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
This action is written in response to applicant’s correspondence received May 08, 2026. Claims 1-2, 5, 8-9, 13-14, 18-19, 22, 25-26, and 30-31 were amended in the claim set filed May 08, 2026. Claims 83-88 are newly added. Claims 36-37, 39, 41, and 43-44 are cancelled. Accordingly, claims 1-2, 5, 8-9, 13-14, 18-19, 22, 25-26, 30-31, and 83-88 are currently pending and under consideration.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Withdrawn Claim Rejections - 35 USC § 112 - Enablement
Applicant’s amendment of claim 1 to incorporate limitations of previous claims 5 and 8 to recite “a method of decreasing degeneration of retinal ganglion cells in a subject, comprising administering…a calcium-calmodulin dependent kinase (CaMK)…comprises a CaMKIIα…T286D or a CaMKIIβ…T287D” has been fully considered. The specification provides working examples of recited method satisfying the enablement requirement. Thus, the rejection under 35 U.S.C. 112(a) for failing to comply with enablement requirement for claims 1, 2, 9, 13, and 14 is withdrawn.
Priority
The instant application claims priority based on a US Provisional Application No. 63/154,432 filed on February 26, 2021. The provisional application describes claims 1, 13, 83, ([0007]), claims 2, 5, and 8 ([006]), claim 14 ([0009], claims 18, 84 ([0010], [0011], [0013]), claim 19, 22, and 25 [0010]), claim 30 ([0011]), claim 31 ([0013]), claims 36, 39, and 41 ([0014]), claims 43 and 44 ([0015]), claims 85 and 86 ([006], [007]), and claims 87 and 88 ([0011], [0012]). Accordingly, the effective filling dates of instant claims 1, 2, 5, 8, 13, 14, 18, 19, 22, 25, 30, 31, and 83-88 is February 26, 2021.
Support for the recitation of “and the polynucleotide further comprises a gamma-Synuclein promoter” is described in [0008], [0012], and [0014]. However, support for the recitation “and the polynucleotide further comprises a gamma-Synuclein promoter, a Synapsin 1 promoter, a Neurofilament Heavy promoter, or a Thy-1 cell surface antigen promoter” as recited in instant claims 9 and 26 could not be found in US Provisional Application No. 63/154,432. Therefore, instant claims 9 and 26 are not afforded the effective filling date of February 26, 2021.
The instant application also claims priority based on a US Provisional Application No. 63/177,230 filed on April 20, 2021. The provisional application provides support for the recitation “and the polynucleotide further comprises a gamma-Synuclein promoter, a Synapsin 1 promoter, a Neurofilament Heavy promoter, or a Thy-1 cell surface antigen promoter” as recited in instant claims 9 ([0008]) and 26 ([0012]). Accordingly, the effective filling date of instant claims 9 and 26 is April 20, 2021.
Specification
The disclosure is objected to because of the following informalities: The specification teaches “FIGs. 55A and 5F” ([0141]) which contains a typo error because there is no FIG. 55A.
Appropriate correction is required.
Claim Objections
Claims 9, 14, 18, 19, 26, and 31 are objected to because of the following informalities:
Claims 14, 18, and 31 recite “retinal ganglion call axons” which contains spelling errors; therefore, it should read as “retinal ganglion cell axons”.
Claim 9 recites “comprising administering to the subject a a polynucleotide”, and the article “a” is repeated.
Claim 19 recites “administering a viral vector to the subject wherein”, but a comma is missing proceeding the wherein clause, i.e., between the word “subject” and “wherein”.
Claim 26 recites “the method of any claim 18”, which contains a typo. It is recommended to remove the word “any”.
Claim 31, lines 3 to 7 are already recited in claim 18 from which it depends. Thus, the recitation in lines 3 to 7 is redundant and it is recommended to remove this recitation for concise language in the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Enablement
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 18, 19, 22, 25, 26, 30, 31, 84, 87-88 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 a method of treating vision loss caused by degeneration of retinal ganglion cells in a subject, does not reasonably provide enablement for a method of treating vision loss caused by any disease in a subject, not limited to vision loss caused by degeneration of retinal ganglion cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant factors are indicated below:
Nature of the Invention
Claims are directed to a method of treating vision loss in a subject, who has or is at risk for having one or more glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, by administering a calcium-calmodulin dependent kinase (CaMK) isoform, i.e., CaMKIIα comprising a T286D substitution or CaMKIIβ comprising a T287D substitution, or a polynucleotide encoding the CaMK isoform.
Breadth of the Claims (1)
With respect to claim breadth, the standard under 35 U.S.C. § 112(a) entails determining what the claims recite and what claims mean as a whole. Claim 18 merely recites treating vision loss in a subject, which under the broadest reasonable interpretation, is interpreted as treating vision loss caused by any disease with merely increasing expression of recited CaMK isoforms. Claim 18 is not limited to treating vision caused by retinal ganglion cell (RGC) degeneration, rather, claim 18 is drawn to a method of treating vision loss caused by any pathological activity. Further, claim 18 recites “wherein the subject has or is at risk for having one or more glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury”, but this limitation is directed to the subject, not to the cause of vision loss. Therefore, the breadth of the claims encompasses treating vision loss a subject that has or is at risk for having one or more glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, by administering a CaMK.
Guidance of the Specification (1)
The specification discloses working examples demonstrating treatment of CaMKIIa T286D maintains RGC function ([0168], FIGs. 13C and 13D). Although this guidance may reasonably support treating vision loss involving or caused by RGC degeneration, is does not reasonably support the breath of the claims for treating vision loss involving other mechanisms, including cataract, corneal disease, refractive disorders, retinal detachment, age-related macular degeneration, and many other causes of vision impairment. The specification does not provide any guidance or evidence demonstrating that increased expression of CaMKIIα T286D or CaMKIIβ T287D is broadly applicable to the diverse ways of vision loss, including those that do not involve RGCs degeneration or CaMK-mediated signaling.
State of the Art (1)
At the time of filling, the state of the art established that aging is expected to increase vision impairment globally. Steinmetz et al (Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study; The Lancet Global Health; 2020, 9:e144-e160) teach that leading causes of blindness are cataract, followed by glaucoma, related macular degeneration, and diabetic retinopathy (pg. e149, col. 1, para. 3). Stenmetz et al further teach that vision impairment prevalence is consistently high for all these causes (pg. e149, col. 2, para. 3; Fig. 1). Accordingly, a large population of elderly subjects satisfy the “has or is at risk for glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury” limitation simply due to age.
Further, Liu et al (Cataracts; the Lancet, 2017, 390:600-612) teach cataracts is caused by lens nuclear sclerosis and opacity as a result of oxidative stress, insolubilisation, and crosslinking (pg. 600, paragraph bridging col. 1 and col. 2). Liu et al further teach cataractogenesis can be induced by long-term usage of corticosteroids and medications including phenothiazines, busulfan, miotics (pg. 600, col. 2, para. 2). Liu et al also teach other causes of cataract include mechanical trauma, chemical insury, ultraviolet radiation. The teachings of Liu et al demonstrated that diseases causing vision loss operate through distinct mechanisms, not limited to degeneration of RGCs.
Thus, given this diversity and complexity of pathological context of ocular diseases that contribute to vision loss, it would have been highly unpredictable that merely increasing activity of a CaMKII would treat and/or prevent vision loss, and one cannot use the claimed invention without substantial and unpredictable experimentation.
Experimentation Required (1)
In order to practice the claimed invention, an immense amount of experimentation would be required. For example, it would be necessary for one of ordinary skill in the art to screen numerous causes of vision loss (e.g., cataract) and determine which, if any, are treatable by increased activity of CaMKIIα comprising a T286D substitution or CaMKIIβ comprising a T287D substitution.
Breadth of the Claims (2)
The breadth of the claims regarding a method of treating vision in a subject is discussed above under Wands Factor “Breadth of the Claims (1)”. Further, claim 18 recites “the treating vision loss comprises preventing vision loss”. Thus, the claims explicitly encompass preventing vision loss in a subject by administering a CaMKIIα comprising a T286D substitution or CaMKIIβ comprising a T287D substitution.
Guidance of the Specification (2)
The specification does not provide any working example demonstrating prevention of vision loss in a subject. In all examples testing the effect of CaMKII reactivation on RGCs functions, the mice are injured or had vision impairment before administration of CaMKIIα comprising a T286D substitution ([0167])-[0174]) and FIGs. 13A-13Q).
State of the Art (2)
A search of the prior art did not identify any methods which utilized a CaMKIIα comprising a T286D substitution or CaMKIIβ comprising a T287D substitution, which could effectively prevent vision loss in a subject. In fact, no prior art was identified which taught effective prevention of vision loss using any agent similar to the agents utilized in the instant claims.
Experimentation Required (2)
In order to practice the claimed invention, an immense amount of experimentation would be required. For example, it would be necessary for one of ordinary skill in the art to conduct de novo experimentation without a guarantee of success, and further consideration that any positive results (i.e., successful prevention of vision loss in a subject) would amount to a significant advancement in the state of the art.
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an unreasonable amount experimentation would be required to use the invention as claimed. Therefore, claims 18, 19, 22, 25, 26, 30, 31, 84, 87-88 are not considered to be fully enabled by the instant disclosure.
Response to the Arguments
In Applicant’s remarks received on February 05, 2026, Applicant argues that “the application demonstrates that such treatment treats vision loss in a subject wherein the vision loss is due to loss of retinal ganglion cells…CaMKII reactivation preserves visual function” (pg. 7, para. 3) (emphasis added). This argument has been fully considered but it is not persuasive because although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As stated in instant Office Action, under 112(a) rejection for failing to comply with enablement, the breadth of the claims broadly encompasses treating vision loss caused by any mechanism, not limited to degeneration of RGCs. Thus, although the guidance from the specification reasonably support a method of treating vision impairment due to loss of RGCs, it does not reasonably support a method of vision loss or a method of vision loss that comprises preventing vision loss. Therefore, the rejection under 35 U.S.C. 112(a) for claims 18, 19, 22, 25, 26, 30, 31, and newly added claims 84, 87, and 88 is maintained.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: Claims 1, 2, 5, 8-9, 13-14, 83, and 85-86 are directed to a method of decreasing degeneration of retinal ganglion cells (RGCs) in a subject, comprising administering to the subject a calcium-calmodulin dependent kinase (CaMK) or a polynucleotide encoding a CaMK, wherein the CaMK comprises a CaMKIIα T286D variant or a CaMKIIβ T287D variant.
The specification provides working examples with CaMKIIα wild-type, CaMKIIβ wild-type, CaMKIIα T286D variant and CaMKIIβ T287D variant ([0103]). The specification further teaches enhancing the activity of CaMKII variants indeed decreased degeneration of RGCs from excitotoxic or axonal injuries (FIGs. 3A-3T and FIG. 5F; [0140]-[0142]). In fact, the two CaMKIIα T286D and CaMKIIβ T287D variants were most effective in countering excitotoxic or axonal injuries, even at 12 months after injury (FIGs. 6F-6K, and FIG. 6O; [0149]).
As previously stated in Office Action mailed on 02/10/2026, the prior art teaches changes in CaMKII autophosphorylation was observed after retinal stress and CaMKIIα was primarily interrogated using small molecule or peptide inhibitor. For instance, Fan et al (Retinal ganglion cell death and neuroprotection: Involvement of the CaMKIIα gene; Molecular Brain Research, 2005, 139:306-316) teaches caspase-3 activation plays a central role in apoptosis as activated caspases kill cells by degrading structural elements and DNA repair enzymes and by indirect activation of chromosomal endonucleases (pg. 314, left column, second paragraph), and that “CaMKII is involved in the activation of caspase-3, but not in the transcription or translation of the proenzyme” (pg. 314, right-column, second paragraph). Fan further teaches although glutamate caused an increase in phosphorylation at Thr286 of CaMKIIα, the presence of an inhibitory peptide AIP blocked this autophosphorylation significantly and completely inhibited CaMKII-mediated phosphorylation (Fig. 8; pg. 312, left-column, second paragraph). Goebel et al (Selective blockade of CaMKII-α inhibits NMDA-induced caspase-3-dependent cell death but does not arrest PARP-1 activation or loss of plasma membrane selectivity in rat retinal neurons; Brain Research, 2009, 1256: 190-204) further confirmed Fan’s teachings where inhibition of CaMKIIα with AIP in a mouse model of retinal toxicity “fully attenuates caspase-3 activation for at least 8 h following NMDA insult and also significantly improves retinal ganglion cell survival” (Abstract).
Although the closest prior art teaches inhibiting CaMKII using AIP, this neuroprotective strategy for RGCs functions mechanistically different than the instant claimed invention because AIP turns CaMKII off by blocking autophosphorylation of CaMK and prevents its activation toward substrates whereas CaMKIIα T286D and CaMKIIβ T287D variants keep CaMKII on by mimicking the autophosphorylated state which has calcium-independent activity (i.e., autonomous) and allowing activation of substrates.
Conclusion
Claims 1, 2, 5, 8-9, 13-14, 83, and 85-86 are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIWEN SU-TOBON whose telephone number is (571)272-0331. The examiner can normally be reached Monday - Friday, 9:30am - 5:00pm.
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/QIWEN SU-TOBON/
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights