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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/29/2025 has been entered.
Claim Status
Claims 1-6, 10, 39-42, 46-50, 53-54, and 62 are pending. Claim 1 was amended in the Reply filed 9/29/2025. Claims 2-6, 10, 39-42, 46-50, 53-54, and 62 remain withdrawn. Claim 1 is presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-6, 10, 39-42, 46-50, and 60-62 as filed 3/08/2022) and an Applicant-defined species (subgenus) as described below in the reply filed on 1/31/2024 is acknowledged.
As noted in the previous action, it was the Examiner’s understanding that Applicant elected a narrow subgenus of patentably indistinct species of method rather than a single, disclosed species (see, e.g., Action mailed 2/16/2024 at 2-5), and that subgenus was previously identified on record (see, e.g., Action mailed 2/16/2024 at 2-5), examined, and deemed anticipated and/or obvious in view of the prior art of record (see, e.g., id).
Amended claim 1 as filed 8/28/2024 was understood to continue reading upon the originally elected subgenus of patentably indistinct species. An amendment to the preamble of claim 1 was filed in the Reply submitted 9/29/2025, but the change is understood to be directed to an intended or expected result of the recited method steps set forth in the body of claim 1, which remain unchanged relative to the previous round of examination. Therefore, instant claim 1 is understood to continue reading on the originally subgenus of patentably indistinct species.
Accordingly, the originally elected subgenus of patentably indistinct species was searched again. Following extensive search and examination, the originally elected subgenus of patentably indistinct species of method has again been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A), claims that do not read upon the originally elected species are withdrawn.
Claims 53-54 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. Election was made without traverse in the reply filed on 1/31/2024.
Claims 2-5, 10, 39-42, 46-50, 53-54, and 62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/31/2024.
Claim 1 is presently considered.
Priority
The priority claim to US Provisional Application 62/794,850 as filed 1/21/2019 is acknowledged.
Information Disclosure Statement
Examiner again notes that numerous documents are referenced throughout the originally filed disclosure but have not been placed in an IDS (see, e.g., Spec. filed 7/20/2021 at 101-104, passim). These documents are understood to be pertinent to the patentability of the invention. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope and presently recite:
1. (Previously Presented) A method of reactivating latent human immunodeficiency virus (HIV) integrated into the genome of a primary human CD4+ T cell infected with HIV, the method comprising contacting the cell with a FOXO1 inhibitor that reactivates latent HIV integrated into the genome of the cell, wherein the contacting takes place in the absence of an exogenously supplied immunodeficiency virus immunogen, wherein the FOXO1 inhibitor is AS1842856 (5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid) or a pharmaceutically acceptable salt thereof, wherein latent HIV integrated into the genome of the cell is reactivated.
Applicable claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
The term “human immunodeficiency virus (HIV)” is interpreted in view of the originally filed disclosure, and is understood to read upon “any of a variety of HIV subtypes and quasispecies” (see, e.g., Spec. filed 7/20/2021 at ¶[0031]). However, the meaning of “any of a variety of” statement is not defined or explained on record. In the absence of a clear definition of what HIV sequences are included or excluded in the scope of the claim, the term is given the broadest, reasonable interpretation in view of the originally filed disclosure. Specifically, the term “human immunodeficiency virus (HIV)” is reasonably understood to include any “latent” HIV-related viral elements integrated into the genome of a cell capable of non-exogenously suppling any immunodeficiency virus immunogen (see, e.g., Spec. filed 7/20/2021 at ¶¶[0031], [0032]). This is reasonable because the exemplified embodiments use model systems for HIV infections, including K562 cells, J-Lat clonal cell lines, and human-modified cell lines containing GFP-reporter genes and Δenv provirus (see, e.g., Spec. filed 7/20/2021 at Example 1 at ¶¶[00243]-[00244], [00246]; at Example 2 at ¶¶[00248]-[00253]; at Example 3 at ¶¶[00254]-[0025]; at Example 3 at ¶[00255]). Accordingly, claim 1 is reasonably inferred to read upon prior art model systems for HIV infections, including, for example, the replication competent HIV-1 GFP reporter virus identified as NLENG1-ESI (see, e.g., Trinite1 at pages 5-7 at § “A Foxo1 inhibitor accelerates HIV-1 replication”, Figure 6 at pages 8-9, 10 at col II at § Viruses),
Regarding the preamble of claim 1 reciting “of reactivating latent human immunodeficiency virus (HIV) integrated into the genome of a primary human CD4+ T cell infected with HIV”, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of the claim recites the following steps:
. . .contacting the cell with a FOXO1 inhibitor . . . wherein the contacting takes place in the absence of an exogenously supplied immunodeficiency virus immunogen, wherein the FOXO1 inhibitor is AS1842856…
Accordingly, the preamble of claim 1 is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I)). As amended in the reply filed 9/29/2025, the claim is understood to be require a primary human CD4+ T cell, but such limitation would be reasonably understood to be fully satisfied by administration of AS1842856 to a human infected with HIV.
Regarding claim 1, and the added “wherein” clause stating “wherein latent HIV integrated into the genome of the cell is reactivated”, per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause does not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore is not a functional limitation. Rather, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the “wherein” is understood to be fully satisfied by all prior art embodiments that satisfy the active method steps set forth in the body of claim 1, namely
. . .contacting the [primary human CD4+ T] cell with a FOXO1 inhibitor . . . wherein the contacting takes place in the absence of an exogenously supplied immunodeficiency virus immunogen, wherein the FOXO1 inhibitor is AS1842856….
Accordingly, the “wherein” of claim 1 is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I)).
Amended claim 1 recites “a FOXO1 inhibitor”, which has now been explicitly limited to the small molecule of AS1842856.
Claim 1 recites the phrase “that reactivates latent HIV integrated into the genome of the cell”. This statement is not a functional limitation because it does not correspond to any structure/function relationship of record. Accordingly, this phrase is interpreted as equivalent to a “wherein” clause. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the phrase “that reactivates latent HIV integrated into the genome of the cell” is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the phrase “that reactivates latent HIV integrated into the genome of the cell” is understood to be fully satisfied by any prior art method satisfying the active method steps set forth in the body of claim 1, namely
. . .contacting the [primary human CD4+ T] cell with a FOXO1 inhibitor . . . wherein the contacting takes place in the absence of an exogenously supplied immunodeficiency virus immunogen, wherein the FOXO1 inhibitor is AS1842856….
Accordingly, the clause of claim 1 is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I)).
Claim 1 recites the proviso that “contacting takes place in the absence of an exogenously supplied immunodeficiency virus immunogen”. This phrase is interpreted as described in the Specification, which identifies that “exogenously supplied” means anything “other than as a result of an immunodeficiency virus infection” (see, e.g., Spec. filed 7/20/2021 at ¶[0032]). Accordingly, “exogenously supplied” includes anything supplied by “the hand of man” (see, e.g., Spec. filed 7/20/2021 at ¶[0032]). The “immunogen” in this context is understood to include an HIV-1 envelope, a fragment thereof, or a peptide derived from an HIV-1 envelope (see, e.g., Spec. filed 7/20/2021 at ¶[0032]).
The term “about” is undefined on record. The term “about” is given its ordinary meaning in view of the biochemical arts, and is understood to mean “within 20 percent” (see, e.g., US 2009/0028832 A1 at ¶[0111]; see also US 2009/0105341 A1 at ¶[0049]; see also US 2012/0178676, at ¶[0277]). Accordingly, with respect to the instant disclosure and with prior art of record, unless the term “about” is otherwise clearly defined, the term is reasonably inferred to indicate a range either “within 20 percent” of a recited number.
The compound AS1842856 is identified as a FOXO1 inhibitor, and is also known as 5-amino-7(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid, has the CAS NO. 836620-48-5, and is understood to have the structure:
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The structure is understood to satisfy all functional limitations recited at instant claim 1.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejection
The rejection of claim 1 under 35 U.S.C. 102(a)(1) as being anticipated by Trinite et al. 2 is withdrawn in view of the amendment filed 9/29/2025 requiring contacting a primary human CD4+ T cell with AS1841856 and reactivating latent HIV.
Maintained Claim Rejections
Claim Rejections - 35 USC § 103
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Trinite et al. 3 and further in view of Oteiza et al.4 and Kim et al.5.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section, and those discussions are incorporated herein. For purposes of the instant rejection, the phrase “latent human immunodeficiency virus (HIV)” is reasonably understood to fully encompass all model systems for latent HIV infection. Additional claim interpretations are set forth below. Additional claim interpretations are set forth below.
Regarding instant claim 1 and the administration of AS1842856 to human primary CD4+ T cells, Trinite reduces to practice a method wherein the Foxo1 inhibitor of AS1842856 is contacted to primary donor human CD4+ cells6 infected with a replication competent HIV-1 GFP reporter virus identified as NLENG1-ESI (see, e.g., Trinite at pages 5-7 at § “A Foxo1 inhibitor accelerates HIV-1 replication”, Figure 6 at pages 8-9, 10 at col II at § Viruses). Trinite identifies that AS1842856 is a Foxo1 inhibitor, commercially available, and has the chemical structure of 5-amino-7(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (see, e.g., Trinite at 10 at col II at penultimate ¶). Trinite confirms the presence of “viral cDNA and RNA within the cells, and de novo virus output” (see, e.g., Trinite at 6 at col I-II at bridging ¶). In view of the experimental methods, Trinite concludes that “Foxo1 inhibitor AS1842856 accelerates HIV-1 expression” (see, e.g., Trinite at Fig. 6 on 8), and that
The Foxo1 inhibitor AS1842856 accelerated de novo viral gene expression and the sequella of infection, supporting the notion that HIV-1 suppression of Foxo1 activity may be a strategy to promote replication in resting CD4 T cells.
(see, e.g., Trinite at abs)
Accordingly, Trinite reduces to practice a method wherein AS1842856 is contacted to donor cells infected with a replication competent HIV-1 GFP reporter virus identified as NLENG1-ESI (see, e.g., Trinite at pages 5-7 at § “A Foxo1 inhibitor accelerates HIV-1 replication”, Figure 6 at pages 8-9, 10 at col II at § Viruses), and wherein such contacting resulted in accelerated de novo virus output.
The teachings of Trinite as applied to instant claims 1 have been discussed above in a preceding rejection, and those discussions are incorporated herein. This rejection is intended to address additional species pertinent to other HIV species other than cells comprising the replication competent HIV-1 GFP reporter virus identified as NLENG1-ESI (see, e.g., Trinite at pages 5-10 at § “A Foxo1 inhibitor accelerates HIV-1 replication”, Figure 6, and § Viruses).
Trinite differs from the instantly claimed invention as follows: Trinite does not explicitly reduce to practice a method of contacting primary CD4+ T cells comprising a latent HIV viral infection. Accordingly, the issue is whether or not it would have been obvious to one of ordinary skill in the art that the Foxo1 inhibitor AS1842856 could be administered to primary CD4+ T cells comprising a latent HIV infection, with a reasonable expectation of successfully reactivating HIV-1 replication in view of the prior art.
Oteiza identifies an art-recognized problem, namely that “latently HIV-1-infected CD4+T cells” are art-recognized as “a major public health problem, because they persist even when viral replication is inhibited during antiretroviral therapies”, and because they such cells can “reactivate upon antigenic stimulation”, which may lead to “the reactivation of HIV-1 replication” (see, e.g., Oteiza at 1871 at col II at final ¶). Kim is cited herein to establish an art-recognized solution, namely the “Shock and Kill” strategy of eliminating latent HIV (see, e.g., Kim at title, abs, passim). The general strategy is illustrated at Figure 1 (see, e.g., Kim at Fig. 1 on 15, reproduced in part below):
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Accordingly, the administration of a “Latency Reversing Agent” would be expected to accelerate production of HIV RNA, proteins, and/or HIV virions (see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶), and upon reactivation the cell could be targeted and “killed” (see id).
Critically, instant claim 1 is only directed to the first portion of the illustrated method (see, e.g., Kim at Fig. 1 on 15, noting only the administration of an LRA to a latently infected cell without immune-mediated clearance).
Accordingly, the pertinent question is whether or not an artisan would have reasonably identified the Foxo1 inhibitor of AS1842856 as a Latency Reversing Agent. A latency reversing agent would have been reasonably understood by an artisan to be a compound capable of increasing the production of HIV RNA, proteins, and/or HIV virions (see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶). This is pertinent because Trinite explicitly discloses that
The Foxo1 inhibitor AS1842856 accelerated de novo viral gene expression and the sequella of infection, supporting the notion that HIV-1 suppression of Foxo1 activity may be a strategy to promote replication in resting CD4 T cells.
(see, e.g., Trinite at abs)
Furthermore, Oteiza further identifies that FOXO factors, and specifically FOXO1 “effectively inhibit HIV-1 replication” and “suppress[] Tat-mediated HIV-1 transcription” (see, e.g., Oteiza at abs). Accordingly, the inhibition of FOXO1 would be expected and predicted to yield the opposite effect, namely the absence of inhibition of HIV-1 replication and the absence of suppression of Tat-mediated HIV-1 transcription (see, e.g., id). Notably, Oteiza refers to Trinite, and states that
During the course of this study, HIV-1 suppression of FoxO1 activity was proposed to be a viral strategy to promote replication in memory-resting CD4+ T cells . . . In addition, the authors showed that the FoxO1 inhibitor AS1842856 accelerates de novo viral gene expression, supporting the notion that FoxO1 can maintain silent transcription of HIV-1 through the downregulation of viral gene expression.
(see, e.g., Oteiza at 1972-1873 at bridging ¶).
Accordingly, in view of Trinite and Oteiza, an artisan would readily have appreciated that the FOXO1 inhibitor AS1842856 could be utilized to predictably and expectedly “activate HIV-1 replication in vivo” (see, e.g., Trinite at abs) in any HIV infected cells, which would include latently HIV-1-infected “memory-resting CD4+ T cells” (see, e.g., Oteiza at 1972-1873 at bridging ¶). In sum, an artisan would readily expect and predict in view of the prior art, that the FOXO1 inhibitor of AS1842856 would predictably and expectedly “activate HIV-1 replication” and gene expression in HIV-1 infected cells, including “memory-resting CD4+ T cells” (see, e.g., Oteiza at 1972-1873 at bridging ¶); therefore, an artisan would readily appreciate and conclude that AS1842856 acted as a Latency Reversing Agent (see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶), and therefore could be utilized in the “shock and kill” methodologies disclosed by Kim to predictably “activate HIV-1 replication in vivo” (see, e.g., Trinite at abs; see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): It would have been obvious to combine prior art elements (e.g., a FOXO1 inhibitor, such as AS1842856, and a resting CD4+ T cell with a latent HIV infection) according to known methods of reactivating HIV latently infected cells as taught and disclosed by Kim, because Trinite and Oteiza identify that AS1842856 acts as a Latency Reversing Agent by increasing de novo viral gene expression, and therefore an artisan would readily appreciate that AS1842856 could be utilized in the “Shock and Kill” methods disclosed by Kim, wherein such usage (or simple substitution in place of another Latency Reversing Agent) would predictably and expectedly lead to accelerated viral gene expression exactly as taught and expected in view of Trinite and Oteiza; and each prior art element merely performs its art-recognized function in combination as it does separately (see, e.g., MPEP § 2143(I)(A), (B), (G)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to administer a known compound according to a known method to achieve expected and predicted results already recognized and taught by the prior art.
Accordingly, claim 1 is rejected as obvious.
Response to Arguments
Applicant's arguments filed 9/29/2025 have been fully considered but they are not persuasive because the amendments do not render the claimed invention non-obvious in view of the prior art as set forth in the maintained rejection above. The Examiner’s prior responses of record remain pertinent and are incorporated into the instant action.
Claim interpretations are undisputed: It is the Examiner’s understanding that Applicant does not dispute any interpretation of record regarding the originally elected subgenus of patentably indistinct species, or the claim interpretation as set forth in the claim interpretation section.
Election requirement: It is the Examiner’s understanding that Applicant is disputing the original election/restriction requirement (see, e.g., Reply filed 9/29/2025 at 6 at § Election). First, Examiner notes that Applicant alleges that “Applicant was also request[sic] to elected[sic] 4 separate species” (see id), which is factually incorrect because the Requirement literally stated “Applicant is required to elect a single, disclosed species” and “[t]he election of a single species should be made by identifying a single, disclosed species as follows” (see, e.g., Requirement mailed 8/01/2023 at 4 and footnote 1), with a list of four bulleted parameters required for identification of a single, elected species (see id. at 4-6). Therefore, at no point did the Examiner require the election of more than a “single, disclosed species”. Second, it is the Examiner’s understanding that Applicant is alleging that “Applicant provided the requested species information noted” in the Requirement (see, e.g., Reply filed 9/29/2025 at 6 at § Election). This is not accurate because the Requirement requested identification of a “single, disclosed Example of record, wherein a method within Group I was exemplified on record” (see, e.g., Requirement mailed 8/01/2023 at 4 and footnote 1), and Applicant failed to identify a single, disclosed Example. Instead, Applicant responded by identifying multiple Figures, disclosures, and Examples (see, e.g., Reply filed 1/31/2024 at 6-7), and that response led to the Examiner’s understanding of record that Applicant knowingly and purposefully elected a narrow subgenus of patentably indistinct species of methods rather than a single, disclosed species as requested by the Examiner (see, e.g., Action mailed 2/16/2024 at 2-5), and that subgenus was previously identified on record (see, e.g., Action mailed 2/16/2024 at 2-5), examined, and deemed anticipated and/or obvious in view of the prior art of record (see, e.g., id). Third, it is the Examiner’s understanding that Applicant is suggesting that the Applicant’s original response to the species requirement was either improper or did not reflect their intention, and that the Examiner is at fault because “it is the Examiner’s burden to be specific in their identification and reasoning for species elections, providing ample detail in the Office Action and ensuring the applicant knows what is being elected and why, as required under 35 U.S.C. 121 and 37 CFR 1.141” (see, e.g., Reply filed 9/29/2025 at 6 at § Election). It is unclear what legal support Applicant is attempting to rely upon because 35 USC 121 and 37 CFR 1.141 merely relate to restriction requirements and fail to support Applicant’s allegations regarding a burden on the Examiner, “ample detail”, “identification and reasoning for species elections” or any burden “ensuring the applicant knows what is being elected and why”. As an initial matter, it is prima facie unclear to the Examiner what exact portion of the Requirement of record was unclear or required additional clarification. In addition, the general process for Election/restriction requirements is routine and explained in the MPEP (see, e.g., MPEP §§ 800, 803.02, 809.02(a)) and a practitioner is presumed to understand patent prosecution and understands how to properly respond to routine requirements (see, e.g., 37 C.F.R. § 11.101, 37 CFR § 11.5, and 37 CFR § 11.7) or otherwise recognize when they need to call an Examiner for additional clarification. Upon submission of a response in writing (see, e.g., 37 CFR § 1.2), examination proceeds with the understanding that a written response represents the Applicant’s intent. Here, Applicant did not avail themselves of the opportunity to contact and clarify their understanding prior to submitting a written response, and chose to not provide a “single, disclosed Example of record, wherein a method within Group I was exemplified on record” (see, e.g., Requirement mailed 8/01/2023 at 4 and footnote 1) in their written response. Furthermore, per MPEP § 809.02(a), Examiner need not “clearly identify” all possible species in a species election, and here the Examiner unambiguously requested a “single, disclosed species” defined by four identifying parameters (see, e.g., Requirement mailed 8/01/2023 at 4-6 and footnote 1). In sum, Applicants statements (see, e.g., Reply filed 9/29/2025 at 6 at § Election) do not appear to reflect the cited rules or statutes at issue, and do not appear to reflect the instant record. Accordingly, the Examiner’s position and interpretation of record is maintained (see, e.g., Action mailed 2/16/2024 at 2-5).
Relevant documents not placed on record in an IDS: Examiner has repeatedly noted that numerous documents are referenced throughout the originally filed disclosure but have not been placed in an IDS to date (see, e.g., Spec. filed 7/20/2021 at 101-104, passim; see Action mailed 2/16/2024 at 6; see Action mailed 10/17/2024 at 3-4; see Action mailed 4/28/2025 at 4). The Applicant has been repeatedly advised that such documents are understood to be pertinent to the patentability of the invention (see, e.g., Action mailed 2/16/2024 at 6; see Action mailed 10/17/2024 at 3-4; see Action mailed 4/28/2025 at 4). Accordingly, the patentability of the instant invention in view of such documents has not been considered at this time unless such documents are cited by the Examiner.
Anticipation rejection: Arguments pertaining to the anticipation rejection have been considered (see, e.g., Reply filed 9/29/2025 at 6-7), but are moot in view of the withdrawal of the rejection. Although moot, Examiner reiterates the following comments from his prior response of record to facilitate clarification of the record:
Examiner notes that the allegation that nothing in Trinite pertains to latent HIV is incorrect; Examiner notes that Trinite explicitly refers to and discusses the meaning of the experimental results in the context of “the latent reservoir” of HIV-1 that exists in CD4 T Cells (see, e.g., Trinite at 9 at col I at 3rd full ¶), and “T cell quiescence” (id. at 1 at col II at 1st full ¶). Accordingly, latent HIV particles would be apparent or at once envisaged in view of discussions of a “latent reservoir” of HIV. Regarding host cell integration, Applicant is directed to Trinite, which identifies the use DNA from cells, and the use of genomic DNA integrated HIV-1 NLA-3 proviruses (see, e.g., Trinite at 11 at col II at § Quantification of HIV-1 DNA, 11-12 at bridging ¶). Furthermore, it is well-known that HIV-1 is an RNA retrovirus, which uses a reverse transcriptase enzyme to convert its RNA genome into DNA that is then integrated into the host cell’s DNA. Therefore, in the absence to the contrary, one of ordinary skill in the HIV arts would readily appreciate and understand that HIV-1 is integrated, absent evidence to the contrary. No evidence to the contrary has been provided.
This rebuttal was provided in the previous Action (see, e.g., Action mailed 4/28/2025 at 17), but Applicant failed to acknowledge or address the citations provided by the Examiner. Accordingly, although moot in view of the withdrawal of the rejection, an artisan would readily appreciate that Trinite does in fact pertain to latent HIV infections, and to viral genomes integrated into host cells.
Obviousness Rejection: It is the Examiner’s understanding that Applicant addresses the rejection under 35 USC 103, but fails to address the merits of the rejection, any citations relied upon by the Examiner with specificity, or specifically dispute the determination of obviousness in view of MPEP § 2143(I)(A), (B), and/or (G) (see, e.g., Remarks filed 9/29/2025 at p. 8). All holdings not specifically addressed are understood to be undisputed on record.
It is the Examiner’s understanding that Applicant is alleging that the prior art did not contemplate reactivation of latent HIV (see, e.g., Reply filed 9/29/2025 at 8; see also Remarks filed 4/17/2025 at p. 6; see also Reply filed 8/28/2024 at 7 at 5th full ¶ to p. 8 at 2nd full ¶). In response to such arguments, it is noted that the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, as explained above on record, “wherein” phrases and similar clauses are interpreted consistently with MPEP § 2111.04(I), and have been fully considered on record.
It is the Examiner’s understanding that Applicant addresses the teachings of Trinite, Oteiz and Kim each alone (see, e.g., Reply filed 9/29/2025 at 8 at 3rd and 4th ¶¶; see also Remarks filed 4/17/2025 at p. 6; see also Reply filed 8/28/2024 at 7 at final ¶ to p. 8 at 1st full ¶). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
It is the Examiner’s understanding that Applicant is alleging that obviousness has not been established because “Neither Oteiza nor Kim discloses any experimental data demonstrating reactivation of a silent, integrated HIV virus by AS1842856 alone” (see, e.g., Reply filed 9/29/2025 at 8 at 4th ¶). This argument is not persuasive because the rejection has not been made in view of only the Oteiza and/or Kim reference(s), but rather in view of a combination of references including Trinite. Accordingly, In response to applicant's arguments against the references individually (or less than all references), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant alleges that there is no reasonable expectation of success in view of Trinite alone (see, e.g., Reply filed 9/29/2025 at 8 at 5th ¶). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Such arguments fail to consider or address the teachings of the combination of references at issue, and specifically fail to address the teachings of Trinite in view of Oteiza and Kim. Accordingly, such arguments are not persuasive.
If Applicant means to suggest the existence of skepticism of experts (see, e.g., Reply filed 9/29/2025 at 8 at 5th ¶), such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be conjecture of counsel unsupported by objective evidence.
It is the Examiner’s understanding that Applicant alleges that the prior art does not teach that “the compound, by itself, could awaken a clinically relevant latent reservoir - a dramatically different virological state requiring chromatin remodeling and transcriptional initiation from long-silenced proviral DNA” (see, e.g., Reply filed 9/29/2025 at 8 at 5th ¶). These features are not presently claimed. Therefore, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, arguments that the prior art does not teach unclaimed limitations are not persuasive.
It is the Examiner’s understanding that the Applicant alleges that the claimed inventors “were the first to demonstrate that flip latent, integrated HIV genomes from silent to active without additional immunogens” (see, e.g., Reply filed 9/29/2025 at 8 at 6th ¶). This statement fails to address the merits of the rejection, any citations relied upon by the Examiner with specificity, or specifically dispute the determination of obviousness in view of MPEP § 2143(I)(A), (B), and/or (G). Accordingly, such statements fail to identify how the claimed invention is patentably in view of the prior art of record.
Applicant refers to an “unexpected property” (see, e.g., Reply filed 9/29/2025 at 8 at 6th ¶). However, zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date. As explained in the rejection above, it is neither surprising nor unexpected in view of the prior art that AS1842856 could predictably be utilized as a Latency Reversing Agent (see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶), and successfully utilized in the “shock and kill” methodologies disclosed by Kim to predictably “activate HIV-1 replication in vivo” (see, e.g., Trinite at abs; see, e.g., Kim at Fig. 1 on 15, p. 14 at col I-II at bridging ¶; see rejection above).
It is the Examiner’s understanding that Applicant is alleging a lack of reasonable expectation of success (see, e.g., Reply at 8; see also Remarks filed 4/17/2025 at p. 6; see also Reply filed 8/28/2024 at 7 at 5th full ¶ to p. 8 at 2nd full ¶). Applicant fails to explain their position or address the Examiner’s express determination of a reasonable expectation of success as placed on record, which summarizes that
There would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to administer a known compound according to a known method to achieve expected and predicted results already recognized and taught by the prior art.
Applicant may mistakenly believe that a reasonable expectation of success must be shown of achieving the Applicant’s rationale, but this is incorrect. As explained in the MPEP, the Examiner may rely upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)), and a reasonable expectation of success is based upon the rationale for supporting obviousness that is relied upon by the Examiner (see, e.g., MPEP §§ 2143.01(I), 2143.02(I)-(III)). Here, the Examiner has established prima facie obviousness in view of MPEP § 2143(I)(A), (B), and/or (G). Furthermore, it is prima facie unclear why Applicant believes there would be a lack of reasonable expectation of success of administering a known drug to a known patient population to achieve a known result. Accordingly, such conclusory statements that fail to address the merits of the rejection are not persuasive.
Accordingly, all arguments have been fully considered but not found persuasive for reasons of record. Accordingly, the rejection under 35 USC 103 is maintained.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US2015/0320893 A1 (Nov. 12, 2015; cite in previous action) discloses methods of treating latent HIV infections using latency reversing agents (see, e.g., US’893 at title, abs, claims).
US 2018/0002699 A1 (Jan. 4, 2018; cite in previous action) discloses methods of treating latent HIV infections using latency reversing agents (see, e.g., US’699 at title, abs, claims).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Trinite et al. (Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells. PLoS One. 2014 Oct 16;9(10):e110719; cited in Requirement mailed 8/1/2023.
2 Trinite et al., Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells. PLoS One. 2014 Oct 16;9(10):e110719; cited in Requirement mailed 8/1/2023; hereafter “Trinite”.
3 Trinite et al., Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells. PLoS One. 2014 Oct 16;9(10):e110719; cited in Requirement mailed 8/1/2023; hereafter “Trinite”.
4 Oteiza et al.,FoxO4 negatively controls Tat-mediated HIV-1 transcription through the post-transcriptional suppression of Tat encoding mRNA. J Gen Virol. 2017 Jul;98(7):1864-1878. doi: 10.1099/jgv.0.000837. Epub 2017 Jul 12. PMID: 28699853; hereafter “Oteiza”; cited in previous action.
5 Kim et al., Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV. Cell Host Microbe. 2018 Jan 10;23(1):14-26. doi: 10.1016/j.chom.2017.12.004. PMID: 29324227; PMCID: PMC5990418; hereafter “Kim”; cited in previous action.
6 see, e.g., Trinite at 10 at col II at § Materials and Methods.