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 .
Application Status
The original claim set filed on 4/04/2023 is acknowledged. Claims 1-20 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statement filed on 3/05/2023 has been considered except where lined through.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-4, 7-11 and 13-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Popova et al. (The Journal of Neuroscience, 2021; 41(31):6775-6792).
Popova et al. discusses the ability of epigenetic modifies to prevent degeneration of rod photoreceptors in a mouse model of retinitis pigmentosa (RP), using rd10 mice of both sexes, wherein inhibitors of (LSD1) and histone deacetylase blocked rod degeneration, preserved vision, and affected the expression of multiple genes including maintenance of rod-specific transcripts and downregulation of those involved in inflammation, gliosis, and cell death (Abstract). With regards to the epigenic modifiers (e.g. LSD1 and HDAC1 inhibitors), Popova et al. teach that mice were treated daily with intraperitoneal injections of TCP at 10 mg/kg, GSK2879552 at either 1.5 mg/kg or 4.2 mg/kg or romidepsin at 0.2 mg/kg, wherein all inhibitors were diluted in 0.9% bacteriostatic saline (page 6776, 2nd column, 2nd full paragraph). Moreover, Popova et al. teach that the rd10 mice were treated daily for 15 days (page 6778, 1st column, 1st full paragraph). Popova et al. further teach that the inhibitor specific for LSD1 alters retinal gene expression in rd10 mice. For example, Popova et al. teach expression of markers of infiltrating immune cells, such as monocytes and macrophages H2-Aa, cd74, and Cx3r1 were upregulated in rd10 and returned to normal levels of expression in ed10+GSK (page 6782, 2nd column, 2nd full paragraph). Furthermore, Popova et al. teach that expression of one group of rod-specific genes, Rho, Prph2, Nr2e3, Nrl and Pde6b was increased dramatically and reached WT levels with GSK treatment (page 6783, 1st column, 3rd full paragraph).
Claim(s) 1-4, 10, 13-17 and 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsutsumi et al. (Invest Ophthalmol Vis Sci. 2016; 57(14): 6461-6473).
Tsutsumi et al. teach potential neuroprotective effects of an LSD1 inhibitor in Retinal Ganglion cells via p38 MAPK activity (title). Specifically, Tsutsumi et al. teach that tranylcypromine significantly suppressed neuronal cell death following glutamate neurotoxicity and oxidative stress, wherein the intravitreal administration of tranylcypromine significantly saved RGC numbers in an in vivo glaucoma model in mice employing NMDA-induced excitotoxicity (Results). Thus, while the prior art does not specifically teach the “results” as claimed in claims 13-17 of administration of tranylcypromine, the claimed limitation does not appear to results in a patentable difference since the same compound is administered to a patient suffering from a retinal disorder, e.g. glaucoma. Applicants are reminded that the Office does not have the facilities and resources to determine that such a result will not occur. Burden is on Applicants to rebut such information. See MPEP 2112.01.
Claim(s) 1-2, 5-6, 9-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chakrabarti et al. (WO2022/006667A1, 2022-01-13).
Chakrabarti et al. teach a method of treating a condition, the method comprising administering to a subject in need thereof a therapeutically effective amount of at least one agent that inhibits at least one biological activity of the long non-coding RNA HOTAIR, wherein the condition includes, but is not limited, diabetic retinopathy, neovascular glaucoma, ischemic retinopathy, retinopathy secondary to retinal vein occlusion, and age-related macular degeneration, wherein the patient is a human (claims 11 and 20 of the WO). With regards to the agent, Chakrabarti et al. teach that the agent is a histone methylation inhibitor such as DZNep (claims 22 and 24 of the WO). Moreover, Chakrabarti et al. teach that the agent is administered in combination with another therapeutic agent such as an anti-VEGF agent (claim 41 of the WO). With regards to the administration, Chakrabarti et al. teach that the routes of administration of the agents include, but are not limited to, intravitreal administration, wherein administration occurs for an extended period to time including at least 2 weeks (page 69, lines 10-12 and 19-22). Lastly, Chakrabarti et al. pharmaceutical composition comprising the agents and a pharmaceutically acceptable carrier/excipients such as water and sodium chloride (page 67, lines 7-21). Thus, while the prior art does not specifically teach the “results” as claimed in claims 13-17 of administration of DZNep, the claimed limitation does not appear to results in a patentable difference since the same compound is administered to a patient suffering from a retinal disorder. Applicants are reminded that the Office does not have the facilities and resources to determine that such a result will not occur. Burden is on Applicants to rebut such information. See MPEP 2112.01.
Claim(s) 1-2, 7-8 and 10-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gulab Zode (WO2018/013568A1, 2018-01-18) referred to herein as Zode.
Zode teaches a method of treating an eye disease in a subject in need thereof an effective amount of a mTOR inhibitor in combination with a histone deacetylate inhibitor such as Romidepsin in a synergistic amount to treat the eye disease (claim 17, 29 and 31 of the WO). With regards to the eye disease the includes, but is not limited to, age-related macular degeneration and diabetic retinopathy (page 2, lines 4-5). With regards to the administration, the WO document teaches that routes of administration include, but are not limited to, intravitreal, intraocular and ocular administration, wherein the composition is administered in an admixture with suitable pharmaceutical salts, buffers, diluents, extenders, excipients and/or carriers (page 9, lines 24-25). Thus, while the prior art does not specifically teach the “results” as claimed in claims 13-17 of administration of Romidepsin, the claimed limitation does not appear to results in a patentable difference since the same compound is administered to a patient suffering from a retinal disorder. Applicants are reminded that the Office does not have the facilities and resources to determine that such a result will not occur. Burden is on Applicants to rebut such information. See MPEP 2112.01.
Claim(s) 1-2, 7-9 and 13-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clemson et al. (Br. J. Ophthalmol 2011; 95: 89-93, IDS).
Clemson et al. teach the therapeutic potential of valproic acid for retinitis pigmentosa (Title). With regards to valproic acid, Clemson et al. teach that valproic acid is a potent inhibitor of histone deacetylase (HDAC) (page 89, 1st column, 2nd full paragraph). In particular, Clemson et al. discloses that valproic acid was administered at a dose of 500 to 750mg/day for 2 to 6 months to at least 14 retinitis pigmentosa patients (page 89, 2nd column, 2nd full paragraph). Thus, while the prior art does not specifically teach the “results” as claimed in claims 13-17 of administration of valproic acid, the claimed limitation does not appear to results in a patentable difference since the same compound is administered to a patient suffering from a retinal disorder. Applicants are reminded that the Office does not have the facilities and resources to determine that such a result will not occur. Burden is on Applicants to rebut such information. See MPEP 2112.01.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 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.
Claim(s) 9, 11, 18 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsumi et al. (Invest Ophthalmol Vis Sci. 2016; 57(14): 6461-6473), as applied above to claims 1-4, 10, 13-17 and 19, in view of Casero et al. (US20140011857A1, 2014-01-09).
Tsutsumi et al. teach potential neuroprotective effects of an LSD1 inhibitor in Retinal Ganglion cells via p38 MAPK activity (title). Specifically, Tsutsumi et al. teach that tranylcypromine significantly suppressed neuronal cell death following glutamate neurotoxicity and oxidative stress, wherein the intravitreal administration of tranylcypromine significantly saved RGC numbers in an in vivo glaucoma model in mice employing NMDA-induced excitotoxicity (Results). Moreover, Tsutsumi et al. teach that ocular topical administration including intravitreal injection of tranylcypromine may help minimize the risk of systemic adverse events seen in the past clinical use (page 6471, 1st column, 1st full paragraph).
Tsutsumi et al. differ from the instantly claimed invention in that it does not specifically teach that tranylcypromine is administered for at least 14 days, formulated with pharmaceutically acceptable excipients, the retinal disorder is age-related microdegeneration or that the subject is a human.
Casero et al. teach a method of treating a disease or disorder associated with lysin=specific demethylase 1 (LSD1) in a subject, the method comprising the step of administering a compound of formula I, II or III (paragraph 0071). With regards to the disease or disorder, the PG Pub teaches that diseases or disorders include, but are not limited to, retinoblastoma, exudative age-related macular degeneration, diabetic retinopathy and glaucoma (paragraphs 0128 and 0248). Moreover, the PG Pub teaches that the LSD1 inhibitors can be formulated as a pharmaceutical composition comprising the LSD1 inhibitor and a carrier or excipient, wherein the total daily dosage of the compounds will be decided by the attending physician and depend on a variety of factors such as time of administration and duration of administration (paragraph 0066 and 0255). Lastly, the PGPUB teaches that the subject is a human.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Tsutsumi et al. to treat humans and/or age related macular degeneration in view of the teachings of Casero et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Casero et al. teach the use of LSD1 inhibitors in humans as well as the use of LSD1 inhibitors for treating age related macular degeneration.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to formulate tranylcypromine as taught by Tsutsumi et al. with a pharmaceutically acceptable carrier or excipient. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Casero et al. teach LSD1 inhibitors can be formulated with pharmaceutically acceptable carriers or excipients.
Lastly, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to optimize the amount of time the administration of tranylcypromine occurs. One of ordinary skill in the art would have been motivated to make such an optimization, with a reasonable expectation of success, because:
-Casero et al. teach the LSD1 inhibitors can be formulated as a pharmaceutical composition comprising the LSD1 inhibitor and a carrier or excipient, wherein the total daily dosage of the compounds will be decided by the attending physician and depend on a variety of factors such as time of administration and duration of administration.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsumi et al. (Invest Ophthalmol Vis Sci. 2016; 57(14): 6461-6473), as applied above to claims 1-4, 10, 13-17 and 19, in view of Chakrabarti et al. (WO2022/006667A1, 2022-01-013).
Tsutsumi et al. teach potential neuroprotective effects of an LSD1 inhibitor in Retinal Ganglion cells via p38 MAPK activity (title). Specifically, Tsutsumi et al. teach that tranylcypromine significantly suppressed neuronal cell death following glutamate neurotoxicity and oxidative stress, wherein the intravitreal administration of tranylcypromine significantly saved RGC numbers in an in vivo glaucoma model in mice employing NMDA-induced excitotoxicity (Results). Moreover, Tsutsumi et al. teach that ocular topical administration including intravitreal injection of tranylcypromine may help minimize the risk of systemic adverse events seen in the past clinical use (page 6471, 1st column, 1st full paragraph).
Tsutsumi et al. differ from the instantly claimed invention in that it does not specifically teach that tranylcypromine is administered in combination with an anti-inflammatory agent.
Chakrabarti et al. teach a method of treating a condition, the method comprising administering to a subject in need thereof a therapeutically effective amount of at least one agent that inhibits at least one biological activity of the long non-coding RNA HOTAIR, wherein the condition includes, but is not limited, diabetic retinopathy, neovascular glaucoma, ischemic retinopathy, retinopathy secondary to retinal vein occlusion, and age-related macular degeneration, wherein the patient is a human (claims 11 and 20 of the WO). With regards to the agent, Chakrabarti et al. teach that the agent is a histone methylation inhibitor such as DZNep (claims 22 and 24 of the WO). Moreover, Chakrabarti et al. teach that the agent is administered in combination with another therapeutic agent such as an anti-VEGF agent (claim 41 of the WO). With regards to the administration, Chakrabarti et al. teach that the routes of administration of the agents include, but are not limited to, intravitreal administration, wherein administration occurs for an extended period to time including at least 2 weeks (page 69, lines 10-12 and 19-22). Lastly, Chakrabarti et al. pharmaceutical composition comprising the agents and a pharmaceutically acceptable carrier/excipients such as water and sodium chloride (page 67, lines 7-21).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to combine tranylcypromine as taught by Tsutsumi et al. with DZNep for the treatment of glaucoma in view of the teachings of Chakrabarti et al.. One of ordinary skill in the art would have been motivated to make such a combination , with a reasonable expectation of success, because:
-Each agent has been taught individually for treating glaucoma.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
Conclusion
Therefore, No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626