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 1-3, 5-15 and 17-22 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 1-3, 5-15 and 17-22 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 of age-related macular degeneration, does not reasonably provide enablement for the prevention or treatment of any eye disease associated with retinal cell lipofuscin-associated cytotoxicity. 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.
The scope of claims 1-3, 5-15 and 17-22 are not adequately enabled solely based on the modulation of the activity of a lipofuscin-associated cytotoxicity or ABCA4 provided in the specification. Claims 1-3, 5-15 and 17-22 are the method for treating and eye disease, which is not remotely enabled. The scope of claims 1-3, 5-15 and 17-22 includes diseases and/or conditions not even known at this time, which may be associated with retinal cell lipofuscin-associated cytotoxicity. While the treatment of age-related macular degeneration has been linked with retinal cell lipofuscin-associated cytotoxicity activity the art does not recognize use of such inhibitors as broad-based drugs for treating all disorders instantly embraced. Additionally, instant claim language embraces disorders not only for treatment but also for the prevention, which is not remotely enabled.
In addition, claims 1-3, 5-15 and 17-22 embraces any and all eye disease. The scope of the method claims is not adequately enabled solely based on the retinal cell lipofuscin-associated cytotoxicity provided in the specification.
The scope of "eye disease” cannot be deemed enabled. The term "eye disease” covers a broad array of different disorders that have different modes of action and different origins.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed more recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
With regard to enablement of a claim drawn generally to treatment of impairment of a body organ’s functions, see In re Schmidt, 153 USPQ 640, 653.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) Breadth of claims.
(a) Scope of the compounds.
(b) Scope of the diseases covered. Disorders of the eye have a vast range.
Eye inflammations include scleritis and episcleritis, inflammation of tissues on the sclera, which includes syphilitic episcleritis, tuberculous episcleritis and zoster scleritis.
Iridocyclitis, inflammation of the iris and the ciliary body comes in numerous forms. Chronic iridocyclitis is most commonly secondary to diseases such as ankylosing spondylitis, Behçet's syndrome, inflammatory bowel disease, juvenile rheumatoid arthritis, Reiter's syndrome, sarcoidosis, syphilis, tuberculosis, and Lyme disease. There are also acute or recurrent forms, along with lens-induced iridocyclitis. It can be granulomatous or non-granulomatous.
Inflammation of lacrimal passages includes acute dacryocystitis (caused by staphylococci or streptococci), dacryopericystitis, acute lacrimal canaliculitis, chronic dacryocystitis, chronic lacrimal canaliculitis and mucocele.
Inflammation of the orbit includes abscess of the orbit, orbital cellulitis, osteomyelitis of the orbit, orbital periostitis, tendonitis and granuloma of orbit.
Chorioretinal inflammations are varied. There is focal chorioretinitis, focal choroiditis (including multifocal choroiditis and panuveitis (MCP)), focal retinitis and focal retinochoroiditis. These four also exist in a disseminated form. There is also Posterior cyclitis, e.g. pars planitis. Also included is Vogt-Koyanagi-Harada syndrome (Harada's disease), an acute inflammatory, immune-mediated disorder that can cause choroidal neovascularization, severe chorioretinal atrophy, and secondary glaucoma. There are infective forms of chorioretinitis, notably syphilitic, tuberculous, and toxoplasmic. Other forms include albuminuric retinitis and renal retinitis.
There is also a wide assortment of forms of conjunctivitis, including seasonal allergic conjunctivitis, perennial allergic conjunctivitis, and giant papillary conjunctivitis (GPC) (a chronic yet poorly condition associated with contact lens wear). In addition to types of allergic conjunctivitis there is also bacterial conjunctivitis (e.g. from Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) and viral conjunctivitis (e.g. from gonorrhea, herpes simplex, chlamydia, adenoviruses or enteroviruses) Parasitic conjunctivitis (e.g. from Onchocerca volvulus, Loa loa, Wuchereria bancrofti or Trichinella spiralis), fungal conjunctivitis (e.g. from Candida albicans or Sporothrix schenckii), Phlyctenular Conjunctivitis, Inclusion Conjunctivitis, immunologic conjunctivitis, irritant or chemical conjunctivitis (e.g. from burns, chlorine or air pollutants), Radiation conjunctivitis, and assorted forms of neonatal conjunctivitis (which can be caused by e.g. a blocked tear duct). Also included are mucopurulent conjunctivitis and blepharoconjunctivitis.
Cataract disorders include senile incipient cataract (which can be coronary, cortical, or punctate), and also includes subcapsular polar senile cataract (which can be anterior or posterior). Senile nuclear cataract includes cataracta brunescens and sclerosis cataract. There is also morgagnian type senile cataract, including senile hypermature cataract, and some combined forms.
Non-senile cataract forms include infantile, juvenile and presenile cataracts, traumatic cataract, and the so-called “Complicated cataract”, which includes glaucomatous flecks (subcapsular), cataract in chronic iridocyclitis, and cataract secondary to ocular disorders. There are also drug-induced cataracts, Soemmerring's ring and assorted secondary cataracts. That latter category includes myotonic cataract, diabetic cataract and cataract in other endocrine, nutritional and metabolic diseases, such as malnutrition-dehydration cataract and cataract in hypoparathyroidism.
Other lens disorders include congenital lens malformations, mechanical complications of intraocular lens, aphakia and pseudophakia and any form of dislocation of the lens.
Keratitis comes in diverse forms. The corneal ulcers can be central, marginal, perforated, ring, with hypopyon or NOS. There is also the related Mooren ulcer. Form of superficial keratitis without conjunctivitis include keratitis itself, which can be areolar, filamentary, nummular, stellate, striate or superficial punctate. There is also photokeratitis which includes corneal flash burns and snow blindness.
Keratoconjunctivitis includes vernal keratoconjunctivitis and atopic keratoconjunctivitis, both allergic forms, as well as exposure keratoconjunctivitis, neurotrophic keratoconjunctivitis, and phlyctenular keratoconjunctivitis. There is also Keratoconjunctivitis sicca, which comes in two forms: Aqueous tear-deficient keratoconjunctivitis sicca (caused by inadequate tear volume) and evaporative keratoconjunctivitis sicca (caused by poor tear quality). Ophthalmia nodosa and superficial keratitis with conjunctivitis is generally classified here. Other forms of keratitis include feline eosinophilic keratitis and interstitial Keratitis (Parenchymatous Keratitis, aka deep keratitis), and a variant form, Cogan's syndrome. There are also numerous forms of pathogenic keratitis, Including Amoebic keratitis, bacterial keratitis (including Contact lens acute red eye (CLARE)), fungal keratitis, herpes simplex keratitis (dendritic keratitis), and herpes zoster keratitis. River blindness arises from inflammation of the eye caused by larvae (microfilaria) of the nematode Onchocerca volvulus (hence onchocercal keratitis), although the Wolbachia bacteria, carried by the nematode, may be involved as well.
Corneal neovascularization, commonly arising from contact lens wear includes ghost vessels and pannus. There are assorted forms of Corneal scars and opacities, including adherent leukoma and central corneal opacity, and corneal clouding from Scheie syndrome (which arises from the metabolic disorder Mucopolysaccharidosis I).
Corneal pigmentations and deposits include haematocornea, Kayser-Fleischer ring, Krukenberg's spindle and Staehli's line.
The corneal deformities include corneal ectasia, corneal staphyloma, descemetocele, and keratoconus (an increasingly conical shape to the cornea).
Other Corneal problems include Bullous keratopathy; a fold or rupture in Descemet's membrane; types of corneal degeneration, especially arcus senilis and band keratopathy. There are also forms of hereditary corneal dystrophies, which can be epithelial, granular, lattice and macular. Fuchs’ endothelial dystrophy is included with this. There is also anaesthesia of the cornea, hypaesthesia of the cornea, and recurrent erosion of the cornea.
Degeneration of iris and ciliary body include iridoschisis, iris atrophy (which can be essential or progressive), miotic pupillary cyst, and translucency of iris. There is also pigmentary degeneration of the iris and degeneration of the pupillary margin.
There are cysts of the iris, ciliary body or anterior chamber, which can be exudative or parasitic, there are implantation cysts and the miotic pupillary cyst.
Adhesions and disruptions of the pupillary membranes, iris and ciliary body include iris bombé, pupillary occlusion, pupillary seclusion, goniosynechiae, iridodialysis, chamber angle recession, corectopia, and synechiae of the iris, which can be anterior or posterior.
Other disorders of iris and ciliary body include hyphaema, neovascularization of iris or ciliary body, rubeosis of iris.
Disorders of conjunctiva (other than the conjunctivitis listed above) include the conjunctival degenerations and deposits, including conjunctival argyrosis (argyria), concretions, pigmentation and xerosis NOS. There are also conjunctival scars (symblepharon), conjunctival haemorrhage (includeing subconjunctival hemorrhage), conjunctival aneurysms, conjunctival hyperaemia, conjunctival edemas, pterygium and pseudopterygium.
Disorders of lacrimal system, aside from inflammation of lacrimal passages mentioned above, include dacryoadenitis, chronic enlargement of lacrimal gland, dacryops, dry eye syndrome, lacrimal cyst, lacrimal gland atrophy, epiphora, and lacrimal fistula. Stenosis and insufficiency of lacrimal passages includes dacryolith, eversion of lacrimal punctum, and stenosis of lacrimal canaliculi, ducts and sacs. There are also assorted congenital malformations of lacrimal system.
Disorders of the orbit, other than inflammations listed above, include orbital haemorrhage, oedema of the orbit, cyst of orbit, Enophthalmos, echinococcus infection of orbit, myiasis of orbit and dysthyroid exophthalmos. Deformities of the orbit include atrophy and exostosis of the orbit.
Disorders of the choroid and retina, other than the chorioretinal inflammation discussed above, include horioretinal scars, such as macula scars of posterior pole post-traumatic) and solar retinopathy, forms of choroidal degeneration (which include atrophy and sclerosis of choroid as well as angioid streaks), Choroidal haemorrhage, choroidal detachment, and assorted hereditary choroidal dystrophies, such as ornithinaemia, choroideremia, choroidal dystrophy, (which can be central areolar, generalized or peripapillary) and choroid gyrate atrophy.
There are a variety of retinal detachments and breaks. These include detachment of retinal pigment epithelium, rhegmatogenous retinal detachment, serous retinal detachment, central serous chorioretinopathy, and proliferative vitreo-retinopathy with retinal detachment. Retinal breaks without detachment include horseshoe tear of retina and round hole of retina, both without detachment.
There are also chorioretinal scars after surgery for detachment, and peripheral retinal degeneration without break. There is also tractional retinal detachment.
Retinal cysts include cyst of ora serrata, parasitic cyst of retina, pseudocyst of retina, and microcystoid degeneration of retina.
Retinoschisis can be hereditary, as in X linked juvenile retinoschisis and familial foveal retinoschisis, or degenerative, either in typical or reticular form, can be tractional, or can be exudative, often secondary to optic disc pit.
Retinal vascular occlusions include the vein occlusions, which can be central, incipient, partial, or tributary. There is also amaurosis fugax, transient retinal artery occlusion, central retinal artery occlusion, Hollenhorst's plaque, retinal microembolisms, and retinal artery occlusions, which can be branched or partial.
Changes in retinal vascular appearance include retinal micro-aneurysms, neovascularization, perivasculitis, varices, vascular sheathing and retinal vasculitis.
Also included are the microvascular abnormalities of the retina, which would cover diabetic retinopathy (which includes both nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)), retinopathy of prematurity, retinal hemorrhages (including the blot and flame-shaped hemorrhages), microaneurysms, arteriovenous nicking, focal arteriolar narrowing, arteriolar wall thickening, and Cotton wool spots (soft exudates).
Macular degeneration is a general category of retinal diseases which vary according to both a-wave and b-wave electrophysiology, dark adapted sensitivity, and bleaching adaptation. The most common category is age-related macular degeneration, which comes as neovascular or exudative AMD, the “wet” form, and as Central geographic atrophy, the “dry” form of AMD. The second type is juvenile macular degeneration, which includes Stargardt’s disease (fundus flavimaculatus), Best’s Disease (vitelliform dystrophy), Doyne's Disease (honeycomb retinal dystrophy), Malattia levintinese, Sorsby’s Disease (fundus dystrophy), and Autosomal dominant hemorrhagic macular dystrophy. A third group are the pattern dystrophies such as vitreoretinochoroidopathy, adult onset foveomacular vitelliform dystrophy (AOFVD), fundus pulverulentus, butterfly-shaped pigment dystrophy, reticular dystrophy of the RPE, and multifocal pattern dystrophy simulating fundus flavimaculatus. Cone-rod dystrophy is generally taken as a form of macular degeneration, although it must be noted that some consider only AMD to be a true macular degeneration, and the other disorders sufficiently different that they should not be included. Other retinal dystrophies sometimes included here are the albipunctate, pigmentary, vitelliform, tapetoretinal, and vitreoretinal retinal dystrophies as well as retinitis pigmentosa, which exists in dozens of forms depending on which defective gene is involved.
In addition to those, other degenerations of macula and posterior pole include macular cysts, hole of macula, degenerative drusen, and puckering of macula, along with Kuhnt-Junius degeneration and toxic maculopathy.
Other retinal disorders include atherosclerotic retinopathy, Coats retinopathy, exudative retinopathy, proliferative sickle-cell retinopathy, hypertensive retinopathy, retrolental fibroplasia, Proliferative vitreo-retinopathy. There are Peripheral retinal degenerations which can be, lattice, microcystoid, palisade, paving stone or reticular. There is also retinal dystrophy arising from lipid storage disorders.
Glaucoma comes in several forms. Angle-closure glaucoma can be acute chronic, or intermittent. Primary open-angle glaucoma can be capsular with pseudoexfoliation of lens, chronic simple, low-tension or pigmentary. There is also Ocular hypertension, absolute glaucoma, congenital glaucoma and forms of traumatic glaucoma due to birth injury, eye inflammation or other eye disorders, or to drugs.
Disorders of the vitreous body include vitreous prolapse, vitreous syndrome following cataract surgery, vitreous haemorrhage, crystalline deposits in vitreous body, vitreous membranes and strands, vitreous degeneration and vitreous detachment. Some of these give rise to “floaters”.
Disorders of the globe of the eye, or bulbus oculi, include forms of endophthalmitis, especially panophthalmitis, vitreous abscess, parasitic endophthalmitis and sympathetic uveitis. Degenerative disorders of globe include chalcosis, siderosis of eye, atrophy of globe, phthisis bulbi and degenerative myopia. There is also hypotony of eye, haemophthalmos, and luxation of globe, which can generally be included here.
Disorders of the eye incudes color vision deficiencies, including achromatopsia, acquired color vision deficiency, color blindness in many forms, deuteranomaly, deuteranopia, protanomaly, protanopia, tritanomaly and tritanopia. Subjective visual disturbances include asthenopia, day blindness, hemeralopia, metamorphopsia, photophobia, scintillating scotoma, sudden visual loss, and visual halos. There is also amblyopia, which can be anisometropic, deprivation, or strabismic, as well as diplopia (double vision).
Binocular vision disorders include abnormal retinal correspondence, fusion with defective stereopsis, simultaneous visual perception without fusion, and suppression of binocular vision. Visual field defects include enlarged blind spot, generalized contraction of visual field, hemianop(s)ia (which can be heteronymous or homonymous), and quadrant anop(s)ia. There are also scotoma, which can be arcuate, Bjerrum, central or ring.
There are a number of forms of night blindness, including Congenital Stationary Night Blindness (which exists in three forms, autosomal dominant, autosomal recessive, and X-linked), Oguchi's disease, and others. It also includes general visual impairment up to complete blindness. That is, the claims embrace restoring vision to one who is totally blind.
Postprocedural disorders of the eye include bleb associated endophthalmitis, chorioretinal scars after surgery for detachment, inflammation (infection) of postprocedural bleb, postprocedural blebitis, vitreous (touch) syndrome and vitreal corneal syndrome (the latter two arising from cataract surgery)
It includes various forms of Ocular Albinism, including X-linked ocular albinism, autosomal recessive albinism, Aland Island Eye Disease, and about a dozen different forms of Oculocutaneous Albinism.
Cancer of the eye depends very much on which structure of the eye or its adnexa is involved. Choroidal tumors include choroidal melanoma, ciliary body melanoma choroidal osteoma and metastatic choroidal tumors, including tumors from the lung, breast, prostate, kidney, thyroid and blood. Iris tumors include iris melanoma, malignant iris melanocytoma, and anterior uveal metastasis, most commonly from breast, lung, prostate, skin, kidney, colon and thyroid. Retinal tumors include retinal pigment epithelium tumors, and retinoblastoma. Conjunctival tumors are quite varied, and include conjunctival kaposi's sarcoma, epibulbar dermoid, lymphoma of the conjunctiva, pigmented conjunctival tumors (a malignant melanoma), and squamous carcinoma (including intraepithelial neoplasia of the conjunctiva). Infiltrative intraocular tumors include chronic lymphocytic leukemia, infiltrative choroidopathy and intraocular lymphoma. Orbital tumors include adenoid cystic carcinoma of the lacrimal gland, lymphangioma of the orbit, orbital pseudotumor, and orbital rhabdomyosarcoma.
There are numerous forms of strabismus. The category of paralytic strabismus has the Third [oculomotor] nerve palsy, fourth [trochlear] nerve palsy, and sixth [abducent] nerve palsy (aka Abducens Nerve Palsy). This also includes the ophthalmoplegia: total (external) ophthalmoplegia, progressive external ophthalmoplegia, and progressive supranuclear ophthalmoplegia. Kearns-Sayre syndrome, Superior oblique palsy and Double Elevator Palsy are also included here.
The non-paralytic forms of include convergent concomitant strabismus, include the esotropias, which can be alternating or monocular, and which comes in numerous forms: Congenital, acquired, Accommodative, infantile, “Esotropia with High AC/A Ratio”, and pseudoesotropia.
There is also divergent concomitant strabismus, including exotropia (again, alternating or monocular), vertical strabismus (both hypertropia and hypotropia), intermittent esotropia, intermittent exotropia (again, alternating or monocular), concomitant strabismus, cyclotropia, microtropia, monofixation syndrome, alternating hyperphoria, esophoria, and exophoria.
There is also mechanical strabismus, which covers Brown's sheath syndrome, strabismus due to adhesions, and traumatic limitation of duction of eye muscle. Duane's syndrome, Brown’s Syndrome, Mobius Syndrome, and Congenital Fibrosis Syndrome are also classified as a strabismus.
Asides from the strabismuses, there are some other disorders of binocular movement, notably Palsy of conjugate gaze, Convergence insufficiency and excess and Internuclear ophthalmoplegia. Other Oculomotor deficiencies include Athabaskan Brainstem Dysgenesis Syndrome (ABDS) and Bosley-Salih-Alorainy syndrome. There is also a form of hypometric saccades arising from Ataxia-telangiectasia, an autosomal recessive genetic disorder.
There are a number of disorders of refraction and accommodation. Hyperopia (farsightedness, or hypermetropia) is generally classified into three types: simple hyperopia, pathological hyperopia and functional hyperopia. Myopia (nearsightedness) takes a range of clinical forms: simple myopia, degenerative myopia (malignant, or progressive myopia), nocturnal myopia, pseudomyopia, induced myopia (acquired myopia), index myopia, form deprivation myopia and nearwork-induced transient myopia. Forms of astigmatism can be classified on the axis of the principal meridians, giving with-the-rule astigmatism, against-the-rule astigmatism, oblique astigmatism and irregular astigmatism.
Anisometropia is the condition in which the two eyes have unequal refractive power; one may be nearsighted and the other farsighted.
Aniseikonia is an ocular condition where there is a significant difference in the perceived size of images. It can occur as an overall difference between the two eyes, or as a difference in a particular meridian. It can arise naturally, e.g. caused by aphakia, or be a consequence of a refractive error in eyeglasses.
Other disorders of disorders of refraction and accommodation include presbyopia, spasm of accommodation, paresis of accommodation and internal ophthalmoplegia.
Other eye disorders include ocular pemphigoid, equatorial staphyloma and scleral ectasia, nystagmus, ocular pain, occlusion of the central retinal vein, retinal ischemia, angiospasms of retinal arterioles, dilation of retinal veins, ocular-retinal developmental disease, papilledema, compressive optic neuropathy, Stevens-Johnson syndrome (SJS, a immune-complex–mediated hypersensitivity disorder caused by many drugs, viral infections, and malignancies and is often of unknown origin), retrolental fibroplasia, Cone and Cone-Rod Dystrophies (which come in a variety of different genetic forms, all untreatable), Usher syndrome (which exists in three separate forms, US1, US2 and US3), Bardet-Biedl syndrome (BBS), (an untreatable collection of inherited retinal degenerative diseases), nonarteritic ischemic optic neuropathy (NAION), superior oblique myokymia and many other problems.
The above listing does not include disorders of the eyelids, eyelashes or eyebrows, or of the optic nerve, as it is not clear if these are actual intended.
(2) The nature of the invention and predictability in the art: The invention is directed toward 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).
(3) Direction or Guidance: That provided is very limited. The dosage range information in paragraph [0094] ranges from 0.01 to 1000 mg per kg of body weight per day. 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 treating an eye disease.
(4) State of the Prior Art: These compounds are dabrafenib, necrosulfonamide, arimoclomol, KIRA3, KIRA6, KIRA7, KIRA8, salubrinal, SAL003 and necrostatin 7. So far as the examiner is aware, no compounds selected for the group consisting of dabrafenib, necrosulfonamide, arimoclomol, KIRA3, KIRA6, KIRA7, KIRA8, salubrinal, SAL003 and necrostatin 7 of any kind have been used for the treatment of eye diseases in general.
(5) Working Examples: there are only 7 examples
(6) Skill of those in the art:
Those of ordinary skill in the art know that the majority of eye problems tend to be untreatable with pharmaceuticals, or are treated only by dealing with the underlying cause itself. There are a very wide range of causes for eye problems, For example, many diseases and disorders can lead to optic atrophy. These includes hereditary disorders (Leber's hereditary optic neuropathy), infectious diseases (syphilis), metabolic disorders such as hyperthyroidism (Graves' disease). Optic atrophy can arise when the optic nerve or nerves did not develop properly. It may also result from inflammation of the optic nerve or from glaucoma. In other cases, poisons (e.g. cyanide, lead, and carbon monoxide), vitamin deficiencies, or tumors (which causes Compressive optic neuropathy) may be responsible. Type II diabetes causes NPDR and PDR. NAION, which is the leading cause of sudden vision loss in people over 50, arises from blockage of blood to the optic nerve, and there is no approved pharmacological treatment. Autoimmune disorders are responsible for some retinopathies, e.g. Behçet's disease commonly causes Uveitis. The pattern dystrophies and all forms of juvenile macular degeneration are considered untreatable by pharmaceuticals, and there is no generally recognized as effective pharmacological treatment for AMD.
Some are of unknown origin and have no pharmaceutical treatment, e.g. keratoconus. Most commonly, optic atrophy is idiopathic. Orbital cellulitis, which can be life-threatening infections, usually arise from staphylococcus. Hence, these types of inflammations are treated with intravenous antibiotics.
There is no pharmacological treatment for drusen, pterygium or for Leber's Congenital Amaurosis. No form of strabismus or any other ocular muscle disorders can be treated with pharmaceuticals. Nor can disorders of refraction and accommodation. This is of no small significance, since disorders of refraction and accommodation as a class are the most common form of eye problems.
(7) The quantity of experimentation needed: Because of factors 1b, 6, this is expected to be substantial and undue.
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.
It is difficult to treat many of the disorders claimed herein. Instant claim language embraces disorders not only for treatment but the prevention, which is not remotely enabled. It is presumed in the prevention of the diseases and/or disorders claimed herein there is a way of identifying those people who may autosomal recessive retinitis pigmentosa (RP), Stargardt disease (STGD), Best disease (BD), cone-rod dystrophy, or ABCA4 mutant Age-Related Macular Degeneration (AMD), etc. There is no evidence of record, which would enable the skilled artisan in the identification of the people who have the potential of becoming afflicted with the disorders claimed herein.
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.
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 13-15 and 17-22 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:
Claim 13-15, 17, 19-21 and claims dependent thereon recite the limitation "Nec7" in list of compounds. There is insufficient antecedent basis for this limitation in the claim.
The term “an agent” in claim 21 is a relative term, which renders the claim indefinite. The term “an agent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The nature of the composition consisting of the compounds of formula I and an additional active ingredient, which is an agent.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 8, 13, 17, 18, 20 and 21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Backes et al., WO 2014/052669. Backes teaches the compounds KIRA3 and KIRA6 as set forth in Paragraph [0296] for the treatment of eye diseases, such as retinitis pigmentosa and macular degeneration. The generic structure of Backes encompasses the instantly claimed method of use of the compounds KIRA7 as claimed herein. Paragraph [0296] on page 97 differs only in the nature of the R2 substituent of the imidazopyrazine ring of formula (I). Paragraph [0272], lines 17-23, defines the substituent R2 as hydrogen, oxo, halogen, -CXa3, -CN, -SO2Cl, -SOn1R10a, -SOv1NR7aR8a, -NHNH2, -ONR7aR8a, -NHC=(O)NHNH2, -NHC=(O)NR7aR8a, -N(O)m1, -NR7aR8a, -C(O)R9a, -C(O)OR9a, -C(O)NR7aR8a, -OR10a, -NR7aSOn1R10a, -NR7aC=(O)R9a, -NR7aC(O)OR9a, -NR7aOR9a, -OCXa3, -OCHXa2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The compounds of the instant invention are generically embraced by Backes in view of the interchange ability of R2 substituents of the imidazopyrazine ring system. Thus, one of ordinary skill in the art at the time the invention was made would have been motivated to select for example 1-methylcycloprop-1-yl for the R2 substituent, i.e. KIRA7 of the reference as well as other possibilities from the generically disclosed alternatives of the reference and in so doing obtain the instant compounds in view of the equivalency teachings outlined above.
Claim(s) 1-3, 5-15 and 17-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pan et al., PNAS. Pan teaches the method of treating age-related macular degeneration, dry AMD, Stargardt disease, etc. with the therapeutic agent necrosulfonamide, Nec7 and arimoclomol as set forth in the significance box on page 1.
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624