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 Application
The Office Action is in response to the application filed October 2, 2023. Amended claims 1-9 and 11-16 are being examined on the merits herein.
Objections
Structures throughout specification are grayed out and hard to read, namely pages 35-44, 69-70, and 127-140. Structures in claims 1, 2 and 4 are grayed out. Corrective action is required.
Claim 4 does not end with a period. Corrective action is required.
Claim Rejections - 35 USC § 112, first paragraph
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 11-16 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of inhibiting SHP2 activity, wherein diseases treatable by such inhibition include disorders selected from the group consisting of cancer, cardiovascular disease, immunological disorder, autoimmune disorder, fibrosis, an ocular disorder, systemic lupus erythematosus, diabetes, neutropenia and combinations thereof, comprising administering a compound or the pharmaceutically acceptable salt or stereoisomer thereof according to claim 1 to a patient in need thereof, does not reasonably provide enablement for the treatment and prevention of any disease or disorder mediated by the activity of SHP2 as recited in the instant claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification does not provide sufficient information that all the ailments in the instant claims are treatable by compounds of formula I as described in the methods claimed.
The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and nature of the invention
The breadth of the instant claims is seen to encompass methods for treating/preventing of any disease or disorder mediated by the activity of SHP2 with Formula I of the instant claims.
The claims are extremely broad. Currently, there are no known agents that treat all SHP2-meidated diseases inclusively.
The state of the prior art and level of predictability in the art
Kanumuri (Expert Opinion On Therapeutic Targets, 2022) teaches while SHP2 inhibitors have exhibited promise in preclinical trials, numerous challenges remain in translation to the clinic, including drug resistance (abstract). Furthermore, targeting SHP2 is difficult due to its structural similarity with other phosphatase family members. Apart from four proximal regions containing different residues, most of the catalytic sites between SHP1 and SHP2 are identical. The similarity between SHP1 and SHP2 resulted in the failure of first-generation SHP2 inhibitors as they lacked specificity for SHP2and caused severe side effects (page 327, column, Section 6).
Song (Acta Pharmaceutica Sinica B, 2021) describes a large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified, yet few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors(abstract). Traditional inhibitors often suffer from low cell permeability and poor oral bioavailability, thereby making them ineffective as systemic drugs (page 14).
Thus, the treatment of these disorders is highly unpredictable. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction provided by the inventor and existence of working examples
The specification does not provide guidance for the treatment and/or prevention of the scope of disorders embraced by umbrella term SHP2-meidated diseases as recited with Formula I. Applicant provides the efficacy of select compounds of Formula I in the inhibition of SHP2 activity (see Table 2).
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. In re Wright, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the Applicant's claim to the treatment/prevention. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating/preventing the embraced disorders with the claimed compound.
The level of one of ordinary skill.
The level of skill in the art is high (MD’s, PhD’s, or those with advanced degrees). As discussed above, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
The quantity of experimentation.
Considering the state of the art as discussed by the references above, particularly with regards to the alleviation of the scope of disorders recited or the prevention of the scope of disorders claimed with Formula I, the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Genentech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable." Therefore, methods of treatment and prevention of any disease or disorder mediated by the activity of SHP2 by administering Formula I of the claims is not considered to be enabled by the instant specification.
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, 15, and 16 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation R1, “optionally substituted with one or more CH3, NH2, halogen or OH and wherein R′ and R″ are each independently H or C1-6alkyl” and the claim also recites “preferably H or CH3“ which is the narrower statement of the range/limitation; R7 is selected from H, C1-3alkyl and NH2, and the claim also recites “preferably from H, CH3, and NH2“ which is the narrower statement of the range/limitation; claim 15 recites the broad recitation “at least one further therapeutic agent” and the claim also recites “preferably said at least one further therapeutic agent…”; claim 16 recites the broad recitation “at least one pharmaceutically acceptable excipient” and the claim also recites “preferably said at least one further therapeutic agent…”which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 15 (parts c, d, h, j, k) and claim 16 (parts c, d, h, j, and k) recite the phrase "such as" rendering the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The recitation, "a derivative" in claim 15 (part c) and claim 16 (part c) render claims indefinite. The recitation, "a derivative" is not clearly defined in the specification. Hence, one of ordinary skill in the art could not ascertain and interpret the metes and bounds of the patent protection desired as to "a derivative" of compounds herein, since one of ordinary skill in the art would clearly recognize that many various groups could possibly substituting these compounds. As a result, any significant structural variation to a compound would be reasonably expected to alter its properties, e.g., physical, chemical, physiological effects and functions. Thus, it is unclear as to what "a derivative" of compounds herein would be encompassed thereby.
Regarding claim 15 (parts a-c, d, e-i) and claim 16 (parts a-c and e-i) the phrase "not limited to" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Conclusion
Claims 1 and 11-16 are not allowed.
Claims 2-9 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHAR JAVANMARD whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1622
Prosecution Insights