosed and treated HIV-1 positive individuals, males and females,18-60 years of age. The administration of the HIV HTI polypeptide encoding DNA vectors or MVA and ChAd virus vectors was done as follow: Biological: DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM). Biological: At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM). Drug: Placebo. (See, page 1-3 of attached PDF printout of ClinicalTrial ID: NCT03204617 by Aelix Therapeutics 2017).
Mothe et al 2015 is in the art and teaches added limitations of instant claims 27-28 regarding administering of the immunogen doses separated by a period of from about 2 months to about 24 months (claim 27) or by a period of from about 3 months to about 18 months (claim 28) by disclosing prime and booster does of HTI immunogen in mice (See, Figure 4 legends and figure, see entire article) that teaches separation of primary dose and the booster dose by 3 weeks. Brander et al 2018 (US9988425B2) added limitations of instant claims 27-28 regarding administering of the immunogen or the vaccine doses separated by a period of 3 weeks (See, Example 4 lines 50-59 in col 34 Example 4 section of In-Vivo Immunogenicity in C57BL/6 Mice).
Claims 42-43: Brander et al 2018 (US9988425B2) teaches added limitations of instant claims 42-43), wherein at least two of the sequences SEQ ID NO: 10 and SEQ ID NO: 16 are adjoined by an amino acid linker (instant claim 42); wherein the amino acid linker is a single, dual, or triple alanine linker, and wherein the linker results in the formation of an AAA sequence in the junction region between adjoining sequences, and/or wherein the sequence of each of SEQ ID NO: 10 and SEQ ID NO: 16 is 11-85 amino acids in length (instant claim 43).
Brander et al 2018 (US9988425B2) teaches SEQ ID NO: 10 (Db) that has 100% identity with instant claim 42 SEQ ID NO: 10 (Qy) as recited below:
Query Match 100.0%; Score 316; Length 55;
Best Local Similarity 100.0%;
Matches 55; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LRWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKL 55
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 LRWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKL 55
Brander et al 2018 (US9988425B2) teaches SEQ ID NO: 16 (Db) that has 100% identity with instant claim 42 SEQ ID NO: 16 (Qy) as recited below:
Query Match 100.0%; Score 69; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AWLEAQEEEEVGF 13
|||||||||||||
Db 1 AWLEAQEEEEVGF 13
Brander et al 2018 (US9988425B2) teaches a linker wherein (the polynucleotide sequences encoding the polypeptide encode amino acid Alanine) the polypeptides are joined by a single, dual, or triple alanine amino acid linker, wherein the linker results in the formation of an AAA sequence in the junction region between adjoining sequences, wherein the sequence of each of the polypeptide is 11-85 amino acids in length (See, claim 1 (xvi), claim 3, claim 6, claim 18, col 5 lines 14-25).
Claim 45: Brander et al 2018 (US9988425B2) teaches added limitation of instant claim 45, wherein the immunogenic polypeptide is encoded by a nucleic acid comprising the SEQ ID NO:100 by disclosing 100% identical SEQ ID NO:100 (Db) as recited below:
Query Match 100.0%; Score 1587; Length 1587;
Best Local Similarity 100.0%;
Matches 1587; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAGAAGATCCGGCTGCGGCCAGGCGGAAAGAAGAAGTACAAGCTGAAGCACATCGTCTGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAGAAGATCCGGCTGCGGCCAGGCGGAAAGAAGAAGTACAAGCTGAAGCACATCGTCTGG 60
Qy 61 GCCTCGAGGGAGCTGGAGCGGTTCGCGGTGAACCCGGGACTTCTGGAGACGTCGGAGGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GCCTCGAGGGAGCTGGAGCGGTTCGCGGTGAACCCGGGACTTCTGGAGACGTCGGAGGGG 120
Qy 121 TGCAGGCAGATCCTCGGCCAGCTGCAGCCCTCTCTGCAAACGGGGTCTGAGGAGCTGAAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TGCAGGCAGATCCTCGGCCAGCTGCAGCCCTCTCTGCAAACGGGGTCTGAGGAGCTGAAG 180
Qy 181 AGCCTGTACAACACGGTGGCGACCCTCTACTGCGTCCACCAGAAGATCGAGGTGGCAGCG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AGCCTGTACAACACGGTGGCGACCCTCTACTGCGTCCACCAGAAGATCGAGGTGGCAGCG 240
Qy 241 GCCAAGGCGTTCTCGCCGGAGGTCATCCCCATGTTCTCGGCGCTGGCAGCTGCCGGACAC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GCCAAGGCGTTCTCGCCGGAGGTCATCCCCATGTTCTCGGCGCTGGCAGCTGCCGGACAC 300
Qy 301 CAGGCCGCGATGCAGATGCTGAAGGAGGCCGCTGCGATCGCACCGGGCCAGATGAGGGAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CAGGCCGCGATGCAGATGCTGAAGGAGGCCGCTGCGATCGCACCGGGCCAGATGAGGGAG 360
Qy 361 CCACGCGGTTCCGACATCGCGGGAACCACCTCGACGCTCCAGGAGCAGATCGGATGGATG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CCACGCGGTTCCGACATCGCGGGAACCACCTCGACGCTCCAGGAGCAGATCGGATGGATG 420
Qy 421 ACGAACAACCCGCCAATCCCGGTCGGGGAGATCTACAAGCGGTGGATCATCCTCGGGCTG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ACGAACAACCCGCCAATCCCGGTCGGGGAGATCTACAAGCGGTGGATCATCCTCGGGCTG 480
Qy 481 AACAAGATCGTCCGGATGTACAGCCCGACGTCGATCGCTGCGGCATACGTTGACCGGTTC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AACAAGATCGTCCGGATGTACAGCCCGACGTCGATCGCTGCGGCATACGTTGACCGGTTC 540
Qy 541 TACAAGACCCTGAGGGCCGAGCAGGCAGCGGCCTGCCAGGGGGTCGGTGGACCAGGGCAC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TACAAGACCCTGAGGGCCGAGCAGGCAGCGGCCTGCCAGGGGGTCGGTGGACCAGGGCAC 600
Qy 601 AAGGCCCGAGTGCTCGCGGCCGCATGCACGGAGCGGCAGGCGAACTTCCTGGGGAAGATC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AAGGCCCGAGTGCTCGCGGCCGCATGCACGGAGCGGCAGGCGAACTTCCTGGGGAAGATC 660
Qy 661 TGGCCGTCGCACAAGGGCCGACCGGGAAACTTCCTCCAGTCTCGCGCAGCGGCTAAGATG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TGGCCGTCGCACAAGGGCCGACCGGGAAACTTCCTCCAGTCTCGCGCAGCGGCTAAGATG 720
Qy 721 ATCGGAGGCATCGGAGGCTTCATCAAAGTCCGTCAGTACGACCAGATCCTCATCGAGATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 ATCGGAGGCATCGGAGGCTTCATCAAAGTCCGTCAGTACGACCAGATCCTCATCGAGATC 780
Qy 781 TGCGGGCACAAGGCGATCGGAACCGTGCTCGTCGGCCCAACGCCCGTGAACATCATCGGC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 TGCGGGCACAAGGCGATCGGAACCGTGCTCGTCGGCCCAACGCCCGTGAACATCATCGGC 840
Qy 841 CGCAACCTGTTAACGCAGATCGGCTGCACCCTCAACTTCGCCGCACTAGTGGAGATCTGC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CGCAACCTGTTAACGCAGATCGGCTGCACCCTCAACTTCGCCGCACTAGTGGAGATCTGC 900
Qy 901 ACGGAGATGGAGAAGGAGGGCAAGATATCGAAGATCGCGGCAGCTCTGAGGTGGGGCTTC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 ACGGAGATGGAGAAGGAGGGCAAGATATCGAAGATCGCGGCAGCTCTGAGGTGGGGCTTC 960
Qy 961 ACCACGCCGGACAAGAAGCACCAGAAGGAGCCGCCATTCCTGTGGATGGGATACGAGCTG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ACCACGCCGGACAAGAAGCACCAGAAGGAGCCGCCATTCCTGTGGATGGGATACGAGCTG 1020
Qy 1021 CACCCGGACAAGTGGACCGTGCAGCCCATCGTCCTGCCGGAGAAGGACTCGTGGACGGTG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 CACCCGGACAAGTGGACCGTGCAGCCCATCGTCCTGCCGGAGAAGGACTCGTGGACGGTG 1080
Qy 1081 AACGACATCCAGAAGCTCGTGGGGAAGCTGGCGGCAGCCATCCTCAAGGAGCCCGTCCAC 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 AACGACATCCAGAAGCTCGTGGGGAAGCTGGCGGCAGCCATCCTCAAGGAGCCCGTCCAC 1140
Qy 1141 GGGGTGTACTACGACCCCTCTAAGGACCTGATCGCGGAGATCCAGAAGCAGGGGCAGGGT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GGGGTGTACTACGACCCCTCTAAGGACCTGATCGCGGAGATCCAGAAGCAGGGGCAGGGT 1200
Qy 1201 CAGTGGACCTACCAGATCTACGCAGCAGCAACCAAGGAGCTGCAGAAGCAGATCACGAAG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 CAGTGGACCTACCAGATCTACGCAGCAGCAACCAAGGAGCTGCAGAAGCAGATCACGAAG 1260
Qy 1261 ATCCAGAACTTCCGCGTATACTACCGCGACTCGCGGGACCCCCTGTGGAAGGGCCCTGCG 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 ATCCAGAACTTCCGCGTATACTACCGCGACTCGCGGGACCCCCTGTGGAAGGGCCCTGCG 1320
Qy 1321 AAGCTTCTCTGGGCAGCCGCGAAGATCATCCGGGACTACGGCAAGCAGATGGCGGGCGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 AAGCTTCTCTGGGCAGCCGCGAAGATCATCCGGGACTACGGCAAGCAGATGGCGGGCGAC 1380
Qy 1381 GACTGCGTGGCCGCAGCGGTGAAGCACCATATGTACATCTCGAAGAAGGCGAAGGGCTGG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 GACTGCGTGGCCGCAGCGGTGAAGCACCATATGTACATCTCGAAGAAGGCGAAGGGCTGG 1440
Qy 1441 TTCTACAGACACCACTACGAGTCCACCCACCCCAGGGCAGCTGCGGTGACGAAGCTGACG 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TTCTACAGACACCACTACGAGTCCACCCACCCCAGGGCAGCTGCGGTGACGAAGCTGACG 1500
Qy 1501 GAGGACCGGTGGAACAAGCCCCAGAAGACGAAGGGTCACCGGGCGGCTGCATGGCTGGAG 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GAGGACCGGTGGAACAAGCCCCAGAAGACGAAGGGTCACCGGGCGGCTGCATGGCTGGAG 1560
Qy 1561 GCTCAGGAGGAGGAGGAGGTGGGCTTC 1587
|||||||||||||||||||||||||||
Db 1561 GCTCAGGAGGAGGAGGAGGTGGGCTTC 1587
Claim 46: Brander et al 2018 (US9988425B2) teaches added limitation of instant claim 46, wherein the disease associated with an HIV infection is an acquired immune deficiency syndrome (AIDS), AIDS-related complex (ARC), or HIV opportunistic disease (See, col 5 lines 6-13; col 3 lines 58-67).
Claim 47. Brander et al 2018 (US9988425B2) teaches added limitation of instant claim 47, wherein the HIV is HIV type 1 (HIV- 1) (See, col 6 lines 37-51).
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.” See, MPEP 2144.05, 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”).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the prior art teachings of Brander et al 2018 with additional teachings of the prior art by Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016, Mothe et al 2015, Boggiano et al 2005, Almeida et al 2012, and Geleziunas 2021 to arrive at the inventions of claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47. One of the ordinary skills would have been motivated to optimize and develop the claimed method(s) of treating or preventing a human immunodeficiency virus (HIV) infection or a disease associated with an HIV infection in a subject in need thereof, inter alia, comprising sequential administration of DNA vector, and viral vectors, MVA vector and ChAd vector encoding the claimed immunogenic polypeptides or the nucleic acid sequences encoding the broadly reactive conserved polypeptide (as per the HIV-1 HIT polypeptide design and choice) to treat and or prevent HIV disease AIDS or ARC in the subjects and for commercial success of the claimed immunization methods. There would have been a reasonable expectation of success given the applied prior art teachings as recited supra and the knowledge and skills of the ordinary in the art to render the methods of claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 obvious 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 claimed inventions of claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47. 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).
Double Patenting
13. 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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 11, 14-17, 20-26, 28-30 of copending Application No. 19/065036 further in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and co-pending claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of a DNA vector or viral vectors MVA and ChAd expressing the claimed HIV polypeptides. The co-pending claims require antiretroviral therapy in addition to the HIV HTI immunogens administration.
Copending claim 8 SEQ ID NO: 1 has 100% identity to instant claim 1 SEQ ID NO: 1.
Copending claim 11 SEQ ID NO: 99 has 100% identity to instant claim SEQ ID NO: 99.
Copending claim 17 SEQ ID NOs: 100 and 101 has 100% identity to instant claim SEQ ID NOs: 100 and 101.
It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the co-pending claims by incorporating antiretroviral therapy in addition to the HIV HTI immunogens administration for controlling the HIV viremia and restore the immune status of the individual to some extent to obtain a better immune response to the claimed HIV HTI immunogen/vaccine with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the copending claims as compared to the instant claims.
This is a provisional nonstatutory double patenting rejection.
15. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-19, and 21-27 of copending Application No. 17/610,040 further in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437) Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and co-pending claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of a DNA vector or viral vectors MVA and ChAd expressing the claimed HIV polypeptides. The co-pending claims require TLR7 modulating compound in addition to the HIV HTI immunogens administration.
It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the co-pending claims by incorporating TLR7 modulating compound in addition to the HIV HTI immunogens administration for enhancing immune response to the claimed HIV HTI immunogen/vaccine with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the co-pending claims as compared to the instant claims.
This is a provisional nonstatutory double patenting rejection.
16. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. US9988425B2 in view of in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and patented claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of a DNA vector or viral vectors MVA expressing the claimed HIV polypeptides. The patented claims do not recite viral vector ChAd.
It would have been obvious to incorporate a second viral vector ChAd for booster dose of the claimed polypeptide and to prevent neutralization of second viral vector by anti-viral vector antibody and cellular immune responses that could affect the replication of the second viral vector. It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the instant claims by incorporating viral vector ChAd with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the instant claims as compared to the patented claims.
17. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. US10815278B2 in view of in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of a DNA vector or viral vectors MVA expressing the claimed HIV polypeptides.
The patented claims are directed to vector construct comprising polynucleotide sequences that express the HIV HTI polypeptides based on the claimed SEQ ID NOs: 1-16, 100. reciting the sequences that are common to the instant application claims and patented (US10815278B2) claims.
It would have been obvious to one of the ordinary skills to make design choice to make variation in the instant claims by making choice of a plasmid vector, and viral vectors as compared to the expression vector recited in the patented claims with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the instant claims as compared to the patented claims.
18. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US11325946B2 in view of in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and patented claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of an expression cassette, an expression vector, a virus (DNA vector or viral vectors). The patented claims do not recite viral vectors are ChAd and MVA expressing the claimed HIV polypeptides. Both the instant claims and patented claims has claimed the HIV polypeptides as immunogens or the nucleotide sequences encoding the polypeptides by claiming SEQ ID NO: 1-16 and 100 that are 100% identical in the instant claims and patented claims.
It would have been obvious one of the ordinary skills to incorporate specific viral vector MVA and ChAd in the instant claims for booster dose of the claimed polypeptide and to prevent neutralization of second viral vector by anti-viral vector antibody and cellular immune responses that could affect the replication of the first or second viral vector (MVA and ChAd). It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the instant claims by incorporating viral vectors MVA or ChAd expressing the claimed polypeptides with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the instant claims as compared to the patented claims.
19. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. US11666651B2 in view of in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and patented claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) in the form of an expression cassette, an expression vector, viral vectors MVA and ChAd. Both the instant claims and patented claims has claimed the HIV polypeptides as immunogens or the nucleotide sequences encoding the polypeptides by claiming SEQ ID NOs: 1-16 and 100 that are 100% identical in the instant claims and patented claims. The patented claims have sequence identity requirement of 95% for the claimed SEQ ID NOs: 1-16 and 100 whereas the instant claims require 90% identity. The patented claims do not have requirement for DNA vector (plasmid expressing the claimed polypeptide HTI) for immunization/treatment.
It would have been obvious one of the ordinary skills to incorporate a plasmid vector-based immunization for treatment in the instant claims to have heterologous viral vectors for booster dose to prevent neutralization of second viral vector by anti-viral vector antibody and cellular immune responses that could affect the replication of the first or second viral vector (MVA and ChAd) to enable three different vectors for prime and boost regimen. It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the instant claims as compared to the patented claims with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the instant claims as compared to the patented claims.
20. Claims 1-7, 12-13, 17, 27-28, 34, 40-43 and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. US11919926B2 in view of in view of the combined teachings of Brander et al 2018 (US9988425B2, 06/05/2018, with an earlier priority to US20150050310A1 02/19/2015 and PCT Pub No W02013/110818 08/01/2013), Aelix Therapeutics 2017 (ClinicalTrial ID: NCT03204617), Ondondo et al 2016 (Molecular Therapy, vol. 24 no. 4, 832–842 Apr. 2016), Mothe et al 2015 (Journal of Translational Medicine (2015) 13:60), Boggiano et al 2005 (Eur. J. Immunol. 2005. 35: 1428–1437), Almeida et al 2012 (PLOS One, vol 7 (9), e45267), and Geleziunas 2021 (US11116774B2, 09/14/2021 with an earlier priority to US20160008374A1 published 01/14/2016).
The instant claims and patented claims both are directed to the methods of treating or preventing HIV infection in a subject comprising administering inter alia relatively conserved polypeptides of HIV (HTI) comprising polypeptides recited in SEQ ID NO: 1-16. The patented claims recited fusion polypeptide comprising SEQ ID NO: 1-16 amino acid linker is a single, dual, or triple alanine linker, and wherein the linker results in the formation of an AAA sequence in the junction region between adjoining sequences. The instant claims 42-43 recited the same amino acid linkers for linking at least two polypeptide sequences from the claimed SEQ ID NO: 1-16 claimed by the patented claims. The patented claims differ from the instant claims in delivery of the claimed fusion polypeptide in the form of DNA vaccine vector and MVA and ChAd viral expression vectors.
It would have been obvious one of the ordinary skills to use the fusion polypeptides for immunization / treatment in the instant claims that offer convenience of production and purification of the claimed polypeptides and still offer multiple combinations from 16 polypeptides SEQ ID NO: 1-16. It would have been obvious to one of the ordinary skills in the art to make an obvious variation to the instant claims by incorporating the polypeptides in DNA vector, and or viral vectors for immunization and treatment of a subject as compared to the patented claims with a reasonable expectation of success. The prior art teachings as applied for rejection of instant claims under 35 USC 103 are incorporated here in entirety to render obvious the variation in the instant claims as compared to the patented claims.
21. Relevant Prior Arts:
Bhattacharya et al 2007. US20110150915A1 (06/23/2011). Polyvalent HIV vaccine, an immunogenic composition (e.g., a vaccine) and, in particular, to a polyvalent immunogenic composition, such as a polyvalent HIV vaccine, and to methods of using same. The invention further relates to methods that use a genetic algorithm to create sets of polyvalent antigens suitable for use, for example, in vaccination strategies.
Howley et al 2011. US8021669B2 (09/20/2011). Intergenic regions as novel sites for insertion of HIV DNA sequences in the genome of modified vaccinia virus Ankara.
Perdigueroet al 2018. Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B. Viruses. 2018 Aug 13;10(8):424.
Hu et al 2018. Gag and env conserved element CE DNA vaccines elicit broad cytotoxic T cell responses targeting subdominant epitopes of HIV and SIV Able to recognize virus-infected cells in macaques. Hum Vaccin Immunother. 2018;14(9):2163-2177.
Barratt-Boyes et al 2006. Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. J Gen Virol. 2006 Jan;87(Pt 1):139-149.
Hu et al 2016. DNA Prime-Boost Vaccine Regimen To Increase Breadth, Magnitude, and Cytotoxicity of the Cellular Immune Responses to Subdominant Gag Epitopes of Simian Immunodeficiency Virus and HIV. J Immunol. 2016 Nov 15;197(10):3999-4013.
Conclusion
22. No claims is allowed.
23. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner , Art Unit 1600