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 .
Status of the Claims
Claims 1-18 are pending and examined.
Claim Objections
Claims 8, 9, 17 and 18 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 17 and 18 have not been further treated on the merits.
Claim Rejections - 35 USC § 112
Claims 1, 4-10, and 13-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The phrase HPV “associated cancer” is not clear as it is not clear what cancers are associated and which are not. While HPV causes claimed cancers, it is not clear is cervical cancer not caused by HPV is an HPV associated cancer, e.g. Further, if the list of cancers in claim 2 is extensive, it is not clear that claim 2 further limits claim 1.
According to Katirachi et al., “The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma,” Viruses, 2023 Feb 6; 15(2):451, “Human papillomavirus (HPV) is an important risk factor in a subset of head and neck squamous cell carcinomas (HNSCC), but the association with oral cavity squamous cell carcinomas (OCSCC) remains controversial.” Abstract.
Similarly, Ren et al., “Human papillomavirus infection increases the risk of breast carcinoma: a large-scale systemic review and meta-analysis of case-control studies,” Gland Surg 2019; 8(5):486-500, teaches clinical research both refutes and supports a relationship between breast cancer and HPV. See Abstract.
As such, the metes and bounds of the phrase HPV “associated cancer” are not clear.
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 1-18 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 “or a pharmaceutically acceptable derivative thereof.” This is defined by the instant Specification to include any: salt, pro-drug, metabolite, ester, ether, hydrate, polymorph, solvate, complex, and adduct, which are capable of providing gambogic acid. See par. 36.
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 ‘derivative' of gambogic acid and ‘derivative’ of 30-hydroxygambogic acid, no specific examples are given that would demonstrate possession of or put the public in possession of the claimed derivatives of the claimed compounds other than those described by the prior art, including: gambogic acid and 30-hydroxyepigambogic acid.
Physical and/or chemical properties/Functional characteristics: The compounds claimed and “derivatives thereof,” are compounds which are allegedly useful for treating specific types of cancers. With regard to derivatives, Applicant has not set forth compounds or substituents in the specification which Applicant considers derivatives thereof. 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 ‘derivatives' of the elected compound species.
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 derivatives 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 derivatives of compounds of Formula (I). 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 ‘derivatives' 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 ‘derivatives' of the claimed fatty acids. 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, ‘derivatives' of the claimed fatty acids.
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 “derivative thereof” from the claims or limit the derivative to a specific form.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hatami et al., “Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics,” Biochim Biophys Acta Rev Cancer. 2020 August; 1874(1):188381.
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. In particular, GA at 3 μg/mL proved to have significant inhibitory activity in HeLa cervical cancer cells. See p11, last full par.
As such, claims 1 and 2 are anticipated by Hatami.
Claims 1, 2, 4-9 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hsieh, (US2015/0224334).
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.
As such, claims 1, 2, and 4-9 are anticipated by Hsieh.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Reed et al., (US20090163577).
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.
As such, claims 1-3 are anticipated by Reed.
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 1-18 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).
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.
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).
As such, no claim is allowed.
Conclusion
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 9-5 M-F.
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