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, 3, 6-7, and 9-10 are pending in the instant application.
Claims 2, 4-5, and 8 have been canceled.
Withdrawn Objections/Rejections
Applicant’s amendment is sufficient to overcome the rejection of Claims 1-5 and 7 under 35 U.S.C. 112(a). The cancellation of Claims 2 and 4-5 renders the rejection thereof moot. This rejection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claims 8-10 under 35 U.S.C. 101. The cancellation of Claim 8 renders the rejection thereof moot. This rejection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claims 1, 5, and 7 under 35 U.S.C. 102(a)(2). The cancellation of Claim 5 renders the rejection thereof moot. This rejection is hereby withdrawn.
Election/Restrictions
Newly amended claims 9-10 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claims 1, 3, and 6-7 are drawn to a product. Claims 9-10, as amended, are drawn to methods of using that product. The product of Claims 1, 3, and 6-7 can be used for materially different purposes than the method as claimed in Claims 9-10, for example, for in vitro experiments not directed toward treating a patient. Similarly, Claims 9-10 can be practiced with compounds materially different than those of Claims 1, 3, and 6-7. For example, Claims 9-10 can be practiced with materially different SHP-2 inhibitors.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 9-10 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
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, 3, and 6-7 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of formula I’ or a pharmaceutically acceptable salt, stereoisomer, or solvate thereof, does not reasonably provide enablement for a prodrug of a compound of formula I’. 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 these claims.
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 compounds or pharmaceutically acceptable salts, stereoisomers, solvates, or prodrugs thereof of the formula I’:
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Breadth of the invention:
The scope of the claimed invention is very broad. In addition to being drawn to any compound of the above formula, allowing for myriad combinations of the variables as defined, for example at instant Claim 1. With respect to prodrug, the term is broadly defined at Page 15 of the instant specification, as any compound that “undergoes metabolism or chemical reactions in human body to convert into a class of compounds of formula I’, or a salt or solution of compound of formula I’.” This includes a wide array of structurally distinct moieties readily envisaged by a person having ordinary skill in the art.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
With respect to the use of prodrugs, Walther et. al. (“Prodrugs in medicinal chemistry and enzyme prodrug therapies”, Adv. Drug Deliv. Rev., 2017, 65-77) represents the state of the prior art.
At Page 66, Table 1, Walther teaches that prodrugs are typically employed when,f or example the parent drug compound has poor aqueous solubility, poor absorption from the gastro-intestinal tract into the blood, poor rates of cell entry, or various other reasons. Further, design strategy for a prodrug depends on the structural features of the parent drug molecule and availability of the appropriate chemical functionalities that can be used to mask pharmacodynamic activity of the drug through an attachment of a modifying group. Typically, an enzymatic process is relied upon for drug release.
To this end, compounds of formula I’ contain a plethora of moieties that a person having ordinary skill in the art would readily recognize as susceptible to modifications to generate prodrug compounds. No guidance has been provided in the instant application, however, that would instruct a person having ordinary skill in the art which prodrugs are suitable for use with the instant invention, nor would it be readily understood based on the content of the instant disclosure the motivation for generating a prodrug moiety.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any prodrug of a compound of formula I’.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples of the description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.1(p).
MPEP § 2164.01(a) states, “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, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). That conclusion is clearly justified here that Applicant is not enabled for making the broadly claimed prodrugs of compounds of formula I’.
Conclusion
Claims 1, 3, and 6-7 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
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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