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 .
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 1-19 and 21 are rejected under 35 U.S.C. 112, 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.
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 nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
Nature of the invention and Breadth of the claims:
Claims are directed to a method of preventing Raybaud’s. The subject population of claim 1is not limited and encompasses any subject. The dose required to achieve claimed prevention is also not limited and includes any dose of compound 1. Compound 1 is known as APD791 and will be referred to as such.
State of the prior art and level of predictability in the art:
On page 1 of the specification applicants disclose:: “Raynaud’s presents in primary and secondary forms. The cause of primary Raynaud’s is not known. Vascular abnormality with this form is thought to be purely functional and reversable without progressing to irreversible tissue injury. However, some cases of primary Raynaud’s progress to secondary. The specification also discloses “Raynaud’s is complex and likely involves an interplay between vascular factors, neural control mechanisms, and intravascular factors. Treatment approach for Raynaud’s is consistent in mild cases, but diverges in cases involving moderate to severe digital ulceration or underlying systemic sclerosis”.
APD791 is selective 5-HT2A receptor antagonist. With regards to use of selective 5-HT2A receptor antagonists in treatment or prevention of Raynaud’s, Nagamoto et al (Pharmacology and Therapeutics, 2004, 104, 59-81) discloses administration of sarpogrelate, a selective 5HT2A receptor antagonist, to subjects with systemic sclerosis to study its effect on Raynaud’s phenomenon. Nagamoto teaches a significant decrease was found in frequency and duration of Raynaud’s phenomenon as well as symptoms associated with it (page 74, column 2, first paragraph). Nagamoto demonstrates that administration of an agent with the same activity as APD791 has failed to prevent the occurrence of Raynaud’s phenomenon.
Amount of direction provided by the inventor and existence of working examples:
Working examples merely show the half life of medication and its effect on recovery time. Example 5 only indicates future studies and that the compound has efficacy on subjects with Raynaud’s or that the compound can prevent the occurrence of Raynaud’s.
Although, the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), lack of a working example is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
Relative skill of those in the art and quantity of experimentation needed to make or use the invention:
Although the relative level of skill in the art is high, one of ordinary skill would not be able to treat cancer according to the claimed method without engaging in undue experimentation. Art suggests that 5HT2A receptor antagonism does not prevent occurrence of Raynaud’s and applicants have not provided any data that would suggest the opposite. Art demonstrates that Raynaud’s can be treated in subjects with systemic sclerosis via 5HT2A receptor antagonism, however the claimed subject population is not limited to those with systemic sclerosis and no data has been provided suggesting that 5HT2A antagonism can treat Raynaud’s in a population that does not have systemic sclerosis.
Thus, given these considerations, one of ordinary skill in the art clearly would not be able to practice the claimed method such that it can be used as contemplated in the specification without first engaging in substantial and undue experimentation. Therefore, the claims are rejected under 35 U.S.C. §112, first paragraph, as lacking and enabling disclosure.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-19 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagamoto et al (Pharmacology and Therapeutics, 2004, 104, 59-81) in view of Adams et al. (Journal of Pharmacology and Experimental Therapeutics, 2009, 331(1), 96-103; submitted by application on 6/9/25).
Scope of prior art
Nagamoto teaches antagonists of 5-HT2A receptor and their therapeutic applications. Nagamoto teaches administration of sarpogrelate, a selective 5HT2A receptor antagonist, to subjects with systemic sclerosis to study its effect on Raynaud’s phenomenon. Nagamoto teaches a significant decrease was found in frequency and duration of Raynaud’s phenomenon as well as symptoms associated with it (page 74, column 2, first paragraph).
Ascertaining the difference
Current claims differ from Nagamoto in that a different selective 5-HT2A receptor antagonist is administered. While Nagamoto teaches sarpogrelate, current claims are directed to compound 1, which is also known as APD791.
Secondary reference
Adams teaches APD791 and it’s activity as a 5-HT2A receptor antagonist. Adams teaches that APD791 is a 5-HT2A receptor antagonist like ketanserin, sarpogrelate, and AR246686 but with improved selectivity and pharmacokinetic profile (page 102, column 2, last paragraph; page 103, last paragraph).
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to try treating Raynaud’s phenomenon in subject with systemic sclerosis by administering to said subject APD791. From Nagamoto it is known that selective 5-HT2A receptor antagonist sarpogrelate can be used for treatment Raynaud’s phenomenon in subject with systemic sclerosis. It would have been obvious to substitute APD791 for sarpogrelate because Adams teaches APD791 be a selective 5-HT2A receptor antagonist that is an improvement over the previous agents including sarpogrelate. There is reasonable expectation of success because APD791 has the same physiological activity as sarpogrelate. There is motivation to try because Adams teaches APD791 to be an improvement.
Regarding claims 2-9, 16-18:
Claims 2-9 are directed to either symptoms or causes of Raynaud’s disease. Since Nagamoto teaches improvement in symptoms in Raynaud’s disease caused by systemic sclerosis, it would have been obvious to treat any subject who has Raynaud’s disease with an expectation that an improvement in symptoms would be achieved.
Claims 16-18 are directed to reduction in symptoms. Reduction in frequency and severity of symptoms is expected in view of Nagamoto.
Regarding Claims 10-15:
Claims 10-15 are directed to route of administration and form of the composition.
Both Nagamoto and Adams teach oral administration (Adams teaches this in the last paragraph).
A skilled artisan would have found it obvious to formulate APD791 into a suitable oral form which encompasses tablets and capsules. A skilled artisan would have also found it obvious to prepare APD791 as a pharmaceutically acceptable HCl. It is well known in the art to prepare HCl salts of active agents with the goal of improving dissolution and for preparation of stable formulations.
Lastly, a skilled artisan would have found it obvious to determine through routine experimentation the optimal effective and safe dose of APD791 for treatment of Raynaud’s disease.
Conclusion
Claim(s) 1-19 and 21 are pending
Claim(s) 1-19 and 21 are rejected
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628