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 .
Claims 1-11, 16-19 and 24-31 are pending in this application.
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 16 and 26 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 preeclampsia and pulmonary fibrosis, does not reasonably provide enablement for autoimmune disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
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 substituted imidazole-1-ylmethylphenylthiophene compounds.
HOW TO USE: Claims 16 and 26 is to a method of treatment of an autoimmune disease or fibrotic disease which is responsive to the angiotensin II agonist activity. Any evidence presented must be commensurate in scope with the claims and must clearly demonstrate the effectiveness of the claimed compounds. However, the specification provides no definitive evidence to correlate any one disorder selected from those disclosed in the specification with the instantly disclosed imidazole-1-ylmethylphenylthiophene compounds.
The analysis is as follows:
(A) Breadth of claims.
(a) Scope of the compounds. The instant claims encompass millions of compounds with a imidazole-1-ylmethylphenylthiophene scaffold with a variety of substituents at various positions.
(b) Scope of the diseases covered. The instant claims are drawn to a method of treating any and all autoimmune diseases and fibrotic diseases. Autoimmune diseases includes Acquired hemophilia, Acromegaly, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-NMDA receptor encephalitis, Antiphospholipid syndrome, Aplastic anemia, Arteriosclerosis, Autoimmune Addison’s disease, Autoimmune angioedema, Autoimmune autonomic ganglionopathy, Autoimmune encephalitis / acute disseminated encephalomyelitis (ADEM), Autoimmune gastritis, Autoimmune hemolytic anemia, Autoimmune hepatitis, Autoimmune hyperlipidemia, Autoimmune hypophysitis / lymphocytic hypophysitis, Autoimmune inner ear disease, Autoimmune Interstitial Lung Disease, Autoimmune lymphoproliferative syndrome, Autoimmune myelofibrosis, Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune pancreatitis, Autoimmune polyglandular syndromes, Autoimmune progesterone dermatitis, Autoimmune retinopathy, Autoimmune sudden sensorineural hearing loss, Balo disease / concentric sclerosis, Behçet’s disease, Birdshot chorioretinopathy, Bullous pemphigoid, Castleman disease, Celiac disease, Chagas disease, Chronic autoimmune urticaria, Chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, Cogan’s syndrome, Cold agglutinin disease, CREST syndrome, Crohn’s disease, Cronkhite-Canada syndrome, Cryptogenic organizing pneumonia, Dermatitis herpetiformis, Dermatomyositis, Discoid lupus, Dressler’s syndrome, Eczema / atopic dermatitis, Endometriosis, Eosinophilic esophagitis / eosinophilic gastroenteritis, Eosinophilic fasciitis, Erythema nodosum, Essential mixed cryoglobulinemia, Evans syndrome, Fibromyalgia, Fibrosing alveolitis / idiopathic pulmonary fibrosis, Giant cell arteritis / temporal arteritis / Horton’s disease, Giant cell myocarditis, Glomerulonephritis, Goodpasture’s syndrome / anti-GBM / anti-TBM disease, Granulomatosis with polyangiitis / Wegener’s granulomatosis, Graves’ disease, Guillain-Barrè syndrome, Hashimoto’s thyroiditis / autoimmune thyroiditis, Henoch-Schonlein purpura, Hidradenitis suppurativa, Hurst’s disease / acute hemorrhagic leukoencephalitis, Hypogammaglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, Immune thrombocytopenia / autoimmune thrombocytopenia purpura, Immune-mediated necrotizing myopathy, Inclusion body myositis, Interstitial cystitis, Juvenile idiopathic arthritis / adult-onset Still’s disease, Juvenile myositis, Kawasaki disease, Lambert-Eaton myasthenic syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosis, Linear IgA disease, Lupus nephritis, Lyme disease, Ménière’s disease, Microscopic polyangiitis / ANCA-associated vasculitis, Mixed connective tissue disease, Mucous membrane pemphigoid / ocular cicatricial pemphigoid, Multiple sclerosis, Myalgic encephalomyelitis / chronic fatigue syndrome, Myasthenia gravis, Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD), Narcolepsy, Neuromyelitis optica / Devic’s disease, Optic Neuritis, Palindromic rheumatism, Palmoplantar pustulosis, Paraneoplastic cerebellar degeneration, Paraneoplastic pemphigus, Paroxysmal nocturnal hemoglobinuria, Parry-Romberg syndrome / hemifacial atrophy / progressive facial hemiatrophy, Parsonage-Turner syndrome, Pemphigoid gestationis / herpes gestationis, Pemphigus foliaceus, Pemphigus vulgaris, Pernicious anemia, Pityriasis Lichenoides et Varioliformis Acuta (PLEVA) / Mucha-Habermann disease, POEMS syndrome, Polyarteritis nodosa, Polymyalgia rheumatica, Polymyositis, Postural orthostatic tachycardia syndrome, Primary biliary cholangitis (PBC), Primary sclerosing cholangitis, Psoriasis, Psoriatic arthritis, Pure red cell aplasia, Pyoderma gangrenosum, Raynaud’s syndrome, Reactive arthritis, Relapsing polychondritis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma / systemic sclerosis, Sjögren disease (SjD), Small fiber sensory neuropathy, Sydenham’s chorea, Systemic lupus erythematosus, Takayasu arteritis, Testicular autoimmunity / autoimmune orchitis, Thyroid eye disease / Graves’ ophthalmopathy / thyroid-associated orbitopathy, Transverse myelitis, Type 1 diabetes / insulin-dependent diabetes, Ulcerative colitis, Undifferentiated connective tissue disease, or Vitiligo.
(B) The nature of the invention and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(C) Direction or Guidance:
That provided is very limited. The dosage range information, found on pages 33 and 34 of the Specification gives about 0.1 mg to about 1000 mg, which is very broad. Moreover, this is generic, the same for the many disorders covered by the specification. Thus, there is no specific direction or guidance regarding a regimen or dosage effective specifically for any and all autoimmune diseases.
(D) State of the Prior Art:
These compounds are substituted imidazole-1-ylmethylphenylthiophene of any kind have been used for inhibiting or treating any and all autoimmune disease.
(E) Working Examples:
The invention is drawn to a method of treating one or more autoimmune disease. There are no working examples or even animal models, in the Specification drawn to this utility to support the use of substituted imidazole-1-ylmethylphenylthiophene to treat any and all autoimmune diseases. No screening protocol(s) are ever described. Thus, no evidence of in vitro effectiveness is seen in the specification for one of the instant imidazole-1-ylmethylphenylthiophene 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.
(F) Skill of those in the art:
These diseases and disorders disclosed in the Specification on page 25 cannot be treated generally by any one drug. These are all different diseases and disorders, which occur at different locations and by different modes of action in the body.
(G) The quantity of experimentation needed:
Owing especially to factors A, C, E and F, the amount of experimentation is expected to be high.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
The specification does not have working examples on the use of the substituted imidazole-1-ylmethylphenylthiophenes, etc. The absence of working examples is one of the factors to be considered in deciding whether the practice of an invention would involve undue experimentation. There must be evidence to justify the contention that the claimed compounds can be useful in the treatment of “autoimmune disease, etc.”.
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, 21 1 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 USPQZd 1001.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10, 16-19, 24 and 26-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The following reasons apply:
Claims 1, 7, 9 and claims dependent thereon are vague and indefinite in that it is not known what is meant by “terminated” in the definition of R4.
Claim 1 and claims dependent thereon are vague and indefinite in that it is not known what is meant by the C1 alkenylaryl or C1 alkenylheteroaryl in the definitions of R4 and R6.
Regarding claim 7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 9 is vague and indefinite in that it is not known what is meant by an optionally substituted H atom in the definition of R6.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation optionally substituted, and the claim also recites more preferably terminated which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 24 is vague and indefinite in that it is not known what is meant by “relevant preceding claims” with respect to the definitions of R1, R2, R3 and n for formula II; in the definitions of R4 and R5 for formula III; and in the definition of R4 for formula IIIa.
Claim 24 is vague and indefinite in that it is not known what is meant by the definition of R5 with respect to formula III where there is no R5 in formula III.
Claim 24 recites the limitation "formula I" in step (iii). There is insufficient antecedent basis for this limitation in the claim.
Claim 27 recites the limitation "the disease" in (i) and the second occurrence of (v). There is insufficient antecedent basis for this limitation in the claim.
Claim 27 recites the limitation "the viral tract infections" in (vi). There is insufficient antecedent basis for this limitation in the claim.
Claim Objections
Claims 28 and 29 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim must be stated in the alternative. See MPEP § 608.01(n).
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, 16-19 and 24-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 13, 16, 20, 23 and 27 of copending Application No. 17/912,284 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds, compositions, process of preparing and method of use of the compounds off formula (I) are embraced by the compounds, compositions, process of preparing and method of use of the compounds of formula I of 17/912,284 where n is 1, 2, 3 or 4.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H. Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624