DETAILED ACTION
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 .
Claims Status
Applicant's election with traverse of Group I (claims 1-19) and the species of triphenyl phosphonium TPP mitochondrial targeting moiety, Elvitegravir anti-HIV agent, Coenzyme Q10 antioxidant and darunavir as a further agent in the reply filed on 06/05/2026 is acknowledged. The traversal is on the ground(s) that the Office has not shown serious search burden would be required. This is not found persuasive because
per PCT rule 13.1 and 13.2 search burden is not a criterion for lack of unity of invention.
Claims 4-6, 10,11-14, and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/05/2026.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3, 7-9, 15-19 are under current examination.
Information Disclosure Statements
Information Disclosure Statement (IDS) filed on 01/25/2024 and 05/08/2024 has been considered by the Examiner. A signed copy of the IDS is included with the present Office Action.
Claim Rejections - 35 USC § 112-indefinite
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.
Claims 2-3, 7-9 and 15-16 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 2 recites the limitation "the antioxidant agent or the anti-inflammatory agent. There is insufficient antecedent basis for this limitation in the claim because claim 1 recites “one or more of an anti-oxidant agent and/or an anti-inflammatory agent”. Therefore, it is unclear if “the anti-oxidant agent or the anti-inflammatory agent in claim 2 is referring back to the one or more of the anti-oxidant and/or anti-inflammatory agent. It is suggested that claim 2 can recite wherein the nanoparticle comprises the one or more anti-oxidant or anti-inflammatory agent.
Claim 3 recites wherein the anti-oxidant comprises Coenzyme Q10. There is insufficient antecedent basis for this limitation in the claim because claim 1 recites “one or more of an anti-oxidant agent and/or an anti-inflammatory agent”. Therefore, it is unclear if “the anti-oxidant agent comprising Coenzyme Q10 refers back to the one or more than one anti-oxidant required by claim 1. It is suggested that claim 3 should recite wherein the “one or more anti-oxidant agent” comprises Coenzyme Q10.
Claim 7 and 15-16 recite wherein the anti-HIV therapeutic agent comprises. Claims 7 and 15-16 are being interpreted as a selection from the group comprising for the HIV therapeutic agent. It is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022). A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. It is suggested that claim 7 and claims 15-16 can recite wherein the anti-HIV therapeutic agent is selected from the group consisting of.
Claims 8 recites that the integrase inhibitor comprises. Claim 8 is being interpreted as a selection from the group comprising for the integrase inhibitor. It is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022). A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. It is suggested that claim 8 can recite wherein the integrase inhibitor is selected from the group consisting of.
Claims 9 recites that the protease inhibitor comprises. Claim 9 is being interpreted as a selection from the group comprising for the protease inhibitor. It is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022). A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. It is suggested that claim 9 can recite wherein the protease inhibitor is selected from the group consisting of.
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.
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.
Claim(s) 1-2, 7-8,15-19, rejected under 35 U.S.C. 103 as being unpatentable over Hyde et al. (United States Patent Publication 20110293521) in view of Ahmed et al. (Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection) and Kalaritis (WO2019113210).
Hyde et al. teach a method of administering a composition to a pregnant submit who is infected with HIV, see paragraphs [0129-[0130] and [0227]-[0229]. The composition can comprise at least one virus entry inhibitor in a first formulation; an effective amount of at least one viral-replication modulator; and at least one pharmaceutically acceptable carrier or excipient, see paragraph [0012]. The at least one viral replication modulator includes elvitegravir, see paragraph [0075]. The composition can further include an antioxidant, see paragraph [0102]-[01013]. Examples of extended-release carriers for the composition having a viral replication modulator includes nanoparticles, see paragraph [0256]. One or more viral replication modulators can be present in the composition, see paragraph [0075] and [0083]. The composition reduces entry of virus into a mammal cell and modulates the activity of viral reverse transcriptase, see paragraph [0212].
Hyde does not teach that the pharmaceutical composition contains a mitochondrial targeting moiety of TPP (triphenylphosphonium), that the nanoparticles have a diameter of 100nm or less or that the nanoparticle comprises PLGA-block-PEG.
However, Ahmed et al. teach nanoparticle systems having PLGA-block-PEG functionalized with triphenylphosphonium cation that has a brain accumulating and efficient mitochondria-targeting property can be beneficial to deliver to mitochondria acting antioxidants and anti-inflammatory agents across the blood brain barrier, see abstract and pages 1-3 and 5-6. The nanoparticles are less than 80nm in size, see page 3.
Ahmed does not teach incorporation of elvitegravir with their TPP.
Kalaritis teaches driven by the plasma membrane potential, phosphonium-containing groups, such as TPP can provide for the rapid cellular uptake of active agents, followed by specific mitochondrial matrix accumulation, see page 26, lines 1-15. The cationic molecule readily permit modulation to optimize absorption and bioavailability and their in vivo attained steady state equilibrium presents an opportunity for more creative administration of drugs with serious side effects. Further, for drugs that are sensitive to oxidation, the present ionic conjugates can offer an added advantage by, in some embodiments, having an antioxidant molecule incorporated in the structure of the cationic molecule component of the conjugate, see page 27, lines 21-32 and 28 lines 1-2. The active includes elvitegravir, see claim 1 and 6. TPP containing compounds improve the therapeutic profiles of active agents, see page 26 lines 1-9.
It would have been prima facie obvious to provide the elvitegravir (anti-HIV agent) of Hyde et al. with a TPP (mitochondrial targeting moiety) as a phosphonium containing group, and to provide the nanoparticles of Hyde with a size of 90nm and with PLGA-block-PEG as suggested by Ahmed et al.
One of ordinary skill in the art would have been motivated to do so to provide for rapid mitochondrial cellular update of elvitegravir across the blood brain barrier thus improving the therapeutic profile of Elvitegravir. Nanoparticle systems less than 80nm having PLGA-block-PEG functionalized with triphenylphosphonium cation have a brain accumulating and efficient mitochondria-targeting property which is beneficial for delivery of actives to the mitochondria.
There would have been a reasonable expectation of success as Hyde et al. teaches the utilization of nanoparticles which comprise elvitegravir.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Hyde et al. (United States Patent Publication 20110293521) in view of Ahmed et al. (Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection) and Kalaritis (WO2019113210) as applied to all claims 1-2, 7-8, and 15-19 above and further in view of Velichkovska et al. (Targeted Mitochondrial COQ10 Delivery Attenuates Antiretroviral-Drug induced Senescence of Neural Progenitor Cells-IDS filed 01/25/2024).
The teachings of the modified Hyde are discussed above.
Hyde does not expressly teach that their antioxidant includes Coenzyme Q10.
Velichkovska et al. teach that coenzyme Q10 delivered by targeted nanoparticles attenuates the effects of HIV antiretroviral therapy (ART) and provides antioxidant properties in the context of mitochondrial injury, see abstract and pages 2 and 5-6 and 10. Targeted nanoparticles to the mitochondria allow a decrease of therapeutic levels to as low as 500nM, see abstract and page 10.
It would have been prima facie obvious to substitute the antioxidant of Hyde et al. for Coenzyme Q10.
One of ordinary skill in the art would have been motivated to do so because Velichkovska teaches that supplementation with the antioxidant Coenzyme Q10 before antiviral therapy helps protect against mitochondrial injury.
There would have been a reasonable expectation of success because Hyde et al. teach compositions which contain HIV antivirals and antioxidant present.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Hyde et al. (United States Patent Publication 20110293521) in view of Ahmed et al. (Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection) and Kalaritis (WO2019113210) as applied to all claims 1-2, 7-8,15-19 above and further in view of Neely et al. (Managing treatment-experienced pediatric and adolescent HIV patients: role of darunavir).
The teachings of the modified Hyde are discussed above.
Hyde teaches that the therapeutic formulation includes at least one of a protease inhibitor, reverse transcriptase inhibitor receptor antagonist, or integrase inhibitor, see claim 33.
Hyde however does not expressly teach darunavir as the type of protease inhibitor.
However, Neeley teaches that Darunavir is an HIV protease inhibitor which retains activity against viral strains that are resistant to other protease inhibitors, see abstract and pages 1-2. Neely teaches that the pediatric population whom darunavir is useful for is those who were infected with HIV at or near birth and who have developed antiviral drug resistance, see conclusion at page 19.
It would have been prima facie obvious to provide darunavir as the protease inhibitor of Hyde et al.
One of ordinary skill in the art would have been motivated to do so because darunavir is taught to provide activity against viral strains that are resistant to other protease inhibitors.
There would have been a reasonable expectation of success as darunavir is suggested to be useful in pediatric patient populations who are infected at birth or near birth and the formulation of Hyde et al. is inclusive of protease inhibitors.
Conclusion
Currently no claims are allowed and al claims are rejected.
Correspondence
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/SARAH ALAWADI/Primary Examiner, Art Unit 1619
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