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 Claims
Claims 1-20 are pending in the instant application.
Domestic Benefit
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/069,981, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Regarding Claims 1-20, insufficient support is provided in the prior-filed provisional application ‘981, as no working examples demonstrating the efficacy of administering selpercatinib and Osimertinib to treat a patient with an EGFR-associated cancer and a RET-associated cancer have been provided. The prior-filed provisional application describes a number of embodiments of the instant invention, but enabling data to support the claim of treating a patient with an EGFR-associated cancer and a RET-associated cancer have not been provided. Therefore, no support is provided in the provisional application ‘981 to enable treating an EGFR-associated cancer and a RET-associated cancer.
U.S. Patent Application No. 18/041,617 is a national stage entry of PCT/US2021/047496, international filing date of August 25th, 2021.
Information Disclosure Statement
The Information Disclosure Statement filed on February 14th, 2023 has been fully considered, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 uses the acronyms “EGFR” and “RET” without previously defining these acronyms. The Examiner has interpreted “EGFR” to mean “epidermal growth factor receptor”, as stated at Page 9 of the instant specification, and “RET” to mean “Rearranged during Transfection”, as stated at Page 1 of the instant specification.
Appropriate correction is required.
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(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of treating a patient with an EGFR-associated cancer and a RET-associated cancer comprising administering selpercatinib and Osimertinib.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to the treatment of any cancer classified as EGFR-associated and RET-associated. This includes a myriad of known cancers with distinct etiologies, and could include cancers either known presently in the art, later classified as EGFR-associated and RET-associated, or cancers not presently known, but later discovered and classified as EGFR-associated and RET-associated.
State of the prior art and predictability in the art:
No compound has ever been found to treat cancers of all types generally. Since this assertion is contrary to what is known in medicine, proof must be provided that this revolutionary assertion has merits. The existence of such a “silver bullet” is contrary to our present understanding of oncology. The state of the art is not indicative of any pharmaceutical agents that are useful in the treatment of cancer generally. At Page 1004, Cecil Textbook of Medicine states that “each specific type has unique biologic and clinical features that must be appreciated for proper diagnosis, treatment and study”. Different types of cancers affect different organs and have different methods of growth and harm to the body. Also see In re Buting, 163 USPQ 689 (CCPA 1969), wherein ‘evidence involving a single compound and two types of cancer, was held insufficient to establish the utility of the claims directed to disparate types of cancers’. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally.
A similar statement appears at In re Application of Hozumi et. al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. This is because it is now understood that there is no “master switch” for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body’s cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environmental factors.
Similarly, In re Novak, 134 USPQ 335, 337-338 says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case for a compound that treats all types of cancer. Likewise, In re Cartright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Moreover, even if Applicant’s assertion that cancer in general could be treated with these compounds were plausible -- which it is not --, that “plausible” would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.
Recently, Wu et. al. (“Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA- approved novel therapeutic drugs for solid tumors from 1991 to 2021; Journal of Hematology & Oncology, 15, 143, 2022; hereinafter referred to as Wu), at the Abstract, discloses that between 1991 and 2021 there have been 228 new cancer drugs approved by the U.S. Food and Drug Administration of which 120 of these are drawn to the treatment of solid tumors alone. At Page 5, Table 1 Wu teaches that there are 21 different approved drugs for treating lung cancers, some of which have cellular targets. At Page 10, Table 2, Wu teaches breast cancer has 22 different drugs that have varied cellular targets and are indicated for different types of breast cancer. At Page 17, Table 4, Wu teaches there are 17 different drugs available to treat different forms of gastrointestinal cancers. At Page 38, Figure 12, Wu summarizes the protein structure of some cellular targets and the binding site of their respective drugs. Taken together, Wu teaches that no single therapeutic has ever been identified as a treatment for all forms of cancer; and closer examination of Figure 12 provides a logical explanation. As highlighted in Figure 12, molecular protein targets implicated in different cancers (e.g. EGFR for lung cancer in Table 1, VEGFR2 for gastric cancer in Table 4) have different three-dimensional protein structures, different active sites, and therefore require different drugs with the right shape and chemical groups in order to bind the target active site and have an effect in treating cancer. In other words, there is no one size fits all approach to treating cancer simply for the reason that no single molecule will have the shape and chemical functional groups necessary to bind and modulate all modular targets of cancer, all of which have varied shapes. It is commonly known in the pharmaceutical arts that shape dictates function wherein drugs which have a shape complimentary to the protein target will bind and have an effect (this is often referred to simplistically as a “Lock and Key” model). Given the varied shape of protein targets in cancer (e.g. EGFR and VEGFR2), it is pure fantasy to speculate that a single drug with a single three dimensional shape will bind all protein targets implicated in cancer therapy and have an effect in treating all forms of the disease. As such, at present the “silver bullet” drug therapy to treat all forms of cancer is elusive and such a therapy is not recognized in the art where the reality is that different forms of cancer require different drug therapies.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
No examples are instantly disclosed demonstrating the efficacy of the claimed invention.
Throughout the specification, Applicant has described various embodiments of the invention including dosage amounts and routes of administration of selpercatinib and Osimertinib.
Additionally, Applicant provides at Table 1, beginning at Page 18 of the instant specification, a description of exemplary RET fusion partners and the associated cancers thereof.
At Table 2, beginning at Page 21 of the instant application, Applicant has disclosed the amino acid positions at which a RET point mutation may occur.
At Page 28, Table 3, Applicant has disclosed mutations associated with RET inhibitor resistance.
At Table 4, beginning at Page 27, Applicant has provided additional mutations associated with RET inhibitor resistance.
No data have been provided however, demonstrating that a single embodiment of the invention has been administered to a patient, nor has any data been provided demonstrating the efficacy of doing so. In view of this, a person having ordinary skill in the art would not readily understand the motivation to select one embodiment of the instantly claimed invention over another, nor would a person having ordinary skill in the art readily understand the or be able to reasonably predict the outcome of deploying such an embodiment.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. A person having ordinary skill in the art would need not only to identify and/or develop metrics to determine the efficacy of the claimed method of treating an EFGR-associated and RET-associated cancer, but also need to evaluate the method against these metrics with no assurance of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
The specification fails to provide enough support for the instantly claimed method of treating an EGFR-associated and RET-associated cancer.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to practice the claimed method of treating an EGFR-associated and RET-associated cancer, with no assurance of success.
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, 3-4, 8, 10-14, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hata et. al. (WO 2020/033838 A2; cited on Applicant’s Information Disclosure Statement filed February 14th, 2023; hereinafter referred to as Hata).
Regarding Claim 1, at Page 18, Paragraph 66, Hata teaches selpercatinib is referred to as LOXO-292.
At Page 4, Paragraph 17, Hata teaches a method for treating and EGFR-mutant cancer comprising administration of at least one RET inhibitor and at least one EGFR inhibitor. Further, Hata teaches the RET inhibitor is chosen from a group including LOXO-292. Further, at Page 5, Lines 7-8, Hata teaches the EGFR inhibitor is chosen from Osimertinib and pharmaceutically acceptable salts thereof.
The instant specification defines “RET-associated cancer” at Page 10, Lines 18-21, as cancers associated with or having a dysregulation of a RET gene, a RET kinase, or expression or activity or level of any of the same.
Hata teaches at Page 5, Lines 13-14 that the EGFR-mutant cancer is characterized by at least one RET-fusion, defined at Page 11, Paragraph 35 as a gene rearrangement creating a fusion juxtaposing the RET kinase domain and a dimerization domain of another protein, creating a constitutively activated dimer which drives tumorigenesis.
Taken together, Hata teaches a method of treating an EGFR and RET_associated cancer comprising administration of selpercatinib and Osimertinib, and therefore anticipates instant Claim 1.
Regarding Claims 3-4, Hate teaches at Pages 17, Paragraphs 64-65, that the RET protein may have a mutation at the 634, 804, or 918 residues.
Regarding Claim 8, Hata teaches at Page 31, Example 4, that acquired resistance resulting from CCDC6-RET expression can be overcome by administering an EGFR inhibitor with osimertinib.
Regarding Claims 10 and 12-13, Hata teaches at Page 16, Paragraph 60 administration of Osimertinib mesylate with a weight equivalent of 40 or 80 mg.
Regarding Claim 11, at Page 3, Paragraph 13, Hata teaches oral administration of 80 mg of Osimertinib or the weight equivalent of a pharmaceutically acceptable salt thereof.
Regarding Claim 14, Hata teaches at Page 18, Paragraph 66, administration of LOXO-292 as the free base.
Regarding Claim 20, at Page 5, Lines 19-20 Hata teaches the aforementioned method is suitable for treating lung cancer. Further, at Page 16, Paragraph 55, Hata teaches the aforementioned method is suitable for treating papillary thyroid cancer.
Conclusion
Claims 1-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624