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 1-20 are pending. Claims 1-6 and 11-20 are rejected. Claims 7-10 are objected to.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 11/27/2023 was considered by the Examiner.
Objection to Specification
The specification amendment filed on 11/27/2023 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. Specifically, the following new phrase is not supported by the application (as filed on 5/26/2022): “the disclosures of which are incorporated herein by reference in their entireties.” (see para. [0001]). 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. See MPEP 211.02 and MPEP 201.06(c)(IV). PCT Rule 20.6, Rule 20.7 and Rule 4.18 are directed specifically to 371 applications. This rejection may be overcome by deleting the aforementioned phrase.
Claim Objections
Claim 1 is objected to because of the following informality:
P. 2, line 17: insert a comma between “C1-6 hydroxyalkyl” and “-C(O)NRFRG”.
Claim 2 is objected to because of the following informality:
“Claim 1” should read “claim 1”.
Claim 3 is objected to because of the following informality:
“Claim 1” should read “claim 1”.
Claim 4 is objected to because of the following informality:
“Claim 1” should read “claim 1”.
Claim 5 is objected to because of the following informality:
“Claim 1” should read “claim 1”.
Claim 6 is objected to because of the following informalities:
“Claim 5” should read “claim 5”;
Claim needs to end in a period.
Claim 7 is objected to because of the following informality:
In line 1, “Claim 1” should read “claim 1”.
Claim 8 is objected to because of the following informality:
In line 1, “Claim 7” should read “claim 7”.
Claim 9 is objected to because of the following informality:
In line 1, “Claim 1” should read “claim 1”.
Claim 10 is objected to because of the following informality:
In line 1, “Claim 9” should read “claim 9”.
Claim 11 is objected to because of the following informality:
In line 1, “Claim 1” should read “claim 1”.
Claim 12 is objected to because of the following informality:
In line 1, “Claim 1” should read “claim 1”.
Claim 13 is objected to because of the following informality:
In line 1, “Claim 1” should read “claim 1”.
Claim 14 is objected to because of the following informality:
In line 1, “Claim 13” should read “claim 13”.
Claim 15 is objected to because of the following informality:
“Claim 14” should read “claim 14”.
Claim 16 is objected to because of the following informality:
“Claim 14” should read “claim 14”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 11 is 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. Claim 11 depends from claim 1 and fails to limit the definition of the “X” variable. 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.
Claim 14 is 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. Claim 14 depends from claim 13 and recites the following as possibilities of RA that do not correctly depend: methoxy, trifluoromethoxy, and hydroxyethyl. The following is from paragraph [0046] from the instant specification:
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(which embraces the C1-C3 alkyl of instant claim 13). The definition from the specification shown supra does not indicate that simply “alkyl” (or C1-C3 alkyl from instant claim 13) may be hydroxy substituted or an alkoxy. 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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 and 11-20 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.
On p. 2 of claim 1, particularly the R3 definition with “(A)” and “(B)”, there are multiple “or” connections within each “(A)” and “(B)”. It is unclear if variables within these definitions are all intended to be substituted on the C3-C8 cycloalkyl and 3-10 membered heterocyclyl for “(A)” and “(B)”, respectively, or if they are intended to be options in addition to C3-C8 cycloalkyl and 3-10 membered heterocyclyl for “(A)” and “(B)”, respectively. If Applicant intended for all those variables separated by “or” to be substituents on C3-C8 cycloalkyl and 3-10 membered heterocyclyl for “(A)” and “(B)”, respectively, Examiner recommends maintaining one “or” at the end of each list. Claims 2-6, 11-16 and 18-20 are rejected for depending on claim 1 and failing to remedy this deficiency.
Claim 17 is rejected because it refers to “Examples 1-182” of the instant specification. A claim should particularly point out and distinctly claim the subject matter which the applicant regards as his invention and, under modern claim practice, stand alone to define the invention. MPEP 2173.05(s) states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)”. Examiner recommends placing the structures or names of all Examples 1-182 within the body of claim 17 to overcome this rejection. In the interest of compact prosecution, Examiner has examined the compounds of Examples 1-182 from the instant specification.
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.
The rejection of claim 19 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inhibiting SOS1:KRAS interaction, does not reasonably provide enablement for treatment of cancer in general, or treatment of the cancers recited apart from the aforementioned indications is maintained. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with claim 19.
Nature of the invention:
The invention is drawn to a method of treating cancer comprising administration of a compound of formula (I):
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, as recited in instant claim 1.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to administration of any of the numerous compounds encompassed by a formula (I) as instantly recited to treat cancer.
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.
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, 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:
Beginning on p. 311, a biological FRET assay is demonstrated to inhibit the SOS1:KRAS interaction.
Beginning on p. 316, a biological SPR (surface plasmon resonance) SOS1 binding assay is demonstrated.
No examples have been provided that would enable the instantly disclosed compounds for treating cancer generally, as claimed in instant claim 19.
Quantity of experimentation needed to use the invention
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 be able to investigate the efficacy of the disclosed compounds in the treatment of cancer generally, but would also need to evaluate the disclosed compounds, with no assurance of success.
The Applicant has not sufficiently disclosed examples demonstrating the efficacy of the instantly claimed compounds in treating cancer generally. The utility thereof would not have been readily recognized by a person having ordinary skill in the art at the time of filing, as distinct cancers have mutually exclusive etiologies. The examples disclosed in the application are not sufficient to overcome the unpredictability of treating cancer generally.
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.
Genentech Inc. V Novo Nordisk A/S (CAFC) 42 USPQ 2d 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 determine the efficacy of disclosed compounds in treating cancer, with no assurance of success.
Closest Prior Art
The closest prior art to claims 1-20 is US10829487. US10829487 teaches the following compound as an inhibitor of SOS1 (arrow added by Examiner):
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(see abstract and column 247). The prior art compound differs in multiple location than an instant compound of Formula (I), including that at the location of the added arrow. For example, the left-hand ring (by the added arrow) of the prior art does not require an oxo group substituent and the nitrogens are connected differently (not adjacent). Therefore, the prior art does not provide motivation for nor render obvious the instant claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEGHAN C HEASLEY whose telephone number is (571)270-0785. The examiner can normally be reached Monday - Friday 8:30-4:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at 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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/MEGHAN C HEASLEY/Examiner, Art Unit 1626