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
Response to Amendment
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/08/2026 has been entered.
Newly amended Claims 75-83, 86-88, 90-91, and 93-99 are pending in the application and examined herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
With respect to Claims 75 and those dependent thereon, applicant argues that the inhibition of viral E6 and E7 proteins by Ovatodiolide (OVT), as discovered by applicant, is surprising (Spec: Page 3, Lines 8-9). While Preethy teaches an extract containing OVT and AA overcome the effects of E6 and E7 proteins to induce cell cycle arrest (Page 32, Para 2), Paul (Biochemical Pharmacology 89 (2014) 171–184) teaches that AA is responsible for the downregulation of E6/E7 rather than OVT (Page 183):
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. Applicant’s argument is fully considered and persuasive. One of ordinary skill in the art would not have known or been able to attribute anti E6/E7 activity to OVT alone instead of AA or an extract containing AA along with OVT. Applicant’s discovery of the unpredictable capability of OVT alone overcomes the rejections issued over Preethy et al. and Lin et al.
It is noted, however, that Claims 81-82 which depend on Claim 75 require the treatment of cancer with OVT in combination with AA. Applicant’s results are not unexpected with respect to known treatment with OVT and AA because Preethy teaches such methods as explained in the previous action and below.
Regarding the 35 USC 103 rejection issued over independent Claim 83, applicant argues the unexpected result as described above as well as results drawn to increased apoptosis and caspase-3 induction by OVT as compared to AA. Applicant’s arguments are fully considered, but in this case, not persuasive. Apoptosis and caspase-3 are implicated in HPV-related neoplasms and cancers. It is unclear how caspase-3, the apoptosis mechanism, or the oncoproteins E6 and E7 are implicated in the pathology of non-cancerous genital or non-genital warts as claimed by applicant in Claim 83, which now precludes the treatment of neoplastic diseases like cancer. However, Eriksson is directed to treatment of warts with AA with no mention of OVT. In fact, Eriksson repeatedly teaches extracting AA compound in a pure form or synthesizing the compound to exclude other plant compounds present in the extract, including OVT (Page 7, Line 24-Page 8, Line 12). No other patent or non-patent art teaches the use of OVT or non-AA enriched A. malabarica extract for the treatment of HPV warts. Therefore the rejections over Claim 83 and all dependent claims are withdrawn.
Regarding applicant’s arguments that particular dosages and ratios must be explicitly taught in the cited references, the therapeutic amounts of each component are in fact taught in the prior art and the combination of elements is taught in the prior art. Further, it is noted that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II). Not only has applicant set forth a showing that any of the claimed ranges or amounts are critical, but applicant has also failed to select specific ranges to reflect “a particular weight ratio”. Instead, applicant has claimed vast ranges of different amounts and ratios; e.g., “0.001 mg/kg to about 1000 mg/kg”, “5 mg/kg to about 1000 mg/kg”, and “90:10 to 10:90”. Each of these claimed ratios span several orders of magnitude between the upper and lower bounds without a showing of criticality or unexpected results commensurate with said ranges.
Applicant also offers unexpected results in that “OVT also enhances the activity of AA…in HPV cancer cells”. However, applicant’s broad statement is not limited to any particular ratio—let alone the broad scope of ratios as claimed. Therefore, applicant’s arguments are not commensurate with the scope of the amended claims and are therefore not persuasive.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 81-82 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 81-82 depend on Claim 75 which teaches “no therapeutically effective amount of anisomelic acid…is administered”. However, Claim 81, upon which Claim 82 also depends, teaches “administering a therapeutically effective amount” of AA. The limitations conflict and the dependent claims alter the scope of Claim 75 to a mutually exclusive method.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 81 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Preethy (J Pharmacol Pharmacother. 2012 Jan-Mar;3(1):26–34., cited in 3/25/2025 IDS).
Preethy teaches “n-Hexane and chloroform extracts of A. malabarica inhibit proliferation of and induce death in HPV16-positive cervical cancer cells” (Abstract). “A. malabarica has been reported to contain secondary metabolites such as anisomelic acid [AA], [and] ovatodiolide [Ova]” (Page 27, Right Col, Para 1). Treatment is directed to human women; “Cervical cancer is the second largest cause of cancer deaths in women worldwide. Human papilloma viruses (HPVs) are the causative agents of over 99% of cervical cancers” (Page 26, Para 1).
Regarding the limitation that administering inhibits E6 and E7 expression, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Preethy teaches administration of OVT and AA, which necessarily results in the claimed inhibition. See Spec: Page 3 and Preethy: Page 32, Para 2.
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.
Claims 81-82 and 99 are rejected under 35 U.S.C. 103 as being unpatentable over Preethy (J Pharmacol Pharmacother. 2012 Jan-Mar;3(1):26–34., cited in 3/25/2025 IDS) in view of Lin (Phytomedicine 46 (2018) 93–103) and Eriksson (WO2014033366, published 3/06/2014, cited in 3/25/2025 IDS).
Preethy teaches “n-Hexane and chloroform extracts of A. malabarica inhibit proliferation of and induce death in HPV16-positive cervical cancer cells” (Abstract). “A. malabarica has been reported to contain secondary metabolites such as anisomelic acid [AA], [and] ovatodiolide [Ova]” (Page 27, Right Col, Para 1). Treatment is directed to human women; “Cervical cancer is the second largest cause of cancer deaths in women worldwide. Human papilloma viruses (HPVs) are the causative agents of over 99% of cervical cancers” (Page 26, Para 1).
Regarding the limitation that administering inhibits E6 and E7 expression, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Preethy teaches administration of OVT and AA, which necessarily results in the claimed inhibition. See Spec: Page 3 and Preethy: Page 32, Para 2.
Eriksson teaches methods of treating HPV-mediated cancers, including cervical cancer, and genital warts in mammals comprising topically administering a therapeutically effective amount of AA to said mammals (Pages 23-24; Claims 17-24). Therapeutic ranges of AA include 0.7-30mg/kg (Page 11, Lines 8-19). Lin teaches “Ova [(OVT)] effectively suppressed oral tumorigenesis and stemness properties via JAK2/STAT3 signaling. Ova may be considered for future clinical usage” (Abstract). Lin teaches the use of 3.6mg/kg OVT (Page 95, In vivo tumor xenograft; Pages 98-99). The safe and therapeutic OVT amount taught in Lin, 3.6 mg/kg, combined with the upper and lower bounds of AA amounts taught in Eriksson yield a ratio of between 10.8:90 (e.g.: 3.6/90*30=10.8) and 90:17.5, squarely within the 10:90 to 90:10 range as claimed in Claims 82 and 91. Further, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II).
Conclusion
Claims 81-82 and 99 are rejected. 75-80, 83, 86-88, 90-91, and 93-98 are allowable.
Inquiries
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627