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
1. The Amendment filed November 13, 2025 in response to the Office Action of August 13, 2025 is acknowledged and has been entered. Claims 18, 20 and 22 have been cancelled. Claims 1, 5, and 14 have been amended.
2. Claims 1-17, 19, and 21 are currently being examined.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
3. Claim(s) 1-10, 12, 13, 19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize”.
Wegmann teaches a method of inducing an immune response against a human immunodeficiency virus in a subject in need thereof, the method comprising administering to the subject: (a) a first vaccine comprising one or more recombinant adenovirus vectors, preferably Ad26 vectors, encoding one or more of SEQ ID NOs: 1, 2, 3, 4, 5 and 18; and (b) a second vaccine comprising a poxvirus vector according to claim 1, wherein the first vaccine is a priming vaccine and the second vaccine is a boosting vaccine, or wherein the second vaccine is a priming vaccine and the first vaccine is a boosting vaccine.
In claims 1-3 Wegmann teaches
1. A poxvirus vector comprising nucleic acid encoding: (a) a first HIV envelope (Env) antigen comprising the amino acid sequence of SEQ ID NO: 18; (b) a second HIV Env antigen different from the first HIV Env antigen; (c) a third antigen and a fourth antigen, being two different HIV Gag antigens; and (d) a fifth antigen and a sixth antigen, being two different HIV Pol antigens.
2. The poxvirus vector of claim 1, wherein: the second HIV Env antigen comprises the amino acid sequence of SEQ ID NO: 5, the third and fourth antigens comprise the amino acid sequence of SEQ ID NO: 1 and SEQ ID NO: 2, respectively; and the fifth and the sixth antigens comprise the amino acid sequence of SEQ ID NO: 3 and SEQ ID NO: 4, respectively.
3. The poxvirus vector of claim 1, wherein the third and the fifth antigens are fused into a first Gag-Pol fusion antigen that comprises the amino acid sequence of SEQ ID NO: 28, and the fourth and the sixth antigens are fused into a second Gag-Pol fusion antigen that comprises the amino acid sequence of SEQ ID NO: 29.
SEQ ID NO: 5 of Wegmann comprises the currently claimed SEQ ID NO: 1. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 18 of Wegmann comprises the currently claimed SEQ ID NO: 2. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 28 of Wegmann comprises the currently claimed SEQ ID NO: 3. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 29 of Wegmann comprises the currently claimed SEQ ID NO: 4. See Appendix of Office Action of 08/13/2025.
Wegmann teaches the priming and boosting immunizations described herein for inducing an immune response can be combined with standard treatment, e.g., antiretroviral therapy (ART). See ¶¶ 0196-0201.
Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention. See ¶ 0196.
Wegmann teaches ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. See ¶ 0198.
Wegmann teaches pharmaceutically acceptable carriers for the compositions of the invention. See ¶¶ 0134-0135 and 0141-0142.
Wegmann teaches using AD26 and MVA vectors. See ¶¶ 0020,0024-0030, 0034, and 0242-0244
Wegmann teaches treating with 108 or 1012 viral particles. See ¶¶ 0132, 0144, 0187, 0193 and 0244
Wegmann teaches is a subject is administered four different adenovirus 26 vectors, together encoding HIV antigens comprising SEQ ID NOs: 5, 18, 28 and 29, wherein the vectors are present in a 1:1:1:1 ratio and are administered at a total dose of 5×1010 viral particles in 0.5 mL by intramuscular injection at weeks 0 and 12, followed by administration of an MVA vector encoding HIV antigens comprising SEQ ID NOs: 5, 18, 28 and 29, at a dose of about 108 plaque forming units per 0.5 mL injection administered intramuscularly at weeks 24 and 48. See ¶¶ 0178-0179, 0185, 0187, and 0188.
Wegmann teaches as set forth above, but does not teach treating with neutralizing antibodies.
Liu teaches HIV-1 fusion polypeptides, polynucleotides encoding such fusion polypeptides, vectors expressing such fusion polypeptides for use in eliciting an immune response against HIV-1. See abstract.
Liu teaches the fusion polypeptides can comprise Gag, Pol, and Env proteins. See ¶¶ 0010, 0011, 0166 and 0547.
Liu teaches administering the fusion polypeptides with antiretroviral therapy (ART). See ¶¶ 0496, 0504, 0652, and 0684-0707.
Liu teaches additionally administering a broadly neutralizing antibody. See ¶¶ 0409-0412. Liu teaches that the neutralizing antibody can bind a CD4 binding site (CD4bs). See ¶¶ 0413-0418.
Liu teaches that the neutralizing antibody can be PGT121, PGDM1400, and/or VRC07-523LS anti-HIV antibodies. See ¶¶ 0419-0421, 0734, 0738, 0740, and 0746.
Liu teaches administering compositions at least 1 week, 2 weeks, 3 weeks or 1 month apart, e.g., at least 2, 3, 4, 5 or 6 months, apart. See ¶¶ 0361, 0664 and 0687. .
Mkhize teaches the neutralization profiles of broadly neutralizing antibodies (bNAbs) against the envelope sequences of breakthrough HIV infections. Background and Methods.
Mkhize teaches that 91% of viruses were neutralized by the VRC07-523LS antibody. See Results. Mkhize teaches that 97% of viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. See Results.
Mkhize teaches that combinations of bNAbs need to be used to improve coverage of subtype C viruses. See Conclusion.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Wegmann, Liu and Mkhize and administer Gag, Pol, and Env protein vaccines of Wegmann in combination with bNAbs of Liu and Mkhize because Wegmann teaches a method of inducing an immune response against human HIV with the claimed Gag/Pol/Env proteins in Ad26 and MVA vectors, Liu teaches stimulating an anti-HIV immune response with Gag/Pol/ Env proteins in combination with bNAbs and ART, and Mkhize teaches that 97% of breakthrough HIV viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. One of skill in the art would have been motivated to combine and optimize the teachings of Wegmann, Liu and Mkhize and treat with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs after ART treatment to stimulate the most effective anti-HIV immune response in the appropriate time frame because Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
Response to Arguments
4. Applicant argues that as currently amended, independent claim 1 recites a method of inducing an immune response against HIV in an HIV-infected human subject undergoing antiretroviral therapy (ART), comprising administering an adenovirus vaccine, administering a poxvirus vaccine, and administering two or more anti-HIV broadly neutralizing antibodies, wherein the human subject has undergone ART for at least 48 weeks prior to being initially administered the adenovirus vaccine, and wherein the suppressive ART is stopped after the initial administration of the two or more anti-HIV bNAbs. Amended independent claim 14 similarly recites a method with specific dosing and timing parameters, including the same limitations regarding ART duration prior to vaccine administration and ART discontinuation after bNAb administration.
Applicant argues that the amended claims are patentable over the cited prior art because the references fail to teach or suggest the critical limitations added to independent claims 1 and 14, which define a specific therapeutic approach for HIV-infected subjects who are already established on long-term ART.
Applicant argues that Barouch teaches a study of "healthy, HIV-1-uninfected participants" who were "considered at low risk for HIV-1 infection." (P. 234, Methods.) Therefore, Barouch does not teach or suggest treating HIV-infected subjects who are already undergoing antiretroviral therapy.
Applicant argues that Wegmann similarly teaches methods for both "prophylactic purposes" in "subjects who have not been previously infected with HIV" and "therapeutic purposes" in "subjects already infected with HIV". ( [0168]-[0170].) Therefore, Wegmann '938 also does not teach or suggest administering vaccines to subjects who are already undergoing antiretroviral therapy.
Applicant argues that although Wegmann '938 teaches that "priming and boosting immunizations described herein for inducing an immune response can be combined with standard treatment, e.g., antiretroviral therapy (ART)" and discusses "interruption (also referred to as discontinuation)" of ART "after completion of a priming/boosting immunization" ( [0196]-[0199]), Wegmann '938 does not teach the specific limitation of "the human subject has undergone ART for at least 48 weeks prior to being initially administered the adenovirus vaccine" as recited by amended claim 1. Critically, Wegmann '938 does not teach the limitation of "the suppressive ART is stopped after the initial administration of the two or more anti-HIV bNAbs" as recited by amended claim 1, which represents a specific therapeutic approach distinct from general ART discontinuation after completion of immunization.
Applicant argues that Langedijk, Liu, and Mkhize fail to cure the deficiencies noted above. In particular, Liu teaches that "the subject is not receiving antiretroviral therapy (ART) or ART is discontinued prior to administration of the one or more compositions" and that "ART is discontinued after one or more administrations of the compositions". ( [0379]-[0380].) However, Liu does not teach the specific timing requirement that "the human subject has undergone ART for at least 48 weeks prior to being initially administered the adenovirus vaccine" as recited by amended claim 1. Moreover, Liu does not teach the specific therapeutic approach of "the suppressive ART is stopped after the initial administration of the two or more anti-HIV bNAbs" as recited by amended claim 1, which is essential to the claimed method of inducing immune control that allows ART discontinuation following the specific sequence of vaccine and bNAb administration.
Applicant argues that accordingly, the combination of prior art references fails to teach or suggest the specific patient population defined by "the human subject has undergone ART for at least 48 weeks prior to being initially administered the adenovirus vaccine" and the critical therapeutic step of "the suppressive ART is stopped after the initial administration of the two or more anti-HIV bNAbs" as recited by independent claim 1. These limitations define a novel therapeutic approach that is not taught or suggested by the cited prior art references, either individually or in combination. The remaining claims 2-10, 12, 13, 19, and 21 depend from independent claim 1, and are patentable over the prior art for the same reasons.
Applicant’s arguments have been considered and have been found partially persuasive. The rejection over Barouch is withdrawn in view of Applicant’s amendments. However, the rejection over Wegmann in view of the cite references is maintained.
Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
Additionally, changing the order of performing process steps is prima facie obvious in the absence of new or unexpected results. See MPEP 2144.04(C). Thus, Applicant’s arguments are not found persuasive and the rejections over Wegmann are maintained for the reasons previously set forth and above.
5. Claim(s) 11 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize” as applied to 1-10, 12, 13, 19, and 21 above, and further in view of NCT03721510 (A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults March 03, 2019), “NCT” and Gaudinski et al. (The Lancet HIV, Oct. 2019 Volume 6, Issue 10, e667- e679), “Gaudinski”.
Wegmann, Liu and Mkhize teach as set forth above, but do not teach the antibody bNAbs doses.
NCT teaches PGT121, VRC07-523LS and PGDM1400 are recombinant human IgG1 monoclonal antibodies that target a V3 glycan-dependent epitope region of the HIV envelope protein and the CD4 binding site (CD4bs) of the HIV envelope protein. PGT121, VRC07-523LS and PGDM1400 mAbs were chosen for this study because of their potency, their ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, e.g., their capacity to robustly prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys. See Detailed Description.
NCT teaches using intravenous doses of 20 mg/kg and 30 mg/kg for each antibody for the study. See Arms and Interventions.
Gaudinski teaches a dose-escalation clinical trial of VRC07-523LS. See abstract.
Gaudinski teaches four groups received a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07-523LS, and one group received a single 5 mg/kg subcutaneous dose. Two groups received three doses of either 20 mg/kg intravenous VRC07-523LS, or 5 mg/kg subcutaneous VRC07-523LS at 12-week intervals. See Abstract and Figure 1.
Gaudinski teaches that they did not observe any serious adverse events or dose-limiting toxic effects. See abstract and Table 2.
Gaudinski teaches that VRC07-523LS is safe and well tolerated is a strong and practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. See abstract and paragraph bridging e677-e668.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Wegmann, Liu, Mkhize, NCT and Gaudinski and optimize the dose of bNAbs around the doses taught by NCT and Gaudinski to maximize the anti-HIV immunity while minimizing side effects. One would have been motivated to use PGT121, VRC07-523LS and PGDM1400 and optimize the administered doses taught by the art because NCT teaches that they have the ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, and Gaudinsk teaches that VRC07-523LS is safe and well tolerated and did not exhibit any serious adverse events or dose-limiting toxic effects.
Response to Arguments
6. Applicant argues that independent claim 14 is now amended similarly to claim 1, and includes the limitations that "the human subject has undergone ART for at least 48 weeks prior to the initial administration" of an adenovirus vaccine, and that "the suppressive ART is stopped after the initial administration of the anti-HIV bNAbs". Claims 15-17 depend from independent claim 14, and claim 11 depends from independent claim 1.
Applicant argues that accordingly, claims 11 and 14-17 are patentable over Barouch and Wegmann '938 for the same reasons as discussed above, and the additional references Langedijk, Liu, Mkhize, NCT, and Gaudinski fail to cure the deficiencies of Barouch and Wegmann '938.
Applicant argues that in particular, NCT teaches inclusion criteria for HIV-infected volunteers including "On antiretroviral therapy for a minimum of 24 months, with plasma HIV-1 RNA levels of < 50 copies/ml for at least 12 months". (Specific inclusion criteria for HIV-uninfected volunteers (Group 2), 4.) Therefore, NCT does not teach the specific limitation of "the human subject has undergone ART for at least 48 weeks prior to being initially administered the adenovirus vaccine" as recited by independent claims 1 and 14. Furthermore, NCT does not teach the critical therapeutic approach of stopping ART after bNAb administration as recited by independent claims 1 and 14.
Applicant argues that Gaudinski teaches dose-escalation studies of VRC07-523LS. However, Gaudinski does not teach administering vaccines to subjects undergoing ART or the specific timing and therapeutic approach recited by amended claims 1 and 14
Applicant’s arguments have been considered, but have not been found persuasive with respect the rejections over Wegmann. NCT and Gaudinski do not need to teach that "the human subject has undergone ART for at least 48 weeks prior to the initial administration" of an adenovirus vaccine, and that "the suppressive ART is stopped after the initial administration of the anti-HIV bNAbs" because these limitations are made obvious over Wegmann for the reasons set forth above.
Additionally, the NCT inclusion criteria of being on antiretroviral therapy for a minimum of 24 months prior to treatment with the bNAbs, falls within the claimed open ended range of ART for at least 48 weeks prior to the initial administration with the bNAbs. NCT does not teach away from the claimed methods.
Thus, Applicant’s arguments are not found persuasive and the rejections over Wegmann are maintained for the reasons previously set forth and above.
Double Patenting
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.
7. Claims 1-10, 12, 13, 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,229,693 B2 (Wegmann et al. Jan. 25, 2022) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize”.
The ’693 claims are drawn to:
1. A poxvirus vector comprising nucleic acid encoding: (a) a first HIV envelope (Env) antigen comprising the amino acid sequence of SEQ ID NO: 18; (b) a second HIV Env antigen different from the first HIV Env antigen; (c) a third antigen and a fourth antigen, being two different HIV Gag antigens; and (d) a fifth antigen and a sixth antigen, being two different HIV Pol antigens.
2. The poxvirus vector of claim 1, wherein: the second HIV Env antigen comprises the amino acid sequence of SEQ ID NO: 5, the third and fourth antigens comprise the amino acid sequence of SEQ ID NO: 1 and SEQ ID NO: 2, respectively; and the fifth and the sixth antigens comprise the amino acid sequence of SEQ ID NO: 3 and SEQ ID NO: 4, respectively.
3. The poxvirus vector of claim 1, wherein the third and the fifth antigens are fused into a first Gag-Pol fusion antigen that comprises the amino acid sequence of SEQ ID NO: 28, and the fourth and the sixth antigens are fused into a second Gag-Pol fusion antigen that comprises the amino acid sequence of SEQ ID NO: 29.
4. The poxvirus vector of claim 1, wherein the first HIV Env antigen is encoded by SEQ ID NO: 41.
5. The poxvirus vector of claim 3, wherein the first HIV Env antigen is encoded by SEQ ID NO: 41; the second HIV Env antigen is encoded by SEQ ID NO: 39; the first Gag-Pol fusion antigen is encoded by SEQ ID NO: 38; and the second Gag-Pol fusion antigen is encoded by SEQ ID NO: 40.
6. The poxvirus vector of claim 1, wherein the poxvirus vector is a recombinant Modified Vaccinia virus Ankara (MVA) vector.
7. The poxvirus vector of claim 6, wherein the MVA vector comprises MVA-BN or derivatives thereof.
8. The poxvirus vector of claim 6, wherein the poxvirus vector is a recombinant MVA vector, and wherein the first Gag-Pol fusion antigen and the second Env antigen are inserted into intergenic region (IGR) 44/45 of the MVA genome, and the second Gag-Pol fusion antigen and the first Env antigen are inserted into IGR 88/89 of the MVA genome.
9. The poxvirus vector of claim 8, wherein the first Gag-Pol fusion antigen and the second Gag-Pol fusion antigen are each under control of a separate Pr13.5 promoter, and the first Env antigen and the second Env antigen are each under control of a separate PrHyb promoter.
10. A vaccine comprising a poxvirus vector according to claim 1 and a pharmaceutically acceptable carrier.
11. A vaccine combination comprising: (a) a first vaccine composition comprising an immunologically effective amount of a poxvirus vector according to claim 1; and at least one of: (b) (i) a second vaccine composition comprising an immunogenically effective amount of one or more adenovirus vectors encoding one or more of the first, second, third, fourth, fifth and sixth antigens; and (b) (ii) a third vaccine composition comprising one or more polypeptides comprising an immunogenically effective amount of an isolated HIV antigenic polypeptide, wherein the first composition, and second and/or third composition are present in the same composition or in one or more different compositions.
12. The vaccine combination of claim 11, wherein the second vaccine composition comprises recombinant Ad26 vectors together encoding SEQ ID NOs: 18, 5, 1, 2, 3 and 4.
13. The vaccine combination of claim 11, wherein the one or more isolated HIV antigenic polypeptides in the third vaccine composition comprise: (i) a polypeptide comprising residues 30-708 of the amino acid sequence of SEQ ID NO: 7, or (ii) a polypeptide comprising residues 30-724 of SEQ ID NO: 36; or (iii) both polypeptides (i) and (ii).
14. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising administering to the subject the vaccine of claim 10.
15. A method of inducing an immune response against a human immunodeficiency virus in a subject in need thereof, the method comprising administering to the subject: (a) a first vaccine comprising one or more recombinant Ad26 adenovirus vectors, encoding one or more of SEQ ID NOs: 1, 2, 3, 4, 5 and 18; and (b) a second vaccine comprising a poxvirus vector according to claim 1, wherein the first vaccine is a priming vaccine and the second vaccine is a boosting vaccine, or wherein the second vaccine is a priming vaccine and the first vaccine is a boosting vaccine.
16. The method of claim 15, further comprising administering to the subject one or more isolated HIV antigenic polypeptides, at about the same time as the boosting vaccine, wherein the one or more HIV antigenic polypeptides comprise (i) a polypeptide comprising residues 30-708 of the amino acid sequence of SEQ ID NO: 7, or (ii) a polypeptide comprising residues 30-724 of SEQ ID NO: 36; or (iii) both polypeptides (i) and (ii), and wherein the one or more isolated HIV antigenic polypeptides is in the same composition as the boosting vaccine or in a composition separate from the boosting vaccine.
17. The method according to claim 14, wherein the subject is a subject that has been infected with HIV.
18. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising administering to the subject the vaccine combination of claim 11.
19. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising administering to the subject the vaccine combination of claim 12.
20. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising administering to the subject the vaccine combination of claim 13.
SEQ ID NO: 5 of the ‘693 claims comprises the currently claimed SEQ ID NO: 1. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 18 of the ‘693 claims comprises the currently claimed SEQ ID NO: 2. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 28 of the ‘693 claims comprises the currently claimed SEQ ID NO: 3. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 29 of the ‘693 claims comprises the currently claimed SEQ ID NO: 4. See Appendix of Office Action of 08/13/2025.
Wegmann, Liu and Mkhize teach as set forth above.
The ‘693 claims teach as set forth above, but do not teach treating with ART or bNAbs
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘693 claims, Wegmann, Liu and Mkhize and administer Gag, Pol, and Env protein vaccines of the ‘693 claims or Wegmann in combination with bNAbs of Liu and Mkhize because the ‘693 claims and Wegmann teach a method of inducing an immune response against human HIV with the claimed Gag/Pol/Env proteins in Ad26 and MVA vectors, Liu teaches stimulating an anti-HIV immune response with Gag/Pol/ Env proteins in combination with bNAbs and ART, and Mkhize teaches that 97% of breakthrough HIV viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. One of skill in the art would have been motivated to combine and optimize the teachings of the ‘693 claims, Wegmann, Liu and Mkhize and treat with Gag/Pol/ Env proteins of the ‘693 claims or Wegmann in combination with bNAbs and ART to stimulate the most effective anti-HIV immune response in the appropriate time frame because Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
8. Claims 11 and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,229,693 B2 (Wegmann et al. Jan. 25, 2022) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize” as applied to claims 1-10, 12, 13, 19 and 21 above and further in view of NCT03721510 (A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults March 03, 2019), “NCT” and Gaudinski et al. (The Lancet HIV, Oct. 2019 Volume 6, Issue 10, e667- e679), “Gaudinski”.
The ‘693 claims, Wegmann, Liu and Mkhize teach as set forth above, but do not teach the antibody bNAbs doses.
NCT and Gaudinski teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘693 claims, Wegmann, Liu, Mkhize, NCT and Gaudinski and optimize the dose of bNAbs around the doses taught by NCT and Gaudinski to maximize the anti-HIV immunity while minimizing side effects. One would have been motivated to use PGT121, VRC07-523LS and PGDM1400 and optimize the administered doses taught by the art because NCT teaches that they have the ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, and Gaudinski teaches that VRC07-523LS is safe and well tolerated and did not exhibit any serious adverse events or dose-limiting toxic effects.
9. Claims 1-10, 12, 13, 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,723,970 B2 (Wegmann et al. Aug. 15, 2023) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize”.
The ’970 claims are drawn to:
1. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising: administering a first vaccine comprising an immunogenically effective amount of one or more recombinant adenovirus vectors, encoding one or more HIV antigens comprising an amino acid sequence of any one or more of SEQ ID NOs: 1-5, 18, 28, and 29, and a carrier; (ii) administering a second vaccine comprising a poxvirus vector comprising nucleic acid encoding: (a) a first HIV envelope (Env) antigen comprising the amino acid sequence of SEQ ID NO: 18; (b) a second HIV Env antigen different from the first HIV Env antigen; (c) a third antigen and a fourth antigen, being two different HIV Gag antigens; and (d) a fifth antigen and a sixth antigen, being two different HIV Pol antigens, and a carrier; wherein steps (i) and (ii) are conducted in either order, with one of the steps for priming immunization and the other step for boosting immunization.
2. The method according to claim 1, wherein the method further comprises administering to the subject a third vaccine comprising an immunogenically effective amount of one or more isolated HIV antigenic polypeptides, and a carrier.
3. The method according to claim 2, wherein the third vaccine is administered together with the first vaccine or the second vaccine.
4. The method according to claim 2, wherein the third vaccine is administered at about the same time as the vaccine used for the boosting vaccine.
5. The method according to claim 2, wherein the one or more isolated HIV antigenic polypeptides in the third vaccine comprise (i) a polypeptide comprising residues 30-708 of the amino acid sequence of SEQ ID NO: 7; or (ii) a polypeptide comprising residues 30-724 of SEQ ID NO: 36; or (iii) both polypeptides (i) and (ii), and wherein the one or more isolated HIV antigenic polypeptides are in the same composition as the boosting vaccine and/or priming vaccine or in a composition separate from the boosting vaccine and/or priming vaccine.
6. The method according to claim 5, wherein the first vaccine comprises a first adenovirus vector encoding a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 18 and a second adenovirus vector encoding a HIV antigen comprising the amino acid sequence of SEQ ID NO: 5, and wherein the first vaccine is administered to the subject one or more times for priming immunization, the second vaccine is administered to the subject one or more times for boosting immunization, and the third vaccine is administered to the subject together with the second vaccine one or more times for the boosting immunization.
7. The method according to claim 6, wherein the first vaccine comprises one or more additional adenovirus vectors encoding one or more HIV antigens comprising the amino acid sequences of SEQ ID NOs: 1-4, 28, and 29.
8. The method according to claim 6, wherein the poxvirus vector encodes further HIV antigens comprising one or more of the amino acid sequences of SEQ ID NOs: 1-5, 28 and 29.
9. The method according to claim 1, wherein the one or more recombinant adenovirus vectors are Ad26 vectors.
10. The poxvirus vector according to claim 1, wherein the poxvirus vector is a recombinant Modified Vaccinia virus Ankara (MVA) vector.
11. The poxvirus vector according to claim 10, wherein the MVA vector comprises MVA-BN or derivatives thereof.
12. The method according to claim 1, wherein the subject has been infected with HIV prior to the priming administration.
13. The method according to claim 1, further comprising administering a latent viral reservoir purging agent to the subject.
14. The method according to claim 13, wherein the latent viral reservoir purging agent is a TLR7 modulator.
15. The method according to claim 1, wherein the subject is further undergoing antiretroviral therapy (ART).
16. The method according to claim 15, wherein the subject undergoes interruption of ART after completion of a priming/boosting immunization.
17. The method according to claim 16, wherein the interruption of ART is initiated after completion of an Ad26 priming immunization and MVA boosting immunization.
18. The method according to claim 17, wherein the MVA boosting immunization is administered together with one or more isolated HIV Env gp140 proteins.
19. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject in need thereof, the method comprising administering to the subject, the method comprising (a) administering to the subject: (i) a recombinant adenovirus 26 (rAd26) vector encoding a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 18; (ii) a rAd26 vector encoding an antigen comprising the amino acid sequence of SEQ ID NO: 5; (iii) a rAd26 vector encoding an antigen comprising the amino acid sequence of SEQ ID NO: 28; and (iv) a rAd26 vector encoding an antigen comprising the amino acid sequence of SEQ ID NO: 29; (b) administering to the subject: (i) a recombinant Modified Vaccinia virus Ankara (MVA) or MVA-BN vector comprising nucleic acid encoding (i,a) a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 18; (i,b) a HIV Env antigen comprising the amino acid sequence of SEQ ID NO: 5; (i,c) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 28; (i,d) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 29.
20. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a human subject in need thereof, the method comprising: (a) administering to the subject: (i) an recombinant Modified Vaccinia virus Ankara (MVA) or MVA-BN vector comprising nucleic acid encoding (i,a) a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 18; (i,b) a HIV Env antigen comprising the amino acid sequence of SEQ ID NO: 5; (i,c) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 28; (i,d) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 29; (b) administering to the subject: (i) an MVA or MVA-BN vector comprising nucleic acid encoding (i,a) a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 18; (i,b) a HIV Env antigen comprising the amino acid sequence of SEQ ID NO: 5; (i,c) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 28; (i,d) a HIV Gag-Pol fusion antigen comprising the amino acid sequence of SEQ ID NO: 29; and one or more of (ii, a) an isolated HIV gp140 protein having the sequence of amino acids 30-708 of SEQ ID NO: 7; and (ii, b) an isolated HIV gp140 protein having the sequence of amino acids 30-724 of SEQ ID NO: 36; and (iii) an aluminum phosphate adjuvant.
SEQ ID NO: 5 of the ‘970 claims comprises the currently claimed SEQ ID NO: 1. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 18 of the ‘970 claims comprises the currently claimed SEQ ID NO: 2. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 28 of the ‘970 claims comprises the currently claimed SEQ ID NO: 3. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 29 of the ‘970 claims comprises the currently claimed SEQ ID NO: 4. See Appendix of Office Action of 08/13/2025.
Wegmann, Liu and Mkhize teach as set forth above.
The ‘970 claims teach as set forth above, but do not teach treating with bNAbs
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘970 claims, Wegmann, Liu and Mkhize and administer Gag, Pol, and Env protein vaccines of the ‘970 claims or Wegmann in combination with bNAbs of Liu and Mkhize because the ‘970 claims and Wegmann teach a method of inducing an immune response against human HIV with the claimed Gag/Pol/Env proteins in Ad26 and MVA vectors, Liu teaches stimulating an anti-HIV immune response with Gag/Pol/ Env proteins in combination with bNAbs and ART, and Mkhize teaches that 97% of breakthrough HIV viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. One of skill in the art would have been motivated to combine and optimize the teachings of the ‘970 claims, Wegmann, Liu and Mkhize and treat with Gag/Pol/ Env proteins of the ‘970 claims or Wegmann in combination with bNAbs and ART to stimulate the most effective anti-HIV immune response in the appropriate time frame because Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
10. Claims 11 and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of 11,723,970 B2 (Wegmann et al. Aug. 15, 2023) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize” as applied to claims 1-10, 12, 13 19 and 21 above and further in view of NCT03721510 (A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults March 03, 2019), “NCT” and Gaudinski et al. (The Lancet HIV, Oct. 2019 Volume 6, Issue 10, e667- e679), “Gaudinski”.
The ‘970 claims, Wegmann, Liu and Mkhize teach as set forth above, but do not teach the antibody bNAbs doses.
NCT and Gaudinski teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘970 claims, Wegmann, Liu, Mkhize, NCT and Gaudinski and optimize the dose of bNAbs around the doses taught by NCT and Gaudinski to maximize the anti-HIV immunity while minimizing side effects. One would have been motivated to use PGT121, VRC07-523LS and PGDM1400 and optimize the administered doses taught by the art because NCT teaches that they have the ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, and Gaudinski teaches that VRC07-523LS is safe and well tolerated and did not exhibit any serious adverse events or dose-limiting toxic effects.
11. Claims 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,307,477 B2 (Tomaka et al. June 4, 2019) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize”.
The ’477 claims are drawn to:
1. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising: (i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of one or more adenovirus 26 (Ad26) vectors encoding one or more mosaic HIV gag, pol and/or env antigens and a pharmaceutically acceptable carrier; and (ii) administering to the human subject a booster vaccine comprising an immunogenically effective amount of one or more modified vaccinia ankara (MVA) vectors encoding one or more mosaic HIV gag, pol and/or env antigens and a pharmaceutically acceptable carrier.
2. The method of claim 1, wherein the booster vaccine is administered about 22-26 weeks after the primer vaccine is initially administered.
3. The method according to claim 1, wherein the primer vaccine comprises Ad26 vectors encoding three mosaic HIV antigens having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4; and the booster vaccine comprises MVA vectors encoding four mosaic HIV antigens having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.
4. The method according to claim 3, wherein the immunogenically effective amount of the Ad26 vectors encoding mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 consists of three Ad26 vectors of which a first Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 4.
5. The method according to claim 4, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10.sup.10 viral particles (vp).
6. The method according to claim 3, wherein the immunogenically effective amount of the MVA vectors encoding mosaic HIV antigens of SEQ ID NOs: 1, 2, 3, and 4 consists of two MVA vectors of which a first MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 2 and 4.
7. The method according to claim 6, wherein the first and second MVA vectors are administered at a total dose of about 1×10.sup.8 plaque forming units (pfu).
8. The method according to claim 1, further comprising re-administering the primer vaccine at about 10-14 weeks after the primer vaccine is initially administered; and re-administering the booster vaccine at about 46 to 50 weeks after the primer vaccine is initially administered.
9. The method according to claim 8, wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.
10. The method according to claim 1, wherein the human subject initiated ART during acute HIV infection.
11. The method according to claim 1, wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.
12. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising: (i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of one or more adenovirus 26 (Ad26) vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1, 3, and 4 and a pharmaceutically acceptable carrier; and (ii) administering to the human subject a booster composition comprising an immunogenically effective amount of one or more MVA vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4 and a pharmaceutically acceptable carrier, wherein the primer vaccine is re-administered at about 10-14 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 22-26 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 46-50 weeks after primer vaccine is initially administered; and wherein the human subject initiated ART during acute HIV infection.
13. The method according to claim 12, wherein the immunogenically effective amount of the Ad26 vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 consists of three Ad26 vectors of which a first Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 4.
14. The method according to claim 13, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10.sup.10 vp.
15. The method according to claim 12, wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered, the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered, and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.
16. The method according to claim 12, wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.
17. The method according to claim 1, wherein a human subject to which the primer vaccine and the booster vaccine has been administered, discontinues ART and maintains viral suppression for at least 24 weeks after discontinuing ART.
18. The method according to claim 12, wherein a human subject to which the primer vaccine and the booster vaccine has been administered, discontinues ART and maintains viral suppression for at least 24 weeks after discontinuing ART.
19. The method according to claim 13, wherein the immunogenically effective amount of the MVA vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1-4 consists of two MVA vectors of which a first MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 2 and 4.
20. The method according to claim 19, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10.sup.10 vp, and the first and second MVA vectors are administered at a total dose of about 1×10.sup.8 pfu.
SEQ ID NO: 1 of the ‘477 claims comprises the currently claimed SEQ ID NO: 1. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 2 of the ‘477 claims has 90% identity to the currently claimed SEQ ID NO: 2. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 3 of the ‘477 claims comprises the currently claimed SEQ ID NO: 3. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 4 of the ‘‘477 claims comprises the currently claimed SEQ ID NO: 4. See Appendix of Office Action of 08/13/2025.
Wegmann, Liu and Mkhize teach as set forth above.
The ‘477 claims teach as set forth above, but do not teach treating with bNAbs
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘477 claims, Wegmann, Liu and Mkhize and administer Gag, Pol, and Env protein vaccines of the ‘477 claims or Wegmann in combination with bNAbs of Liu and Mkhize because the ‘477 claims and Wegmann teach a method of inducing an immune response against human HIV with the claimed Gag/Pol/Env proteins in Ad26 and MVA vectors, Liu teaches stimulating an anti-HIV immune response with Gag/Pol/ Env proteins in combination with bNAbs and ART, and Mkhize teaches that 97% of breakthrough HIV viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. One of skill in the art would have been motivated to combine and optimize the teachings of the ‘477 claims, Wegmann, Liu and Mkhize and treat with Gag/Pol/ Env proteins of the ‘477 claims or Wegmann in combination with bNAbs and ART to stimulate the most effective anti-HIV immune response in the appropriate time frame because Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
13. Claims 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,525,123 B2 (Tomaka et al. Jan. 7, 2020) in view of US 2020/0138938 A1 (Wegmann et al. May 7, 2020), “Wegmann”, in view of US 2021/0017255 (Liu et al. Jan. 21, 2021, IDS), “Liu” and in view of Mkhize et al. (J. Int. AIDS Soc. Feb. 2021, 24(Suppl. 1): 9, Ab. No. OA03.05), “Mkhize”.
The ’123 claims are drawn to:
1. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising: (i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of one or more first adenovirus 26 (Ad26) vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1, 3, and 4, and a pharmaceutically acceptable carrier; and (ii) administering to the human subject a booster vaccine comprising an immunogenically effective amount of one or more modified vaccinia ankara (MVA) vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4, wherein the subject started ART at least four weeks prior to initial administration of the primer vaccine.
2. The method according to claim 1, wherein the immunogenically effective amount of the Ad26 vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 consists of three Ad26 vectors of which a first Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 4.
3. The method according to claim 2, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10.sup.10 viral particles (vp).
4. The method according to claim 1, wherein the immunogenically effective amount of the MVA vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1-4 consists of two MVA vectors of which a first MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 2 and 4.
5. The method according to claim 4, wherein the first and second MVA vectors are administered at a total dose of about 1×10.sup.8 plaque forming units (pfu).
6. The method of claim 1, wherein the primer vaccine is re-administered at about 10-14 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 22-26 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 46-50 weeks after the primer vaccine is initially administered.
7. The method according to claim 6, wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.
8. The method according to claim 1, wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.
9. The method according to claim 8, wherein the subject is administered an activator of latent HIV reservoir after discontinuing ART.
10. The method according to claim 1, wherein the human subject initiated ART during acute HIV infection.
11. The method of claim 1, wherein the ART comprises at least one selected from the group consisting of a nucleoside reverse transcriptase inhibitor, a non-nucleotide reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, a fusion inhibitor, an entry inhibitor and a chemokine receptor antagonist.
12. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising: (i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of a first adenovirus 26 (Ad26) vector encoding a mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encoding a mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encoding a mosaic HIV antigen of SEQ ID NO: 4, and a pharmaceutically acceptable carrier; and administering to the human subject a booster vaccine comprising an immunogenically effective amount of a first modified vaccinia ankara (MVA) vector encoding mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encoding mosaic HIV antigens of SEQ ID NOs: 2 and 4, and a pharmaceutically acceptable carrier, wherein the primer vaccine is re-administered at about 10-14 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 22-26 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 46-50 weeks after primer vaccine is initially administered; and wherein the human subject initiated ART during acute HIV infection and the human subject has sustained viremic control defined as plasma HIV RNA of less than 50 copies per ml for at least 48 weeks prior to the initial administration of the primer vaccine, optionally with one or more blips of plasma HIV RNA greater than 50 copies/ml to less than 20 copies/ml, provided that screening immediately prior to initial administration of the primer vaccine is less than 50 copies per ml.
13. The method according to claim 12, wherein the first, second, and third Ad26 vectors are at a ratio of about 2:1:1, respectively; and the first and second MVA vectors are at a ratio of about 1:1, respectively.
14. The method according to claim 12, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×1010 vp; and the first and second MVA vectors are administered at a total dose of about 1×108 pfus.
15. The method according to claim 12, wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered, the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered, and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.
16. The method according to claim 12, wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.
17. The method according to claim 16, wherein the subject is administered an activator of latent HIV reservoir comprising a histone deacetylase inhibitor after discontinuing ART.
18. The method according to claim 12, wherein the ART comprises at least one selected from the group consisting of a nucleoside reverse transcriptase inhibitor, a non-nucleotide reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, a fusion inhibitor, an entry inhibitor and a chemokine receptor antagonist.
19. The method according to claim 12, wherein the primer vaccine and the booster vaccine are administered via intramuscular injection.
20. The method according to claim 12, wherein administration of the primer vaccine and booster vaccine induces an immune response against multiple clades of HIV in the subject.
SEQ ID NO: 1 of the ‘123 claims comprises the currently claimed SEQ ID NO: 1. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 2 of the ‘123 claims has 90% identity to the currently claimed SEQ ID NO: 2. See Appendix .
SEQ ID NO: 3 of the ‘123 claims comprises the currently claimed SEQ ID NO: 3. See Appendix of Office Action of 08/13/2025.
SEQ ID NO: 4 of the ‘123 claims comprises the currently claimed SEQ ID NO: 4. See Appendix of Office Action of 08/13/2025.
The ‘123 claims teach as set forth above, but do not teach treating with bNAbs.
Wegmann, Liu and Mkhize teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘123 claims, Wegmann, Liu and Mkhize and administer Gag, Pol, and Env protein vaccines of the ‘123 claims or Wegmann in combination with bNAbs of Liu and Mkhize because the ‘123 claims and Wegmann teach a method of inducing an immune response against human HIV with the claimed Gag/Pol/Env proteins in Ad26 and MVA vectors, Liu teaches stimulating an anti-HIV immune response with Gag/Pol/ Env proteins in combination with bNAbs and ART, and Mkhize teaches that 97% of breakthrough HIV viruses were neutralized by the combination of PGDM1400, PGT121 and VRC07-523LS antibodies. One of skill in the art would have been motivated to combine and optimize the teachings of the ‘123 claims, Wegmann, Liu and Mkhize and treat with Gag/Pol/ Env proteins of the ‘123 claims or Wegmann in combination with bNAbs and ART to stimulate the most effective anti-HIV immune response in the appropriate time frame because Wegmann teaches one of ordinary skill in the art will be able to determine the appropriate antiretroviral treatment, frequency of administration, dosage of the ART, etc. so as to be compatible with administration of the priming/boosting immunizations of the invention and ART can be discontinued when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks. Thus one would have discontinued ART when the subject has plasma HIV RNA levels at less than 50 copies/mL for at least about 52 weeks prior to treatment with Gag/Pol/ Env proteins of Wegmann in combination with bNAbs to stimulate an anti-HIV immune response to inhibit or prevent HIV expansion and optimize treatment.
Response to Arguments
14. Applicant argues that the rejections on the grounds of non-statutory double-patenting are believed to be moot in view of the amendments to independent claims 1 and 14, and Applicant respectfully requests that the rejections are withdrawn.
Applicant's arguments have been considered and have been found partially persuasive. The rejections over the claims of 10,525,123 or 10,307,477 are withdrawn in view of Applicant’s amendments. However, the rejections of 19 and 21 over the claims of 10,525,123 or 10,307,477, because it is not clear if the ART treatment is stopped in these claims. See below.
Additionally, the rejections over the claims of 11,229,693 and 11,723,970 are maintained in view of the teachings of the claims of 11,229,693 and 11,723,970 and Wegmann, Liu, Mkhize, NCT and Gaudinski as previously set forth and above.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
15. Claims 1-17, 19, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the suppressive ART" in part (iii)-line 4. There is insufficient antecedent basis for this limitation in the claim which does not refer to “suppressive ART". The claims which depend from claim 1 are also indefinite by incorporating this limitation by reference
Claim 14 recites the limitation "the suppressive ART" in part (iii)-last two lines. There is insufficient antecedent basis for this limitation in the claim which does not refer to “suppressive ART". The claims which depend from claim 14 are also indefinite by incorporating this limitation by reference
Claim 19 recites the method of claim 1, wherein the human subject continues undergoing suppressive ART during the treatment. It is unclear if the ART treatment is stopped as now recited in amended claim 1 or if the ART treatment is continued as recited in claim 19. Thus, the scope of the claim is unclear and indefinite.
Claim 21 is drawn to a method of treating a human immunodeficiency virus (HIV) infection in a human subject in need thereof, comprising: (i) treating the human subject with an antiretroviral therapy (ART); and (ii) inducing an immune response against the HIV in the human subject using a method of claim 1. It is unclear if the ART treatment is stopped as now recited in amended claim 1 or if the ART treatment is continued as recited in part (i) of claim 21. Thus, the scope of the claim is unclear and indefinite.
Conclusion
16. All other objections and rejections recited in the Office Action of August 13, 2025 are withdrawn in view of Applicant’s amendments and arguments..
17. No claims allowed.
18. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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/Peter J Reddig/
Primary Examiner, Art Unit 1642