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 .
DETAILED ACTION
STATUS OF THE CLAIMS: Claims 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 are pending in this application.
Claim Objections
Claims 94 and 99 are objected to because of the following informalities: claims 94 and 99 recite “PCNA”. Examiner suggest adding the full name followed by in parenthesis “PCNA”. Appropriate correction is required.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 (including claims dependent thereon and claims that relate back to independent claim 1) 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 pre-AIA the applicant regards as the invention.
(a) Claims 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 as heteroaryl, heterocyclyl, and/or aryl (e.g., ring A). The terms are indefinite since the specification does not define the ring size, heteroatom, number and nature of substituents, and the exact point of contact with the atom(s) for the substituents.
(b) Claim 99 is indefinite and rejected because it lacks a host (e.g., cell). As drafted, the claim fails to particularly point out the recipient of the asserted therapy or treatment option, and does not distinctly claim the mode or manner of administration to a host in need of said therapy or treatment. Correction is required.
Claim Rejections - 35 USC § 112, 1st 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.
Claim 94 is directed to a method of treating diseases associated with PCNA activity. In light of this, it can be asserted that 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 diseases associate with PCNA activity. In re Hokum, 226 USPQ 353 (ComrPats 1985).
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
The breadth of the instant claims is seen to encompass methods for treating diseases associated with PCNA activity, by administering to a patient in need of such treatment a therapeutically effective amount of the compound of formula I. Applicant failed to exactly define what types of conditions are treated. Thus, the claims are extremely broad.
The nature of the invention
The nature of the invention is the treatment of these disorders through the use of the claimed compound and derivatives thereof of formula I. Currently, there are no known agents that treat these diseases all inclusively.
The level of predictability in the art
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.
The applicant has not demonstrated sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to the same in the prior art to provide a skilled artisan with sufficient guidance to practice the instant treatment of disorders claimed. Further, the applicant discloses that an effective amount of the compound will be administered without providing any direction other than that the compounds of the invention have a high therapeutic index and follows this with a definition readily found in a basic pharmacology textbook. It should be noted that the therapeutic index of a drug in humans is almost never known and is only determined through clinical experience.
The existence of working examples.
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating these disorders. 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. 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 the disorders with the claimed compound.
The level of one of ordinary skill.
The level of skill is that of one with a doctoral understanding of diseases associate with PCNA activity’ therapeutics. Applicant’s data is not convincing as to make the production and use of pharmaceutical compositions comprising the recited compounds feasible without undue, un-predictable experimentation.
The quantity of experimentation.
A great deal of experimentation is required for the method of treating these disorders. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of different types of diseases with the claimed compound individually or in combination with other therapeutic agents.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for the treatment of diseases associated with PCNA activity.
Claim 95 is 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 claim(s) contains 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.
Claim 95 is directed to a method of treating cancer. The term cancer is interpreted to include any and all forms of cancer. In light of this, it can be asserted that 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 because it 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. In re Hozumi, 226 USPQ 353 (ComrPats 1985).
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
The breadth of the instant claims is seen to encompass methods for treating cancer by administering to a patient in need of such treatment a therapeutically effective amount of compound of formula (I). Thus, the claims are extremely broad.
The nature of the invention
The nature of the invention is the treatment of cancer through the use of the claimed compound and derivatives thereof. Currently, there are no known agents that treat cancers all inclusively. (See Pinedo et al. pages 1-2).
The level of predictability in the art
The treatment of cancer is highly unpredictable due to the differing forms of cancerous cells, their location, their potential for metastases, the fact that cancer therapeutics is palliative rather than curative and that cancer treatment readily harms normal tissues. (See McMahon, page 5, col. 2).
The amount of direction provided by the inventor.
The applicant has not demonstrated sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to the same in the prior art to provide a skilled artisan with sufficient guidance to practice the instant treatment of cancer claimed. Further, the applicant discloses that an effective amount of the compound will be administered without providing any direction other than that the compounds of the invention have a high therapeutic index and follows this with a definition readily found in a basic pharmacology textbook. It should be noted that the therapeutic index of a drug in humans is almost never known and is only determined through clinical experience.
The existence of working examples.
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating cancer. 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 of cancer. 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 cancer with the claimed compound.
The level of one of ordinary skill.
The level of skill is that of one with a doctoral understanding of cancer therapeutics.
The quantity of experimentation.
A great deal of experimentation is required. In order for there to be a method of treating cancer generally, as claimed by the applicant, it would be necessary to show that a vast range of different types of cancers can be treated that have differing cell types, locations and potentials for metastases. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of different types of cancer with the claimed compound individually or in combination with other therapeutic agents.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for the treatment of cancer.
Claims 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 are (including claims dependent thereon and claims that relate back to or refer to independent claim 1) are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for some of the A ring and B ring listed within the specification of the current application, does not reasonably provide enablement for all of the A and B rings listed within the application. 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 the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPX 546 (BD. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
1. Amount of guidance provided by Applicant.
While the Applicant has demonstrated within the application a select number of the aryl rings, heterocyclic rings and bicyclo-heterocyclic rings, the generic claims according to formula I are massive, and only a small fraction of these compounds are disclosed, discussed, and/or their synthesis shown. In the claims and specification, applicants claim various variables for ring A and ring B, which includes for rings A and B as well as various “R” groups that are aryl, heteroaryl, and heterocycyl and etc. groups. However, the specification fails to teach all of these compounds, nor does the specification define the ring size, heteroatom, number and nature of substituents, and the exact point of contact with the atom(s) for the substituents.
2. Unpredictability in the art.
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. (USPQ 18, 24 (CCPA 1970). See In re Fisher, 427 F.2d 833, 839, 166.
3. Number of working examples.
Applicants have provided working examples of the compounds (i.e., where rings A and B are defined); however, these examples only read on a minute portion of the massive claims according to general formula I in the present application.
4. Scope of the claims.
The scope, of the claims, involves a plethora of compounds of general formula I:
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152
380
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wherein all the variables are defined in the claim. For example, in defining ring A, ring B and some R groups:
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630
806
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Thus, the scope of the claims is very broad.
5. Nature of the invention.
The nature of this invention relates generally to some heterocyclic compounds for inhibiting PCNA activity, which plays a role in treating diseases associated with PCNA activity such as cancer.
6. Level of skill in the art.
The artisan using Applicant’s invention would be a chemist with a Ph.D. degree, and having several years of bench experiences.
MPEP § 2164.01 (1) 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).” Thus, this conclusion is clearly justified here. Therefore, Applicant is not enabled for all of these compounds or compositions.
Conclusion
Claims 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 are pending. Claims 1-2, 6, 10, 13, 20, 23, 25, 32, 36, 44, 50, 59, 87-88, 94-95, 99, 102 and 134 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL V WARD whose telephone number is (571)272-2909. The examiner can normally be reached M-F 9am to 5pm.
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/PAUL V WARD/ Primary Examiner, Art Unit 1622
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