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 Status
Pending claims 20-37 have been examined on the merits.
Claim Rejections - 35 USC § 112 (Enablement)
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 20-37 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 20 recites “a method of slowing progression of Parkinson's Disease,” by administering a dopamine D 1 positive allosteric modulator (D1 PAM), such as mevidalen to a patient population categorizes a prodromal, Early-stage, Advanced stage Parkinson's
Disease, and for Parkinson's disease. The specification (page 24) discloses a 12-weeks phase 2 PRESENCE study (NCT03305809) in patients with Lewy Body Dementia (LBD) showing statistically significant symptomatic improvement in global functioning (ADCS-CGIC). Such outcomes are indicative of symptomatic improvement or stabilization, but given that Parkinson’s disease progression is generally understood in the art as the rate of long-term disease worsening due to ongoing neurodegeneration, typically assessed over extended periods by drastic changes in disease severity, disability milestone, or even rate of decline analyses, as an example. The specification clearly fails to demonstrate data demonstrating a reduced rate of disease progression, delayed progression milestone, as evidence of the intervention significantly slowing the disease expected outcome. Although the specification (page 23) defines “slow progression” as
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However, redefining the term does not automatically establish possession of a method that actually slow disease progression as a POSITA would understand it in the art. This is because, a POSITA would distinguish between short-term symptomatic benefit and true “slowing of Parkinson’s disease progression,” and clearly the specification fails to separate the two distinct outcomes. This is supported by the specification with prophetic term of expectation rather than absolute outcome (page 4 bridged page 5)
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These statements are solely expressed in speculative or hypothetical terms and are not supported by experimental evidence, demonstrating reduced neurodegenerative or decreased rate of disease worsening. Furthermore, specification appears to use mild-to-moderate Lewy Body Dementia (Parkinson's disease dementia - PDD or Dementia with Lewy Bodies - DLB) as prodromal and Early-stage Parkinson's disease population, which is not clinically accurate. Furthermore, the specification does not provide examples of patient population to represent Advanced stage Parkinson's disease.
The specification’s failures to disclose a proper representative of the patient population and progression endpoints of the disease, thereof supports the conclusion that the specification lacks adequate written description or enablement of the claimed subject matter indicating that Applicant was not in possession of the entirety of the claimed genus at the time of filling of the instant application in view of the disclosure of the application as filed.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office
action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
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.
Claims 20-37 are rejected under 35 U.S.C. 103 as being unpatentable over Valde Anne, (WO2021/001286), in view of RN 1638669-32-5 (14 Dec 2014) and Abdel-Magid AF. ACS Med Chem Lett. 2015 Jan 8;6(2):104-7.
Regarding claim 20, Valade (page 1-2; page 5) teaches a method of treatment and/or prevention of Parkinson's disease with a dopamine D1 Positive Allosteric Modulator (D1 PAM) comprises administering to a patient in need of such treatment of an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof. While Valade does not explicitly teach “slowing progression,” however, a person of ordinary skill in the art (POSITA) would understand that treatment of progressive disease is reasonably expected to slow, delay, or mitigate disease progression, as opposed to merely providing transient symptomatic relief. As evidence by the specification (page 23)
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Regarding claims 21-24, Valade does not explicitly teach the use of D1 PAM for treating untreated patient, prodromal, Early-stage, and Advanced stage Parkinson’s disease. But it is well-understood in the art that Parkinson’s disease is a progressive disorder that presents along a continuous of stages. Therefore, a POSITA would also recognize that any patient with Parkinson’s disease necessarily falls within one of these stages. Furthermore, a POSITA would also recognize that designation of a treatment for a particular disease stage does not imply that the treatment would be infective or unsuitable for other stage of the same disease. For example,
it is well-known in the art that dopamine replacement therapy (e.g., levopoda) is used across all stages of Parkinson’s disease, including untreated patients population, to compensate for the progressive loss of dopanergic signaling. Given that D1 PAM is known to potentiate endogenous dopamine signaling via allosteric mechanism, enhancing dopamine receptor activity, which mirrors or overlaps with levodopa’s adaptability for dopamine signaling restoration, which would then lead to the use of D1 PAM across the Parkinson’s disease stages, because both strategies addressing a dopamine deficit to improve motor and cognitive function.
Regarding claim 25, Valade does not explicitly teach mevidalen.
However, as applied to claims 20-25 above, RN 1638669-32-5 teaches a compound Mevidalen hydroxybenzoate, a D1 PAM, but does not explicitly disclose its use to treat
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Parkinson’s disease. Nonetheless, Abdel-Magid teaches (104-105) discloses a structurally similar compound and teaches its use for the treatment of Parkinson’s disease. Therefore, it would have
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been obvious to a POSITA to modify Valade’s teachings in view of RN 1638669-32-5 and Abdel-Magid, by including mevidalen as part of therapeutic intervention against Parkinson’s disease, to arrive at the claim intervention.
Regarding claims 26-37, Valade (page 7, line 13-15; page 8, lin2 5-8) teaches a pharmaceutical composition that can be administered orally, as an example, with a daily dosage range from 0.05 to 3000 mg. Given the combined references teaches the use of D1 PAM, e.g., mevidalen, to treat Parkinson’s disease at a dose range from 0.05 to 3000 mg, to slow progression of the disease; a POSITA would have been motivated to apply a comparable composition within an overlap dose range, to arrive at the claim invention as 5 to 50 mg dose falls with the disclosed dose by the combined prior art.
Conclusion
Therefore, claims 20-37 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H 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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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622