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 1-29 are pending in this application.
Examiner Notes/Foreign Priority
Examiner notes the following:
Applicants have made a claim for foreign priority; however, certified copies of the priority documents have not been received;
International documents (e.g., PCT search reports and etc.) have not been filed with this application; and
An IDS has not been filed with this application.
Information Disclosure Statement
Examiner notes that an IDS has not been filed with this application. Examiner suggests filing an IDS.
Specification
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
Claim Rejections - 35 USC § 112, 2nd paragraph
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 1-29 (including claims dependent thereon are claims that relate back to independent or dependent claims) rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
(a) Claims 1-29 recite heteroaryl, heterocyclic, heteroarylene, heteroaromatic and/or aryl, etc., and aromatic. 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. Correction is required.
(b) Regarding claim 23, the phrases "as shown in Table 1 or Table 2” render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Applicant is reminded that a claim should be complete by itself. These claims are deemed to be incomplete because it incorporates reference to compounds or a table in the specification. Examiner suggests adding the compound to the claim (structure or name). Correction is required.
(c ) Regarding claim 26, the phrase "or other disease or disorder" at the end of the claim renders the claim indefinite because it is unclear what diseases or disorders are part of the claimed invention. See MPEP § 2173.05(d).
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 1-29 (including claims dependent thereon are claims that relate back to independent or dependent claims) 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 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.
Claims 1, 4, 8 and 23-25 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for specific compounds disclosed in the specification, does not reasonably provide enablement for prodrugs and solvates of those compounds and composition containing same. 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.
The claims are rejected because the claims recite specific compounds and prodrugs and solvates of said compounds. However, the specification fails to teach the preparation or identity of prodrugs and solvates. Therefore, the specification is not adequately enabled for making and/or using prodrugs and solvates.
Identifying an ester requires knowledge of in vivo regeneration pathways of instant compounds and short of extensive experimentation, would be the skilled artisan would need much more data to determine prodrugs and solvates of the instant compounds and compositions.
Applicants have not provided any clear guidance that would provide prodrugs and solvates of the instant compounds that will regenerate in vivo to the instant compounds by one or more biological processes or methods for preparing prodrug and solvates and solvates s. It is not the norm that one can predict with any accuracy whether a particular ester form of an active compound will be more soluble, more easily handled in formulations or more bioavailable without art recognized data to support same. The specification provides no guidance as to what type(s) of prodrugs and solvates are suitable for the instant compounds. Generally, prodrugs and solvates themselves are not considered to be therapeutically active but only to provide the active compound in vivo.
For rejections under 35 U.S.C. 112, first paragraph, the following factors must be considered (In re Wands, 8 USPQ2d 1400, 1404 (CAFC, 1988)):
1) Nature of invention.
2) State of prior art.
3) Quantity of experimentation needed
4) Level of predictability in the art.
5) Amount of direction and guidance provided by the inventor.
6) Existence of working examples.
7) Breadth of claims.
8) Level of ordinary skill in the art.
Nature of the invention
The nature of the invention is the preparation of compounds and compositions under the genus of a structural formula. As stated, however, prodrugs and solvates are also intended. The nature of prodrugs and solvates is not set forth nor is the manner in which the prodrugs and solvates are to be prepared or the core compounds modified prodrugs and solvates.
State of the prior art
The state of the prior art is that acceptable salts are known in the pharmaceutical industry. Prodrugs and solvates in related compounds are not modified.
Quantity of experimentation needed
The quantity of experimentation needed is undue. The skilled artisan would need to regenerate in vivo the instant compounds by one or more biological processes. All of which require undue experimentation. Applicant has not postulated a metabolic pathway or mechanism, which facilitate conversion of the prodrugs and solvates into an active agent.
Level of predictability in the art
The art pertaining to the preparation and use of esters is high as prodrugs and solvates are compound specific and not all prodrugs and solvates have the ability to regenerate in vivo. (See “Wolff, M.E., “Burger’s Medicinal Chemistry”, pp. 975-977, and Banker et al., “Modern Pharmaceuticals”, p. 596).
Amount of direction and guidance provided by the inventor
There is no guidance provided as all the examples in the specification are drawn to the preparation of compounds disclosed in the specification and not prodrugs and solvates. The lack of guidance to prepare any esters is not provided by the inventor.
Existence of working examples
As discussed above, working examples are drawn to the preparation of compounds disclosed in the specification and not to prodrugs and solvates. The lack of guidance to prepare any prodrugs and solvates is telling. There is no direction or guidance provided by Applicant to prepare prodrugs and solvates of the instant invention.
Breadth of claims
The breath of the recited compounds and compositions in the claims includes prodrugs and solvates for which there have been provided no specific examples or procedural steps to prepare prodrugs and solvates. Failure to teach how to make the instant compounds makes teaching how to use the compounds unduly difficult, if not impossible.
Level of ordinary skill in the art
The level of ordinary skill in the art is high due to the unpredictability in the chemical art.
Hence, as discussed above, to practice the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation to test which prodrugs and solvates can be used in the instant claim, with no assurance of success. Therefore, applicant must show that the specification teaches the preparation of prodrugs and solvates, or limit the claims accordingly.
Claims 1-29 are (including claims dependent thereon and claims that relate back to or refer to independent or dependent claims) are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for some of the ring B, L1, L2 and various R groups listed within the specification of the current application, does not reasonably provide enablement for all of the ring B, L1, L2 and various R groups 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 heterocyclic compounds, the generic claims according to formula I (i.e ring B, L1, L2 and various R groups—e.g., aryl, heteroaryl, aromatic, heterocyclic) are massive, and only a small fraction of these compounds are disclosed, discussed, and their synthesis shown. In the claims and specification, applicants claim the following compound according to formula I:
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154
186
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,
wherein the various variables for heterocyclic core, includes for ring B, L1, L2 and R groups and as well as various “R” and L1, L2 groups that are aryl, heteroaryl, heterocyclic, heterocyclyl, heteroarylene, arylene, heteroalkene 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/or 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 some working examples of the compounds (i.e., where ring B is a 5-membered or 6-membered heteroaryl, L1, L2 and various R groups 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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154
186
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wherein all the variables are defined in the claim. For example, in defining ring B as an optionally substituted 5-membered or 6-membered, and the following:
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250
812
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506
826
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472
818
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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 modulating calcitonin receptor and/or amylin receptor activity, which plays a role in treating calcitonin receptor and/or amylin receptor diseases and disorders.
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.
Claims 25-26 (including claims dependent thereon) 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 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.
Claims 25-26 are directed to a method of treating calcitonin receptor and/or amylin receptor diseases and disorders.
In light of this, it can be asserted that in spite of the vast expenditure of human and capital resources in recent years, there are no agents that treat all calcitonin receptor and/or amylin receptor diseases and disorders. 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 claim 25 is seen to encompass a method for treating calcitonin receptor and/or amylin receptor disorders by administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula I, which includes bone disorders, metabolic disorders, pain, neurodegenerative disorders, cardiovascular diseases or “other diseases or disorders”. Applicant fail to specify a particular disorder. Thus, the claim is extremely broad.
The nature of the invention
The nature of the invention is the treatment of calcitonin receptor and/or amylin receptor disorders through the use of the compounds of formula I thereof. Currently, there are no agents 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 of these disorders with all of the compounds of formula I. 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 these disorder 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 calcitonin receptor and/or amylin receptor diseases and disorders.
Conclusion
Claims 1-29 are pending. Claims 1-29 are rejected. No claims are allowed.
Examiner Notes/Foreign Priority
Again, Examiner notes the following:
Applicants have made a claim for foreign priority; however, certified copies of the priority documents have not been received;
International documents (e.g., PCT search report and etc.) have not been filed with this application; and
An IDS has not been filed with this application.
Examiner suggests filing the documents enumerated above.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL V WARD/ Primary Examiner, Art Unit 1622
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