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 .
Upon further consideration pending claims 1-11, 16 and claims 14 and 15 are examined together.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-11, 16 and 14 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-14 of copending Application No. 18267331 further in view of Nomura US20170079915. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims contain overlapping subject matter:
Product claims 1, 10, 11 and 14 of 18267331 overlap with the instant product claims 1-11 and method claims 8, 9, 12, 13 of 18267331 overlap with the instant method claims 14 and 15 as explained below:
The active ingredient product/compound in the conflicting claims is the same compound (recited) in the instant claims.
The issue here is that the compound administered in the instant case is in amorphous form while in the copending case claims is silent with respect to specific polymorphic form of the compound. Thus the relationship is ‘genus (18267331) species’ (instant) with respect to polymorphic form of the active ingredient and specific inactive ingredients.
According to Nomura a solid dispersion for achieving improved solubility and absorbability of a pharmaceutically active ingredient, can be made with an amorphous form of the pharmaceutically active ingredient, (along with the excipients for example as per instant claim 11).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Note: NOA is found in file-wrapper of 18267331
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing
Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32
(2010) 324–330.
Claims 1-11, 16 and 14 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 6, 10 and 11 of copending Application No. 17621851 further in view of Nomura US20170079915.
:Product claims 1, 10, 11 of 17621851 overlap with the instant product claims 1-11 and 16 of instant claims which is the used in the instant method claims 14 and 15. .
The instant claims are drawn to the same compound of the claims of 17621851. The pharmaceutical composition of claim 6 of 17621851, for example, is silent with respect to polymorphic form of the active ingredient in it.
The active component/product/compound in the conflicting claims is the same compound (pictured). Making amorphous forms of API is within the purview of one of skill in the art. According to Nomura a solid dispersion for achieving improved solubility and absorbability of a pharmaceutically active ingredient, can be made with an amorphous form of the pharmaceutically active ingredient, (along with the excipients for example as per instant claim 11).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Note: NOA is found in file-wrapper of 17621851
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing
Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32
(2010) 324–330.
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 14, 15 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.
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 relevant factual considerations.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All the factors have been considered with regard to the claims, with the most relevant factors discussed below:
The instant claims are very broad in terms of type of diseases being treated, which include many CNS disorders: schizophrenia, cognitive impairment related to neuroleptic therapy, Mild Cognitive impairment (MCI), impulsivity, Attention-Deficit Hyperactivity Disorder (ADHD), Parkinson’s disease and other movement disorders, dystonia, Parkinson’s dementia, Huntington’s disease, dementia with Lewy Body, Alzheimer’s disease drug addiction, sleep disorders, apathy, traumatic spinal cord injury, neuropathic pain.
No data has been provided to indicate the effects of the compositions on either cellular or animal models commonly used in research for the claimed diseases/disorders. Instead disclosure in WO2021001288 is provided, which allegedly teaches the composition may be useful in treating any and all the diseases noted above. As inferred the pictured compound acts as a D1 Positive Allosteric Modulator ()hereinafter PAM) and is accordingly of benefit as a pharmaceutical agent for the treatment of diseases in which D1 receptors play a role.
No working examples consisting of administering the compound in a method of treatment and/or prevention for the disorders listed in instant claims 14, 15 are provided in applicant’s disclosure.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using the invention would generally be a physician with an M.D. degree and several years of experience.
As evidenced by Hall J Med Chem, 2018, 62:128-140, several other D1 receptor binding compounds are in clinical trials for the treatment of Parkinson’s disease and cognitive impairment associated with schizophrenia. It is an area of interest for more research to be conducted into D1 binding compounds (pg. 137). Hall teaches work of several research groups to identify compounds that selectively activate D1 receptor signaling was tackled in two ways, direct agonism and positive allosteric modulation. Hall further teaches the work of Lilly and NIH highlights that more than one PAM site may exist. It is apparent that despite appearing as a drug-like aminergic GPCR, the ligandablity and tractability of the D1 receptor has proven surprisingly low demonstrated by the HTS campaigns for Pfizer (for agonists) and Lilly (for PAMs), which both returned single hits.
Furthermore, molecules affecting D1 as agonists and PAMs are unpredictable in testing. For example, one experiment indicated that rat models would be ineffective in showing activity for D1 PAMs in human neural cells, as evidenced by Hall (pg. 136, column 1). It is also difficult to selectively target D1, as evidenced by Girmaw Health Sci Rep, 2024, 7:e1984, due to various pharmacological and chemical challenges (pg. 3, column 1, section 2.2, paragraph 1). For example, most D1 agonists are equipotent agonists at the D5 receptor which might be involved in blood pressure regulation, as taught by Hall (pg. 128, column 2 to pg. 129, column 1). As D1 PAMs are still an emerging drug class, the level of predictability in the art is uncertain.
Although the area has thus moved forward significantly in recent years, several unanswered questions still remain, such as the following: Which strategy is better, orthosteric agonism or positive allosteric modulation? Are there more than two allosteric sites? Which, if any, of the allosteric sites offers the most therapeutic potential? It is hoped that the answers to these and other questions will be solved in the coming years.
Transitioning to the diseases claimed, the current state of the art for Parkinson’s disease research includes cross-species preclinical models, including cellular models and animal models, as evidenced by Ke Aging and Disease, 2021, 12:223-246; (pg. 225, column 1). For example, Ke summarizes a list of immortal cell lines important in Parkinson’s disease modeling in Table 1 and discusses common animal models in Parkinson’s research. However, Ke teaches cell models are unable to recapitulate in vivo pathogenesis and pathophysiology requiring the interaction of different cell types (pg. 237, column 1, paragraph 1) and currently existing animal models exhibit their own distinct characteristics and limitations (pg. 237, column 1, paragraph 2).
Similarly, as evidenced by Blanchard Nat Rev Neurol, 2022, 18:25-39, Alzheimer’s disease research starts with different culture systems of varying levels of complexity which each pose unique advantages and limitations (pg. 26, column 1 and Table 1). For example, induced pluripotent stem cells derived from patients with familial Alzheimer’s disease have been used as a cell model to study specific mutations associated with Alzheimer’s (pg. 26, column 2). However, Blanchard teaches existing in vitro models only capture parts of the systems affected in Alzheimer’s and given the interconnected nature of the human brain and the need to comprehensively understand and target Alzheimer’s, there is a need to recreate all the major cellular components of the human brain in one model (pg. 35, column 2 to pg. 36, column 1). Thus there is currently an inherent unpredictability to any in vitro or in vivo studies performed to further Parkinson’s or Alzheimer’s disease research.
Finally, the disorders listed all have mutually exclusive etiology and pathophysiology and are drawn to a different patient populations making it difficult for a person having skill in the art to conduct the necessary experimentation to move forward with treatment. For example, subjects with Parkinson’s disease are diagnosed and treated with different methodologies than subjects with ADHD.
In weighing the above stated factors, it is the examiner’s position that “undue” experimentation is required to use the recited compounds in the claimed methods. In view of the state of the art and the instant disclosure, it is not possible for one of ordinary skill in the art to use the methods falling within the metes and bounds of the claims without "undue" experimentation.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/ Primary Examiner, Art Unit 1625
Prosecution Insights