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 1-20 are pending
Claims 10-16 is withdrawn from examination as being drawn to a nonelected invention/
Claims 1-9 and 17-20 are under consideration in the instant office action.
Election/Restrictions
Applicants’ election without traverse of group 1 (claims 1-9 and 17-20) and the following species in their response dated 9/24/2026 is acknowledged.
(1) one cholinesterase inhibitor from this list: huperzine A.
(2) one choline from this list: Acetyl L-carnitine.
(3) one carnitine from this list: alpha-glycerylphosphorylcholine.
(4) one muscarinic agonist from this list (for this one I do not have a
recommendation): pilocarpine.
From claim 2, Applicant elects, with traverse: Aqueous deficiency dry eye disease (ADDE),
Upon further consideration, the election of specie requirement is withdrawn. The restriction requirement remains. Claim 10-16 are withdrawn from examination as being drawn to a nonelected specie.
Claims 1-9 and 17-20 are under examination and the requirement for restriction is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/10/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application is a continuation of U.S. Application Serial No. 17/749,887 filed May 20, 2022, which claims priority to U.S. Provisional Application Serial No. 63/215,140, filed June 25, 2021
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-9 are rejected under 35 U.S.C. 103(a) as being unpatentable over Driscoll (US 2017/0326163) in view of Hamrah et al (US 2015/0038851) (both references are already of record)
Instant claims are drawn to a method for treating or preventing a disease or condition that causes dry eyes, neurological dry eye, or dry corneas comprising: identifying a patient in need of treatment or prevention of dry eyes, neurological dry eye, or dry corneas; and administering to the patient a composition comprising an effective amount of at least two active agents selected from: (1) at least one cholinesterase inhibitor; (2) at least one form of choline; (3) at least one form of carnitine; or (4) at least one form of muscarinic agonist, sufficient to treat the disease or condition that causes dry eyes, neurological dry eye, or dry corneas.
Driscoll teaches a method for treating or preventing a disease or condition that causes dry eyes (para [0010], [0018]), neurological dry eye, or dry corneas comprising: identifying a patient in need of treatment or prevention of dry eyes (para [0010]), neurological dry eye, or dry corneas; and administering to the patient a composition comprising an effective amount of at least two active agents selected from: (1) at least one cholinesterase inhibitor selected from: pyridostigmine, donepezil, tacrine, galantamine, and memantine, carbamates, physostigmine, neostigmine, ambenonlum, demecarium, rivastigmine, phenanthrene derivatives, galantamine, caffeine, rosmarinic acid, alphapinene, piperidines, tacrine, edrophonium, huperzine (para [0010]); (2) at least one form of choline selected from lecithin, choline chloride, choline bitartrate, acetylcholine, glycerophosphocholine, phosphatidylcholine, sphingomyelin, cytidine -diphosphocholine, or alpha-glycerylphosphorylcholine (para [0010]); (3) at least one form of carnitine selected from L-carnitine, Acetyl L-carnitine (para [0010]), or (4) at least one form of muscarinic agonist, selected from at least one of: acetylcholine, carbachol, methacholine, bethanechol, muscarine, pilocarpine, oxotriemorine, cevimeline, aceclidine, arecoline, AF102B, AF150(S), or AF267B sufficient to treat the disease or condition that causes dry eyes (para [0010], [0018]), neurological dry eye, or dry corneas. Driscoll teaches wherein the disease or condition is selected from Keratoconjunctivitis sicca (para [0010]), Aqueous deficiency dry eye disease (ADDE), allergies (para [0010]), Sjogren's syndrome (para [0010]), Evaporative Dry Eye (EDE), Vitamin A deficiency (para [0010]), blepharitis (para [0010]), meibomian gland disease (para [0010]), allergic conjunctivitis (para [0010]), pterygium (para [0010]), ocular symptoms of graft versus host disease (para [0010]), ocular allergy (para [0010]), atopic keratoconjunctivitis (para [0010]), vernal keratoconjunctivitis (para [0010]), uveitis (para [0010]), anterior uveitis (para [0010]), Bechet's disease (para [0010]), Steven Johnson syndrome (para [0010]), ocular cicatricial pemphigoid (para [0010]). chronic ocular surface inflammation caused by viral infection (para [0010]), herpes simplex keratitis (para [0010]), ocular rosacea (para [0010]), pinguecula (para [0010]), dry eyes associated with refractive surgery (para [0010]) or ocular surgeries, due to damage to the pre-or post-ganglionic lacrimal nerve, associated with connective tissue disorders, in conjunction with chronic inflammatory conditions such as eosinophilic disorders. wherein the dry eyes are caused by at least one of: tear film instability (para [0010], the composition improves tear film break-up time), hyperosmolarity of tears, ocular surface inflammation (para [0010]), corneal damage, neurosensory abnormalities (para [0105], hallucinations); increased ocular pain and sensitization, and neuropathic pain (para [0017], fibromyalgia); or are related to sex, gender, hormones, effects of sex steroids, hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 (para [0033], IGF-1), thyroid hormones, sex-related dry eyes including differences in parent-of-origin effects, X-chromosome gene dosage (X-inactivation), genes in the non-recombing region of the Y-chromosome, sex-specific autosomal factors, and epigenetics. They also disclose herein the disease or condition is a Dry Eye Disease (DED) selected from: meibomian gland dysfunction (MGD) related Dry Eye Disease (MDG-DED) (para [0010], melbomian gland disease), MGD-DED with tear film lipid layer deficiency, DED with a secondary evaporative element, DED due to blocking of the sensory drive to a lacrimal gland, DED due to trauma including, DED due to ocular or orbital surgery, or DED due to laser surgery, or DED due to LASIX surgery; or wherein the Dry Eye Disease (DED) is a genetic and/or acquired disorders of collagen (Ehlers-Danlos syndrome, Marfan's syndrome, Loeys-Dietz syndrome, Stickler syndrome, fibrillin disorders, elastin disorders, Joint Hypermobility Syndrome) (para [0030]), chronic infectious and/or fatigue syndrome including Chronic Fatigue Syndrome (para [0017]), COVID "Longhaulers" or Post-Acute Sequelae of SARS-CoV-2, Myalgic Encephalomyelitis, Post-Traumatic Stress Disorder, mild traumatic brain injury, Chronic Lyme disease, fibromyalgia (para [0017]); autoimmune disorders which may include multiple sclerosis, a vascular disease and a rheumatological disease; or wherein the DED is iatrogenic, and the active agent is selected from: antihistamines, beta-blockers, antispasmodics, diuretics, some psychotropic drugs, cis- retinoic acid, polychlorinated biphenyls; skin disorders, acne rosacea, atopic dermatitis, seborrheic dermatitis, psoriasis, cicatricial conjunctival diseases such as trachoma, erythema multiforme and pemphigoid; or wherein the dry eyes are associated with at least one of: Postural Orthostatic Tachycardia Syndrome ("POTS") (para [0105]), post-viral and post-infective autonomic dysfunction, chronic dry eyes (para [0030]), visual snow (para [0029]), and idiopathic dysautonomia (disorders of the autonomic nervous system) (para [0020]), traumatic brain injury (TBI), Post Traumatic Stress Disorder (PTSD), post-infectious Postural Orthostatic Tachycardia Syndrome, inflammatory autonomic dysfunction and Inflammatory Postural Orthostatic Tachycardia Syndrome, genetic disorders of RCCX, CYP21A2, disorders of the TGF-beta cascade, TNX, SMAD), autoimmune disorders (para [0020]), abnormal hormones (androgens and estrogens), genetic disorders of tryptase (including hereditary alpha tryptasemia), Hyper IgE Syndrome, low immune system (low IgG, low IgA), Idiopathic Intracranial Hypertension (IIH), vascular oxidation (including that due to hemochromatosis and hemolysis), low nitric oxide (para [0018]), impaired release of acetylcholine, genetic disorders of the acetylcholine manufacturing cycle. Driscoll discloses use of lecithin at 100 mg to 3 grams and 5 mcg to 300 mcg of Huperzine A; which amounts to 0.075 to 0.3 mg); 50 mg to 600 mg of Acetyl-L-Carnitine (para[0010], at least one of an antioxidant,10-180 mg of thiamin or magnesium (para [0010]), They further disclose that the range per dose is 30, 40, 50, 60, 70, 80, 90, 100, 150, 250, 270, 300, 350, 400, 450, 500, 540, 600, 700, 750, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,100, 2,200, 2,300, 2,400, 2,500, 2,600, 2,700, 2,800, 2,900, 3,000, 30 to 2,400, 40 to 2,300, 50 to 2,000, 60 to 1,500, 70 to 1,000, 80 to 750, 90 to 2,400, 200 to 2,300, 300 to 2,200, 400 to 2,100, 500 to 2,000, 600 to 1,900, 700 to 1,800, 800 to 1,700, 900 to 1,600, 1,000 to 1,500, 1,100 to 1,400, 1,200 to 1,300, of the choline compound. In another aspect, the range per dose is 75, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 75 to 300, 80 to 275, 90 to 250, 100 to 225, 125 to 200, 150 to 175 mcg of huperzine A. In another aspect, the range per dose is 50, 75, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 50 to 600, 75 to 600, 80 to 575, 90 to 550, 100 to 525, 125 to 500, 150 to 475, 175 to 450, 200 to 425, 225 to 400, 250 to 375, 275 to 350, 300 to 325 Acetyl-L-Carnitine. In another aspect, the range per dose is 10, 20, 30, 40, 50, 60 mg Thiamin. In another aspect, the range per dose is 0.3, 0.5, 0.75, 1.0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 mg Magnesium.(para [2010]).Driscoll discloses wherein the composition is adapted to be administered prenatally, orally, intravenously, intraperitoneally, intranasally, intrapulmonary, subcutaneously, intracutaneously, or intramuscularly (para [0010])
Driscoll fails to disclose limitations wherein the method comprising at least one of: obtaining a cell sample that is examined for an increase in inflammatory cells in the conjunctiva; or measuring pupil size before and after administration of the composition, wherein above-average pupil size that becomes smaller with treatment of the compound is diagnostic of neurological dry ; wherein the symptoms and signs of dry eyes and low tear production by either acinar cells of the lacrimal gland or cells of meibomian glands as determined by at least one of: tear film instability, hyperosmolarity of tears, ocular surface inflammation, corneal damage, neurosensory abnormalities; increased ocular pain and sensitization, neuropathic pain, light sensitivity, decreased accommodation, fluctuating vision, pupils that are larger than average.
However, Hamrah et al. teaches a method for diagnosing dry eye associated with meibomian gland dysfunction (para [0026]-[0027]) comprising: obtaining a cell sample that is examined (para [0153], in vivo confocal microscopy study of eyelid tissues) for an increase in inflammatory cells in the conjunctiva (para [0096], [0154]-[0164]). It would have been obvious to one of ordinary skill in the art to combine the teachings of Driscoll and Hamrah et al., as both are directed to the treatment of dry eye caused by meibomian gland dysfunction, and include the diagnostic steps disclosed in Hamrah et al. in the method of Driscoll, in order to provide patient-appropriate treatment for dry eye in a subject (Driscoll, para [0030]).
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Driscoll and Hamrah et al. Both teach the instantly claimed method and compositions comprising the same agents,. As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in treating or preventing disease or conditions which cause dry eyes, with the instantly claimed composition, absence of evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 or U.S. Patents: 12,042,503 (‘503)
Instant claims are drawn to a method for treating at least one of chronic dry eye prior to damage to a lacrimal gland, neurological dry eye, or dry corneas, comprising: obtaining a sample from the palpebral conjunctiva of a patient; staining the sample to detect inflammatory cells; and determining that the patient has neurologic dry eyes due to the presence of inflammatory cells near the lacrimal nerve, wherein epithelial cells in the palpebral conjunctiva have a normal nucleus to cytoplasm ratio, and wherein the inflammatory cells cause a lacrimal nerve insufficiency that causes the chronic dry eyes; wherein if the patient has lacrimal nerve insufficiency, administering to the patient a composition comprising an effective amount of at least two active agents selected from: (1) at least one cholinesterase inhibitor; (2) at least one form of choline; (3) at least one form of carnitine; or (4) at least one form of muscarinic agonist, sufficient to treat the disease or condition that causes dry eyes.
Claims 1-3 of ‘503 are drawn to a method for using conjunctival cytology of a patient suspected to detect neurologic chronic dry eye prior to damage to a lacrimal gland, comprising: obtaining a sample from the palpebral conjunctiva; staining the sample to detect inflammatory cells; and determining that the patient has neurologic dry eyes due to the presence of inflammatory cells near the lacrimal nerve, wherein epithelial cells in the palpebral conjunctiva have a normal nucleus to cytoplasm ratio, and wherein the inflammatory cells cause a lacrimal nerve insufficiency that causes the chronic dr
While the two sets of claims are not identical, they are both drawn to the method which includes the steps of obtaining a sample from the palpebral conjunctiva of a patient; staining the sample to detect inflammatory cells; and determining that the patient has neurologic dry eyes due to the presence of inflammatory cells near the lacrimal nerve, wherein epithelial cells in the palpebral conjunctiva have a normal nucleus to cytoplasm ratio, and wherein the inflammatory cells cause a lacrimal nerve insufficiency that causes the chronic dry eyes; wherein if the patient has lacrimal nerve insufficiency, administering to the patient a composition comprising an effective amount of at least two active agents selected from: (1) at least one cholinesterase inhibitor; (2) at least one form of choline; (3) at least one form of carnitine; or (4) at least one form of muscarinic agonist, sufficient to treat the disease or condition that causes dry eyes. Therefore, subject matter disclosed in instant claims of the instant application are fully taught in claim 1-9 of the parent patent ‘503 and hence renders the instant claims obvious.
Conclusion
Claims 1-9 and 17-20 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dierdre (Renee) Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
