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 .
Response to RCE
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been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37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.
Priority
The instant application is a 371 National Stage Entry of PCT/ US2021/028864 filed on April 23, 2021 which claims benefit to domestic provisional application No. 63/014,554 filed on April 23, 2020.
Status of Claims
Acknowledgement is made of original (2, 10, 12), previously presented (3-9, 11), and amended (1, 14), new (15-17) and cancelled (13) claims filed on March 2, 2026. Claims 1-12, 14-17 are pending in instant application.
Response to Arguments
In light of Applicant amendments filed March 2, 2026, the rejections have been modified to address claim 1’s limitation of synergy (formerly in claim 13).
Applicant's arguments filed March 2, 2026 have been fully considered but they are not persuasive.
In response to Applicant's argument that the cited references fail to provide one of ordinary skill in the art with a reasonable expectation of success (see 3/2/26 Remarks at pp. 5-8),
The cells used in Banerjee are not relevant to the claim limitations at hand; Banerjee provides a reasonable motivation for treating HPV-infection induced pre-cancerous condition with and HDAC inhibitor because vorinostat, belinostat, and panobinostat are taught to induce apoptosis in HPV-infected differentiated cells (see 11/28/25 Office Action at p. 7). The claimed invention is not directed to in vitro testing with cell types, but treating HPV-induced pre-cancerous or cancerous conditions. The prior art renders obvious all the structures of the claims (what is to be treated as taught by Trimble or Banerjee, composition components as taught by Trimble and Banerjee, a motivation to combine and an expectation of success as taught by Chen).
Applicant references instant Examples 1, 4 and Figures 5-6 as evidence of synergy (see 3/2/26 Remarks at p. 7). The proffered data is in regards to only two combinations (artesunate and panobinostat, artesunate and vorinostat). Applicant has not provided synergistic results commensurate in scope with the claims (e.g., across a variety of combinations of HDAC inhibitors and artemisinin-related compounds, see MPEP § 716.02(d)), nor does Applicant compare instant invention with the closest prior art (e.g., Chen’s combinations of artesunate and HDAC inhibitors for treating various solid cancers, see MPEP § 716.02(e)).
Moreover, there is an expectation that the claimed combination would show synergy in any scenario as long as they are used together, absent evidence of what is missing, because the prior art teaches artesunate when combined with HDAC inhibitors exhibits synergy against tumors (as taught by Chen). Synergy is expected in the instant case. Applicant would need to provide evidence via i) a variety of combinations of HDAC inhibitors and artemisinin-related compounds against HPV-induced cancerous conditions indicating a lack of predictability in synergy and/or ii) specifically claimed combinations (commensurate in scope) across a variety of cancer types indicating a lack of predictability in synergy against cancer types and the instant combination(s) are unexpected for instant method of treatment, along with iii) comparisons to the closest prior art to support an argument of unexpectedness.
In response to Applicant's argument that the cited references fail to disclose or suggest each and every element of the claims (see 3/2/26 Remarks at pp. 8-9), the Examiner notes that the previous combination of references applied are organized by claim limitation and reference teachings (see 11/28/25 Office Action pp. 7-10). Applicant does not identify the alleged missing elements.
In response to Applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (see 3/2/26 Remarks at p. 9), as noted in MPEP § 2145, any obviousness rejection is in a sense necessarily a reconstruction based on hindsight reasoning and is not improper if it takes into account only knowledge within the level of ordinary skill in the art at the time the claimed invention was made. The Examiner has provided evidence of claim limitations taught (as taught by Trimble, Banerjee, CAP, and Chen), a motivation to combine the known elements as claimed (as suggested by Chen, a known combination of the drug classes), and rationale for an expectation of success (also suggested by Chen, the known combination has synergy). Applicants have provided no evidence that the rejection is not based on knowledge available to those of ordinary skill in the art.
In response to Applicant’s arguments that the previously patented or copending claim limitations are patentably distinct (see 3/2/26 Remarks at pp. 10-12), per MPEP § 804(II)(B)(4), if the patent term filing date of an application under examination is the same or later than that of a reference application or patent, only a one-way determination of distinctness is needed in resolving the issue of double patenting, i.e., whether the invention claimed in the application would have been anticipated by, or an obvious variation of, the invention claimed in the reference application or patent. See, e.g., In re Berg, 140 F.3d 1428, 1435, 46 USPQ2d 1226, 1231-32 (Fed. Cir. 1998).
The Examiner notes that while claim wording is different, the instant limitations still read on the previously patented or copending claims as discussed in the 8/6/25 Office Action. For example,
Claim 1 of Present Application
Claim 1 of the ‘024 Patent
A method of treating a human papillomavirus (HPV)-induced pre-cancerous or cancerous condition in a human subject,
A method of treating a Human papillomavirus (HPV)-induced lesion at a genital site or an anal site in a subject thereof
An HPV-induced lesion is an HPV-induced condition. ‘024 Patent specification of sites in a subject still read on a human subject (humans have genital and anal sites).
the method comprising administering a therapeutically effective amount of one or more artemisinin-related compounds wherein the one or more artemisinin-related compounds are selected from the group consisting of artemisinin, artesunate, dihydroartemisinin, artemether, arteether, artelinic acid, and dihydrosrtemisinin propyl carbonate
comprising administering a therapeutically effective amount of one or more artemisinin-related compounds wherein the one or more artemisinin-related compounds are selected from the group consisting of artemisinin, dihydroartemisinin, artemether, arteether, artesunate, artelinic acid, and dihydrosrtemisinin propyl carbonate and
Same limitations.
and a therapeutically effective amount of one or more histone deacytlase (HDAC) inhibitors to the subject
Taught by Banerjee.
wherein the lesion is pre-malignant or malignant
An HPV-induced pre-malignant or malignant lesion is an HPV-induced condition.
wherein the administering treats the human papillomavirus (HPV)-induced condition in the human subject,
Reads on “treating”.
And wherein the effect of the one or more artemisinin-related compounds for treating the HPV-induced condition and the effect of the HDAC-inhibitor for treating the HPV-induced condition are synergistic/
Taught by Chen.
While instant claim 1 may appear to “lack” the previously patented limitations, the previously patented limitations are more narrowed in specific, encompassed by the instant claims in view of Chen and Banerjee.
The rejections have been modified in light of claim amendments (Chen teachings) and new claims (Trimble and Babna).
Modified Rejections
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.
Claims 1-12, 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Trimble et. al.1 in view of Chen et. al.2, Banerjee et. al.3 as exemplified by CAP4.
Regarding claims 1-2, 4, 12 and administering an artemisinin-related compound to treat an HPV-induced precancerous condition or claim 14 and a pharmaceutical composition comprising artesunate, Trimble teaches administering artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3) caused by HPV (see Trimble at Abstract and at p. 189 right col. ¶2), a pre-cancerous lesion condition (see Trimble at p. 188 right col. ¶1).
Regarding claim 3 and cervical dysplasia, exemplary reference CAP explains that CIN is used synonymously with cervical dysplasia (see CAP at p. 1 ¶2).
Regarding claims 11-12 and identifying the subject, Trimble teaches identifying adult, immunocompetent women who had a biopsy-confirmed tissue diagnosis of CIN2/3, a visible residual lesion, and detectable HPV for participation in the treatment study (see Trimble at p. 189 right col. ¶2).
Regarding claims 9-10, 14-15, and administration routes, Trimble teaches artesunate has cytotoxic effects on human solid tumors with clinical trials for the systemic oral and intravenous administration routes (see Trimble at p. 189 left col. ¶3). Trimble also teaches topical vaginal insert administration of artesunate as an advantageous strategy to avoid surgery (see Trimble at p. 193 left col. ¶2).
The prior art differs from instant claims as follows: While Trimble teaches artesunate for treating HPV-induced precancerous conditions, Trimble does not teach in combination with an HDAC inhibitor or synergy.
However,
Regarding claim 1 and synergy with and HDAC inhibitor, Chen teaches that artemisinin and its derivatives exhibit synergy in combination with HDAC inhibitors for treating tumors (see Chen at Title).
Regarding claims 1, 5-8 and administering an HDAC inhibitor such as panobinostat or vorinostat to treat HPV-induced condition or claim 14 and a pharmaceutical composition comprising panobinostat or vorinostat, Banerjee teaches vorinostat abrogates viral DNA amplification and inhibited host DNA replication, leading to apoptosis in HPV-infected differentiated cells and spared uninfected tissue (see Banerjee at Abstract), and belinostat and panobinostat also inhibited DNA amplification and caused apoptosis (see id). Banerjee teaches belinostat and Panobinostat are HDAC inhibitors approved by the FDA for clinical applications (see Banerjee at p. E11145 left col. ¶3).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.06(I), "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The prior art teaches a topical formulation of artesunate for treating an HPV-induced precancerous condition such as cervical dysplasia (as taught by Trimble), and HDAC inhibitors panobinostat, vorinostat, and belinostat for treating HPV-infected cells (as taught by Banerjee). It would have been obvious to combine artesunate with panobinostat, vorinostat, or belinostat for treating an HPV-induced condition because the prior art teaches the components are known treatments for HPV or HPV-induced conditions, which would be relevant for treating a patient with an HPV-induced condition. An artisan would readily appreciate that such compositions could be manufactured and separated into dosage forms for individual administrations (e.g. kits) (see MPEP § 2143(I)(G)).
In addition, the prior art teaches artemisinin derivatives when used in combination with HDAC inhibitors offer synergy against tumors, therefore a composition comprising artesunate (an artemisinin derivative) in combination with an HDAC inhibitor would be an expected synergistic combination.
Furthermore, it is well-within the ordinary skill in art to combine compositions to form a third for the same purpose as taught by the prior art (treating a subject with an HPV-induced condition).
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Trimble in view of Chen, Banerjee, as evidenced by CAP as applied to claims 1-12, 14-15 above and in further view of Bubna5.
Recall Trimble teaches artesunate has cytotoxic effects on human solid tumors with clinical trials for the systemic oral and intravenous administration routes (see Trimble at p. 189 left col. ¶3). Trimble also teaches topical vaginal insert administration of artesunate as an advantageous strategy to avoid surgery (see Trimble at p. 193 left col. ¶2).
The prior art differs from instant claims as follows: While Trimble, Chen, Banerhee, and CAP teach a synergistic combination of artemisinin-related compounds for treating an HPV-induced precancerous or cancerous condition, they do not specify administration route of HDAC inhibitors.
However,
Babna teaches HDAC inhibitor vorinostat has been approved at 400 mg oral dosage (see Babna at p. 420 right col. “Dosing”).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to one skilled in the art to administer the artemisinin-related compound component, such as artesunate, intravaginally and an HDAC inhibitor component, such as vorinostat, orally because the prior art teaches artesunate exhibits adverse effects when administered systemically (e.g. orally) (as taught by Trimble), and that vorinostat is approved as an oral dosage (as taught by Babna).
Furthermore, it is well-within the skill of the art to administer known components according to known suitable administration routes.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
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.
I. NSDP Rejections US’024
Claims 1-12, 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,128,024 B26 in view of Chen, Banerjee, Trimble, and Babna.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding instant claims 1-12, 14, US’024 claims a method of treating HPV-induced pre-malignant lesion at a genital or anal site in a subject comprising administering a therapeutically effective amount of an artemisinin-related compound (artemisinin, dihydroartemesinine, artemether, arteether, artesunate, artelinic acid, or dihydroartemisinin propyl carbonate, US’024 claims 2-3) (US’024 claim 1) which may be administered topically (US’024 claims 4-5), and may be administered with an anti-viral or anti-cancer agent (US’024 claims 13-14).
Regarding instant claim 10, US’024 claims identifying the subject with an HPV-induced lesion at a genital or anal site (US’024 claim 10).
Regarding instant claim 15 and administration, US’024 claims a method of administering the artemisinin-related compound by topical administration (US’024 claim 5).
The instant claims differ from the patent claims as follows: While US’024 claims administering artemisinin-derived compounds to treat an HPV-induced precancerous condition in a combination therapy, US’024 does not specify the second agent is an HDAC inhibitor, the combination to be synergistic, or separate administration routes.
However,
Regarding instant claim 1 and synergy, Chen teaches that artemisinin and its derivatives exhibit synergy in combination with HDAC inhibitors (see Chen at Abstract).
Regarding instant claims 16-17 and administration routes, Trimble teaches artesunate has cytotoxic effects on human solid tumors with clinical trials for the systemic oral and intravenous administration routes (see Trimble at p. 189 left col. ¶3). Trimble also teaches topical vaginal insert administration of artesunate as an advantageous strategy to avoid surgery (see Trimble at p. 193 left col. ¶2). Babna teaches HDAC inhibitor vorinostat has been approved at 400 mg oral dosage (see Babna at p. 420 right col. “Dosing”).
Regarding US’024 anti-viral or anti-cancer agents vs instant HDAC inhibitors, Banerjee teaches vorinostat abrogates viral DNA amplification and inhibited host DNA replication, leading to apoptosis in HPV-infected differentiated cells and spared uninfected tissue (see Banerjee at Abstract), and belinostat and panobinostat also inhibited DNA amplification and caused apoptosis (see id). Banerjee thus teaches vorinostat, belinostat, and panobinostat are anti-viral towards HPV. In addition, Banerjee teaches HDAC inhibitors such as vorinostat are anti-cancerous and used as chemotherapy agents (see Banerjee at p. e11139 left col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior patent for at least the following reason(s):
The US’024 claim limitations of administering an anti-viral or anti-cancer agent reads upon the instant combination with HDAC inhibitors as taught by Banerjee. The claims are thus drawn to an overlapping scope of administering an artemisinin-derived compound and an HDAC-inhibitor to treat an HPV-induced pre-cancerous lesion. The prior art teaches artemisinin derivatives when used in combination with HDAC inhibitors offer synergy, therefore a composition comprising artesunate (an artemisinin derivative) in combination with an HDAC inhibitor would be an expected synergistic combination.
In addition, it would have been obvious to one skilled in the art to administer the artemisinin-related compound component, such as artesunate, intravaginally and an HDAC inhibitor component, such as vorinostat, orally because the prior art teaches artesunate exhibits adverse effects when administered systemically (e.g. orally) (as taught by Trimble), and that vorinostat is approved as an oral dosage (as taught by Babna).
Therefore, the claims are not patentably distinct.
II. NSDP Rejections US’491
Claims 1-12, 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 7,989,491 B27 in view of Chen and Banerjee.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding instant claims 1-12, 14-15, US’491 claims treating an HPV-induced condition such as cervical dysplasia or cervical cancer comprising identifying a subject with cervical dysplasia or cervical cancer and administering a therapeutically effective amount of an artemisinin-related compound (artemesinin, dihydroartemesinin, artemether, arteether, artesunate, artelinic acid, see also US’491 claims 2-3, 6-7) via oral, topical (see also US’491 claims 4-5), parenteral, intra-vaginal, rectal, systemic, intramuscular or intravenous administration (US’491 claim 1). US’491 claims further administering an antiviral (US’491 claims 8-9) or an anti-cancer agent (US’491 claims 10-11).
The instant claims differ from the patent claims as follows: While US’491 claims administering artemisinin-derived compounds to treat cervical dysplasia in a combination therapy, US’491 does not specify the second agent is an HDAC inhibitor or differing administration routes.
However,
Regarding synergy, Chen teaches that artemisinin and its derivatives exhibit synergy in combination with HDAC inhibitors (see Chen at Abstract).
Regarding instant claims 16-17 and administration routes, Trimble teaches artesunate has cytotoxic effects on human solid tumors with clinical trials for the systemic oral and intravenous administration routes (see Trimble at p. 189 left col. ¶3). Trimble also teaches topical vaginal insert administration of artesunate as an advantageous strategy to avoid surgery (see Trimble at p. 193 left col. ¶2). Babna teaches HDAC inhibitor vorinostat has been approved at 400 mg oral dosage (see Babna at p. 420 right col. “Dosing”).
Regarding US’491 anti-viral or anti-cancer agents vs instant HDAC inhibitors, Banerjee teaches vorinostat abrogates viral DNA amplification and inhibited host DNA replication, leading to apoptosis in HPV-infected differentiated cells and spared uninfected tissue (see Banerjee at Abstract), and belinostat and panobinostat also inhibited DNA amplification and caused apoptosis (see id). Banerjee thus teaches vorinostat, belinostat, and panobinostat are anti-viral towards HPV. In addition, Banerjee teaches HDAC inhibitors such as vorinostat are anti-cancerous and used as chemotherapy agents (see Banerjee at p. e11139 left col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior patent for at least the following reason(s):
The US’491 claim limitations of administering an anti-viral or anti-cancer agent reads upon the instant combination with HDAC inhibitors as taught by Banerjee. The claims are thus drawn to an overlapping scope of administering an artemisinin-derived compound and an HDAC-inhibitor to treat an HPV-induced pre-cancerous lesion. The prior art teaches artemisinin derivatives when used in combination with HDAC inhibitors offer synergy (as taught by Chen), therefore a composition comprising artesunate (an artemisinin derivative) in combination with an HDAC inhibitor would be an expected synergistic combination.
In addition, it would have been obvious to one skilled in the art to administer the artemisinin-related compound component, such as artesunate, intravaginally and an HDAC inhibitor component, such as vorinostat, orally because the prior art teaches artesunate exhibits adverse effects when administered systemically (e.g. orally) (as taught by Trimble), and that vorinostat is approved as an oral dosage (as taught by Babna).
Therefore, the claims are not patentably distinct.
III. NSDP Rejections US’787
Claim 1, 4-12, 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 8,940,787 B28 in view of Chen and Banerjee.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding claims 1, 4-12, 14-15, US’787 claims a method of treating HPV-induced anal cancer comprising identifying a subject, and administering an artemisinin-related compound (asrtemisinin, dihydroartemisinin, artemether, arteether, artesunate, artelinic acid, dihydroartemisinin propyl carbonate, see also US’787 claims 2-3) via oral, topical, systemic, intramuscular, or intravenous administration (US’787 claim 1). US’787 further claims administering with a carrier (US’787 claim 4), an anti-viral agent (US’787 claims 5-6) or an anti-cancer agent (US’787 claims 7-8).
The instant claims differ from the patent claims as follows: While US’787 claims administering artemisinin-derived compounds to treat HPV-induced anal cancer in a combination therapy, US’787 does not specify the second agent is an HDAC inhibitor, the combination is synergistic, or differing administration routes.
However,
Regarding instant claim 1 and synergy, Chen teaches that artemisinin and its derivatives exhibit synergy in combination with HDAC inhibitors (see Chen at Abstract).
Regarding instant claims 16-17 and administration routes, Trimble teaches artesunate has cytotoxic effects on human solid tumors with clinical trials for the systemic oral and intravenous administration routes (see Trimble at p. 189 left col. ¶3). Trimble also teaches topical vaginal insert administration of artesunate as an advantageous strategy to avoid surgery (see Trimble at p. 193 left col. ¶2). Babna teaches HDAC inhibitor vorinostat has been approved at 400 mg oral dosage (see Babna at p. 420 right col. “Dosing”).
Regarding US’787 anti-viral or anti-cancer agents vs instant HDAC inhibitors, Banerjee teaches vorinostat abrogates viral DNA amplification and inhibited host DNA replication, leading to apoptosis in HPV-infected differentiated cells and spared uninfected tissue (see Banerjee at Abstract), and belinostat and panobinostat also inhibited DNA amplification and caused apoptosis (see id). Banerjee thus teaches vorinostat, belinostat, and panobinostat are anti-viral towards HPV. In addition, Banerjee teaches HDAC inhibitors such as vorinostat are anti-cancerous and used as chemotherapy agents (see Banerjee at p. e11139 left col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior patent for at least the following reason(s):
Regarding instant claim 1 and synergy, the prior art teaches artemisinin derivatives when used in combination with HDAC inhibitors offer synergy (as taught by Chen), therefore a composition comprising artesunate (an artemisinin derivative) in combination with an HDAC inhibitor would be an expected synergistic combination.
Regarding US’787 and administering a carrier, it would be obvious to an artisan to formulate with a carrier depending on the administration route in order to improve bioavailability.
Regarding HDAC inhibitors, the US’787 claim limitations of administering an anti-viral or anti-cancer agent reads upon the instant combination with HDAC inhibitors as taught by Banerjee. The claims are thus drawn to an overlapping scope of administering an artemisinin-derived compound and an HDAC-inhibitor to treat an HPV-induced anal cancer.
Regarding instant claims 16-17 and administration, it would have been obvious to one skilled in the art to administer the artemisinin-related compound component, such as artesunate, intravaginally and an HDAC inhibitor component, such as vorinostat, orally because the prior art teaches artesunate exhibits adverse effects when administered systemically (e.g. orally) (as taught by Trimble), and that vorinostat is approved as an oral dosage (as taught by Babna).
Therefore, the claims are not patentably distinct.
Conclusion
Claims 1-12, 14-17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Trimble et al., “A First-In-Human Proof-of-Concept Trial of Intravaginal Artesunate to Treat Cervical Intraepithelial Neoplasia 2/3 (CIN2/3),” Gynecologic Oncology, 2020, 157, 1, 188-194. DOI: 10.1016/j.ygyno.2019.12.035. Published Online January 28, 2020. Cite No. 39 in the IDS filed 12/19/23. Hereinafter Trimble.
2 Chen et. al. "Synergistic Antitumor Activity of Artesunate and HDAC inhibitors Through Elevating Heme Synthesis Via Synergistic Upregulation of ALAS1 Expression", Acta Pharmaceutica Sinica B, 2019, 9, 5, p. 937-951. Cite No. 1 in the IDS filed 3/21/24. Hereinafter Chen.
3 Banerjee et. al. "Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification" Proc Natl Acad Sci USA, 2018, 115, 47, e11138-e11147. DOI: 10.1073/pnas.1801156115. Hereinafter Banerjee.
4 Cervical Condition. College of American Pathologists, Wayback Machine Archive July 27, 2015. Hereinafter CAP.
5 Bubna, A. “Vorinostat—An Overview” Indian Journal of Dermatology 2015, 60, 4, 419-422. DOI: 10.4103/0019-5154.160511
6 Patented October 29, 2024, filed October 16, 2020. Corresponding to Application No. 17/072,726 and Cite No. 3 in the IDS filed 10/18/22. Hereinafter US’024.
7 Patented August 2, 2011. Hereinafter US’491.
8 Patented January 27, 2015. Corresponding to Application No. 13/777,244. Hereinafter US’787.