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
Claims 20-38 are currently pending.
Claim Objections
Claims 21-36 and 38 are objected to because of the following informalities:
“A method” should instead read “The method” to properly denote dependency.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 20-38 are 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 the treatment or prevention of hallucinations or psychosis in a patient with Lewy body dementia comprising administering 75mg of mevidalen per day, does not reasonably provide enablement for the treatment or prevention of hallucinations or psychosis comprising administering a D1 positive allosteric modulator. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention (1) and breadth of the claims (6)
The nature of the invention and breadth of Claims 20-38 is the prevention or treatment of psychosis or hallucinations through administering a D1 PAM and additional agents, the D1 PAM including 5-60mg doses of mevidalen.
The state of the prior art (2) and the predictability or lack thereof in the art (3)
Biglan (WO2020131671, published 2020), sharing common inventors with the instant application, teaches that mevidalen, the claimed D1 PAM embodiment, induces treatment-emergent adverse events including hallucinations (Page 39, Study HBEC Part A). The effect of hallucination induction is the opposite of what is claimed, the prevention and treatment thereof. One would not predict that mevidalen would have the opposite effect of what is demonstrated in Biglan.
More generally, Vales (International Journal of Neuropsychopharmacology, Volume 12, Issue 7, August 2009, Pages 873–883) teaches D1R antagonism rather than agonism decreased hyperlocomotion and suggests increased activity may instead exacerbate psychotic symptoms in schizophrenic patients (Abstract). Psychosis and hallucinations are such symptoms.
Rolland (BioMed Research International Volume 2014, Issue 1. Article ID 307106, 9 pages) suggests instead that D1R are implicated in negative symptoms rather than positive symptoms like psychosis (Page 2, 2.1 The Dopamine Model, Para 1). Therefore, one of skill in the art might expect to treat negative symptoms by practicing the claimed method step in a patient in need thereof. However, Rolland teaches away from using the claimed PAM to treat positive symptoms.
In view of the prior art, one of ordinary skill in the art might expect the administration of mevidalen to induce hallucinations or be totally ineffective in preventing psychosis.
The amount of direction or guidance present (4) and the presence or absence of working examples (5)
Applicant tests three distinct dose amounts of mevidalen for the treatment of hallucinations in patients with Lewy Body Dementia (Spec: Fig. 1). The 10 and 35 mg doses did not yield significant results (p>0.05) whereas the only dose to yield significant reduction of hallucinations in the PRESENCE study was 75mg (p<0.01). Applicant does not claim the only successful dose amount in the cited methods, nor does applicant explain why the same results would be expected from lower dose amounts. Further, applicant fails to explicate why the method of administering one successful dose of mevidalen in the select patient population is extrapolated to any patient group, any D1 PAM, in any amount.
The quantity of experimentation needed (7)
The quantity of experimentation needed is extremely difficult, novel, and undue experimentation; the ability of the method to yield successful results is nearly impossible to determine and not at all enabled by the experiments disclosed in the specification of the application. The art is clear regarding the inefficacy of D1R agonism in the treatment of symptoms like psychosis and hallucinations. The inventor’s own work, before the filing of this application, also supports that mevidalen is not expected to be effective to reduce hallucinations. The single successful trial group is insufficient to overcome what is known in the art with respect to applicant’s scope and would thus require a great degree of undue experimentation to identify potentially successful dose amounts, D1R modulator species, and patient populations.
The level of the skill in the art (8)
The level of skill in the art is high; however, the state of the art at the time of filing contradicts applicant’s suggestion that the claimed symptoms can be treated as claimed in the broad methods. One of even the highest skill in the pharmaceutical arts, especially in view of the induction of hallucinations reported by the inventors in a separate work, would not expect to successfully practice the scope of the invention as claimed.
Closest Prior Art
The closest prior art to the claimed methods is found in Beadle (WO2014193781). Beadle teaches mevidalen for the treatment of schizophrenia (Claims 6, 7, and 16). However, Beadle teaches that the treatment is limited to negative symptoms, not positive symptoms as claimed (Page 1, Lines 22-27).
Conclusion
No claim is allowable.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627