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 92 and 93 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.
In evaluating the enablement question, several factors are to be considered. In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988); Ex parte Forman, 230 USPQ 546. The factors include: 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, and 7) the quantity of experimentation needed.
The nature of the invention in the instant case has claims, which embrace compounds 19, 24, 28, 54 and 206 substituted in the 17 positions with C(=O)-CH2-heteroaromatic rings.
HOW TO USE: The scope of claims 92 and 93 are not adequately enabled solely based on the modulation of the activity of a GABA receptor provided in the specification. Claims 92 and 93 are the method for treating a CNS-related disorder, which is not remotely enabled. The scope of claims 92 and 93 includes diseases and/or conditions not even known at this time, which may be associated with GABA receptor. While the treatment of schizophrenia has been linked with GABA receptor the art does not recognize use of such inhibitors as broad-based drugs for treating all disorders instantly embraced.
In addition, claims 92 and 93 embraces any and all central nervous system disorders. The scope of the method claims is not adequately enabled solely based on the inhibition of the GABA receptor provided in the specification.
The scope of "central nervous system disorder” cannot be deemed enabled. The term "central nervous system disorder” covers a broad array of different disorders that have different modes of action and different origins. The neurodegenerative disease covers such diverse disorders as Alzheimer's Disease; Parkinson's Disease; ALS and variants such as forms of ALS-PDC; Gerstmann-Straussler-Scheinker Disease (GSS); Pick's Disease; Diffuse Lewy Body Disease; Hallervordon-Spatz disease; progressive familiar myoclonic epilepsy; Corticodentatonigral degeneration; progressive supranuclear palsy (Steele-Richardson-Olszewski); Huntington's disease; more than a dozen dementias collectively called "frontotemporal dementia and Parkinsonism linked to chromosome 17" (FTDP-17); Tourette's syndrome; Shy-Drager syndrome; Friedrich's ataxia and other spinocerebellar degenerations; Olivopontocerebellar atrophy (OPCA); spasmotic torticollis; Striatonigral degeneration; various types of torsion dystonia; certain spinal muscular atrophies, such as Werdnig-Hoffmann and Wohlfart-Kugelberg-Welander; Hereditary spastic paraplegia, Primary lateral sclerosis; peroneal muscular atrophy (Charcot-Marie-Tooth); Creutzfeldt-Jakob Disease (CJD); Hypertrophic interstitial polyneuropathy (Dejerine-Sottas); retinitis pigmentosa; Leber's Disease; and Hypertrophic interstitial polyneuropathy. These exhibit a very broad range of effects and origins. For example, some give progressive dementia without other prominent neurological signs, such as Alzheimer's disease, whereas other dementias have such signs, such as Diffuse Lewy Body Disease. Some give muscular wasting without sensory changes, e.g. ALS, and some do have the sensory changes such as Werdnig-Hoffmann. Some are abnormalities of posture, movement or speech, such as Striatonigral degeneration, and other are progressive ataxias, such as OPCA. Some are linked to tau mutations, such as Alzheimer's disease and FTDP-17, and other such as Parkinson's clearly do not. Some affect only vision such as retinitis pigmentosa. Even within those that fall into the same category of effects, there are often striking differences. For example, Alzheimer's disease and Pick's disease both give progressive dementia without other prominent neurological signs. But the characteristic Alzheimer's neurofibrillary tangles are not seen in Pick's Disease, which has straight fibrils, as opposed to the paired helical filaments of Alzheimer's disease. Pick's Disease gives lobal atrophy, not seen in Alzheimer's disease. There are differences in origins, even with what little is known. Thus, among progressive dementias, CJD is definitely caused by an infectious agent; so far as can be determined, this is not so for Huntington's disease. Even among the hereditary disorders, the origins are different. Thus, FTDP-17 comes from chromosome 17, Huntington's disease from 4, and the neurodegenerative disorder that people with Down's syndrome develop later in life is presumably connected in some way to 21.
The great majority of these have no treatment at all, and of those that do, none or virtually none have been treated with such inhibitors as are disclosed here. The great diversity of diseases falling within the neurodegenerative disorders category means that it is contrary to medical understanding that any agent (let alone a genus of trillions of compounds) could be generally effective against such diseases. The intractability of these disorders is clear evidence that the skill level in this art is low relative to the difficulty of the task. Further, what little success there has been does not point in this direction. Thus, what very few treatments that the massive research effort on Alzheimer's disease has produced are means of providing Acetylcholinesterase inhibition, unrelated to the mechanism of action in this case.
No screening protocol(s) are ever described. Thus, no evidence of in vitro effectiveness is seen in the specification for one of the instantly claimed substituted imidazo[5,1-d][1,2,3]triazolo[1,5-a][1,5]benzodiazepine compounds. In general, pharmacological activity is a very unpredictable area. In cases involving physiological activity "the scope of the enablement obviously varies inversely with the degree of unpredictability of the factors involved." In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970). Since this case involves unpredictable in-vivo physiological activities, the scope of the enablement given in the disclosure presented here was found to be low.
The scope of "withdrawal symptoms caused by termination of use of addictive substances" cannot be deemed enabled. The notion that a compound could be effective against chemical dependencies in general is contrary to our current understanding of how chemical dependencies operate. There is not, and probably never will be, a pharmacological treatment for "drug addiction" generally. That is because "drug addiction" is not a single disease or cluster of related disorders, but in fact, a collection with relatively little in common. Addiction to barbiturates, alcohol, cocaine, opiates, amphetamines, benzodiazepines, nicotine, etc all involve different parts of the CNS system; different receptors in the body. For example, cocaine binds at the dopamine re-uptake site. Heroin addiction, for example, arises from binding at the opiate receptors, cigarette addiction from some interaction at the nicotinic acid receptors, many tranquilizers involve the benzodiazepine receptor, alcohol involves yet another system, etc. All attempts to find a pharmaceutical to treat chemical addictions generally have thus failed.
Where the utility is unusual or difficult to treat or speculative, the examiner has authority to require evidence that tests relied upon are reasonably predictive of in vivo efficacy by those skilled in the art. See In re Ruskin, 148 USPQ 221; Ex parte Jovanovics, 211 USPQ 907; MPEP 2164.05(a).
Patent Protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. Tossing out the mere germ of an idea does not constitute enabling disclosure. Genentech Inc. v. Novo Nordisk 42 USPQ2d 1001.
Claim Objections
Claims 94-105 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Allowable Subject Matter
Claims 74-91 are allowed. None of the prior art of record nor a search in the pertinent art area teaches the compounds, compositions and method of use of the 5 species claimed herein.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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