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 Amendments
Applicant’s amendments to the claims of April 13, 2026, in response to the Office Action of November 12, 2025, are acknowledged.
Response to Arguments
Applicant has amended the claims to require treating a HPV positive cancer. The examiner withdraws the anticipatory rejections in light of this amendments. However, the examiner notes the following:
Okunade et al., “Human papillomavirus and cervical cancer,” September 10, 2019, pages 602-608, Abstract, teaches: “About 99.7% of cervical cancer cases are caused by persistent genital high-risk human papillomavirus (HPV) infection.”
Saraiya et al., “US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines,” JNCI Natl Cancer Inst (2015) 107(6), teaches HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75% of vaginal, 70.1% of oropharyngeal, and 98.8% of cervical cancer in situ (CCIS). Thus, when prior art teaches treating any of these cancers with a claimed agent, there is no reason to expect that such teachings are impliedly and tacitly excluding the most prevalent subjects because they are also positive for HPV. This is the typical subject having claimed cancers.
With regard to new claims 19 and 20, the examiner notes that Hsieh (of record) includes medications including cetuximab, gefitinib, and other EGFR inhibitors. See par. 35. This is in addition to erlotinib and others. See par. 33. Even further, examples and claims are directed to lapatinib (also an EGFR inhibitor).
As such, the claimed agents are known and taught to be administered to the claimed subject population. Further, Hatami described a synergy with the claimed agent for treating many cancers in combination with many drugs, including doxorubicin and cisplatin because gambogic acid is a chemosensitizing agent, e.g. As such, when the claimed agent is administered to the claimed subject, the same result will occur. Further, when greater than 90% of subjects with claimed forms of cancers are taught to be treated, a POSA expects that such subject is HPV positive and would not avoid treating them without explicit guidance. While the examiner cannot maintain a anticipatory rejection based on probabilities, a 103 obviousness rejection is maintained.
Status of the Claims
Claims 1-20 are pending and examined.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-20 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, claims 1 and 10 recite “an analog thereof.” The Specification provides specific examples of 8 compounds, which are analogs. However, an analog includes any compound that differs in structure by at least one atom, functional group, or moiety. This can include hundreds of combinations if not more.
The MPEP § 2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plan for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. Although the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus, if the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office (PTO) Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5, 2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention" Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106). Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP §2163. However, if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP §2163.
Level of skill and knowledge in the art: The level of skill in the art is high.
Partial structure: As to the claimed ‘an analog thereof ' of gambogic acid and no specific examples other than the tested 8 specific compounds are given that would demonstrate possession of or put the public in possession of the claimed analogs.
Physical and/or chemical properties/Functional characteristics: The compounds claimed and “an analog thereof,” are compounds which are allegedly useful for treating specific types of cancers. With regard to an analog thereof, Applicant has not set forth compounds or substituents in the specification which Applicant considers analogs thereof with the exception of 8 specific compounds. Although the art recognizes the above definitions the terms are not explicitly defined by the specification in such a way as to demonstrate that the inventor had possession of the claimed ‘analogs.'
Predictability of the Art: It is generally accepted in the art that formation of a particular ‘derivatives' for a given compound or series of compounds is unpredictable. As stated by Dorwald (Side Reactions in Organic Synthesis: A Guide to Successful Synthesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2005, Preface): “Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why. Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work.
Method of making the claimed invention: Although the Specification provides a method for making the elected species, no method for making the analogs encompassed by the claims has been disclosed. Only a limited number of compounds are shown to be synthesized by the instant Specification.
Summary: In the instant case, Applicant has not disclosed the structure, formula, chemical name, or physical properties of the numerous potential analogs of gambogic acid. Although some functional characteristics are disclosed or would be known to a person of ordinary skill in the art, in the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed ‘analogs' in the instant application.
However, the MPEP states that written description for a genus (for example, the claimed ‘prodrugs,’ ‘analogs’ or ‘derivatives' of the elected compound species) can be achieved by a representative number of species within a broad generic. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims: the possible structural variations are limitless to any analog of gambogic acid. In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. While having written description of the elected compound and compounds identified in the Specification tables and/or examples, the Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims such as, for example, ‘analogs' of GA.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
To overcome this rejection, Applicant can merely remove the phrase “analogs” from the claims or limit the analogs to those species described in the Specification.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hatami et al., “Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics,” Biochim Biophys Acta Rev Cancer. 2020 August; 1874(1):188381, as evidenced by Wang et al., “Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. intermediacy of H(2)O(2)- and p53-dependent pathways. J Biol Chem. 2004 Jun 11;279(24):25535-4, in view of Han et al., (US2007/0149610), in view of Hsieh, (US2015/0224334), and in view of Reed et al., (US20090163577), as evidenced by Okunade et al., “Human papillomavirus and cervical cancer,” September 10, 2019, pages 602-608, Abstract, and as evidenced by Saraiya et al., “US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines,” JNCI Natl Cancer Inst (2015) 107(6).
The examiner notes that prior art teaches GA and 30-hydroxyGA. However, the instant claims include GA or a derivative, as well as 30-hydroxyGA or a derivative. The examiner interprets GA to be inclusive of a derivative of 30-hydroxyGA. While the examiner does not rely on this interpretation solely to address the claims, such interpretation can impact how each of the cited references addresses the claims. Applicant can remove the phrase “derivative thereof” from the claims to require either GA or 30-hydroxyGA to be administered.
Hatami teaches gambogic acid (GA) can have a significant anticancer effect on various types of cancers, including head and neck and cervical cancers, among a variety of others. See p3, 1st full par. Further, GA has efficacy against oral squamous cell carcinoma cell lines. See p11, last par. It is known to have a chemo-sensitization effect and synergistic effect in cancer cells when used with drugs including doxorubicin and cisplatin, among others. See p12, 3rd full par. Further, GA is a primary adjuvant for many cancers and GA is also involved in sensitization for radiation treatments. A combination of GA and radiation in nasopharyngeal carcinomas cells promotes apoptosis dues to G2/M-phase arrest and HIF-1alpha/cyclin B1/cdc2 pathway. See p13-14, bridging par. Hatami teaches that GA is synergistic actions of GA is considered to increase the intracellular concentration of chemotherapeutic agents in cancers cells and at the tumor site and this was noticed for doxorubicin, cisplatin, and others. Figure 4 shows that gambogic acid is used to treat head and neck cancer, cervical cancer, and colorectal cancers. Table 3 shows a sensitization/synergy with many drugs for a variety of cancers when those drugs work through various mechanisms of actions. Those drugs include doxorubicin and cisplatin for breast, ovarian, and NSCLC. Other agents synergized with GA to treat colorectal cancer and others. As evidenced by Wang, doxorubicin is an apoptosis inducing chemotherapeutic agent. See Title.
Han teaches the following compounds have anticancer effects including GA and 30-hydroxygambogic acid. See par. 7. These drugs work because they are not substrates of MDR transporter. See Abstract.
Hsieh teaches methods for treating cancer growth with an NPM inhibitor, which is GA. See prior art claims 3 and 15. Further, the cancers to be treated include cervical, uterus, and other cancers. See prior art claim 26. Further, the method includes using a conventional chemotherapeutic agent in additional to an NPM inhibitor. See prior art claim 20. Further, the combination with a convention agent includes radiation therapy. See par. 25. The conventional anti-cancer agent can be cisplatin, doxorubicin, or cetuximab. See par.’s 27, 29, and 35. The use of radiation the NMP inhibition prevents resistance to cell death. See par. 49. A preferred cancer to be treated is cervical cancer. See par. 51. A POSA would immediately envisage treatment with GA before and/or after radiation therapy and potentially both.
Reed teaches a method of treating cancer by administering a composition comprising a gambogic acid or a derivative thereof. See prior art claim 24. Further, the method includes treating cervical cancer and head and neck cancer. See prior art claim 25. This includes squamous cell carcinoma of the head and neck. See par. 45.
Evidentiary references shown below show that the typical subject with the claimed forms of cancers are HPV positive.
Okunade teaches: “About 99.7% of cervical cancer cases are caused by persistent genital high-risk human papillomavirus (HPV) infection.”
Saraiya teaches HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75% of vaginal, 70.1% of oropharyngeal, and 98.8% of cervical cancer in situ (CCIS). Thus, when prior art teaches treating any of these cancers with a claimed agent, there is no reason to expect that such teachings are impliedly and tacitly excluding an the above percentages of subjects because they are also positive for HPV. This is the typical subject with the claimed cancers.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of the cited prior art. One would be motivated to do so because gambogic acid is taught to treat the claimed cancers and is taught to be used in combination with radiation and chemotherapeutic agents, including doxorubicin, cisplatin, and cetuximab. Further, GA is taught to work with chemotherapeutic agents as well as radiation by increasing the concentration of these drugs in a subject as well as preventing resistance mechanisms in tumors. It is noted that GA and OH-GA are almost structurally identical and each taught to be used as an anticancer agent. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See M.P.E.P. § 2144.09. Moreover, “The presumption of obviousness based on a reference disclosing structurally similar compounds may be overcome where there is evidence showing there is no reasonable expectation of similar properties in structurally similar compounds.” In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Even further, the claimed cancers are known to be HPV positive including multiple cancers in which greater than 90% of subjects are HPV positive and greater than 70% in others. Thus, a POSA would understand that when prior art teaches treating these specific types of cancers with specific agents that such prior art is including subjects that are also HPV positive, absent evidence to the contrary.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
