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 .
Restriction/Election
Applicant’s election without traverse of Group 1, claims 1-7, 10, 11 and 19-23 in the reply filed on 01/05/26 is acknowledged.
Claims 8-9, 12-18 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/05/26.
Applicants further elected the species retinal detachment as the injury of group 1, drawn to treating injuries and SYC1127 as the inhibitor. Although applicants also elected the species neurological retinal disease as the neurological disease, SPATA7 as the gene mutation, the group election was drawn to a method of treating an injury. Because the species is drawn to a retinal detachment or retinal neurological disease, claims 19-23 are withdrawn as not reading on the elected species, retinal detachment, because these claims are drawn to hearing loss, spinal cord injury, brain injury or shock, which are not retinal injuries. Claims 1-7, 10 and 11 are under examination.
The species SYC1127 was searched and found to be free of the art, as the compound itself is novel. As such, the search was extended to additional species and art was found which reads on the current claims and the elected species, retinal detachment. An Office action on the merits follows.
Claims Rejections 35 USC 112(A)
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 1-7, 10 and 11 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 treating retinal injuries and retinal cell degeneration with SYC1127, does not reasonably provide enablement for the entire scope of treating all injuries in any tissue with any histone deacetylase inhibitor. 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.
Note that because Applicants have elected the species “retinal detachment,” and group 1, drawn to injury, the enablement rejection will not cover the scope of neural degenerative disease treatments with HATi’s. The enablement analysis for treating injuries with HAT inhibitors follows.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to:
(1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (reversing the PTO's determination that claims directed to methods for detection of hepatitis B surface antigens did not satisfy the enablement requirement). In Wands, the court noted that there was no disagreement as to the facts, but merely a disagreement as to the interpretation of the data and the conclusion to be made from the facts. In re Wands, 858 F.2d at 736-40, 8 USPQ2d at 1403-07. The Court held that the specification was enabling with respect to the claims at issue and found that "there was considerable direction and guidance" in the specification; there was "a high level of skill in the art at the time the application was filed;" and "all of the methods needed to practice the invention were well known." 858 F.2d at 740, 8 USPQ2d at 1406. After considering all the factors related to the enablement issue, the court concluded that "it would not require undue experimentation to obtain antibodies needed to practice the claimed invention." Id., 8 USPQ2d at 1407.
(1) The nature of the invention and (5) The breadth of the claims:
The invention is drawn to a method of treating any injury in any tissue, due to any cause, at any time during the wound healing process, with any histone acetyltransferase inhibitor, which is very broad and unpredictable. HATi’s have different mechanisms of action, which were not well understood at the time of the invention, and their role in wound healing is currently not well understood enough to support a general method of injury treatment.
(2) The state of the prior art:
With regard to the mechanisms of HAT inhibitors, the art recognizes that there are challenges in their development and function because HATs have been shown to function in complexes consisting of many proteins (Wapenaar and Dekker, Clinical Epigenetics (2016) 8:59; abstract). These complexes play a role in the activity and target specificity of HATs, which limits the translation of in vitro to in vivo experiments and causes problems with reactivity, instability, low potency, or lack of selectivity between HAT subtypes and other enzymes, as a characteristic feature of HATs is that they are bi-substrate enzymes that catalyze reactions between two substrates: the cofactor acetyl coenzyme A (Ac-CoA) and a lysine-containing substrate (abstract). This makes the reproducibility potency and the reproducibility of enzyme inhibition experiments difficult, as different studies indicate different catalytic mechanisms for specific HATs, and the use of different HAT enzyme constructs and methods often leads to different proposed catalytic mechanisms (abstract, Table 3, p. 5-6).
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Thus, it was well known in the art that different HAT’s would have different mechanisms, as would their inhibitors, which would produce different effects in vivo.
Regarding wound healing, the art recognizes that it is a dynamic process that requires temporally coordinated inflammatory, proliferative, and remodeling phases, and that the inflammatory response exhibits a double-edged role: a moderate response is essential for normal healing, but excessive or persistent response impedes repair processes (Xiao et al. Current Opinion in Immunology. 2025, 96:102635; abstract). This reference teaches that different histone modifications take place at different phases of wound healing, and that they differ between acute and chronic, as well as the cause, such as a diabetic wound, venous ulcer, pressure ulcer and mechanical stress (p. 5-6; Table 1). Thus, the art recognizes the variant role of histone modifications in wound healing, as well as their variant mechanisms of action.
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(4) The predictability or unpredictability of the art:
Combining the lack of clarity in the art regarding histone acetylation mechanisms, their inhibition, and their varying role throughout the wound healing process in different types of wounds, the art is highly unpredictable. Applicant has not shown enough data to overcome this unpredictability in treating wounds effectively.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
Applicant’s specification only provides one example, which is treating a retinal wound with SYC1127. Although this serves as a model, there is no overall guidance as to how other HAT inhibitors would treat wounds in other tissues, what mechanisms play a role in different types of wounds at different times, or which types of wounds would even benefit form HAT inhibition.
As described supra, the state of the art recognizes that HAT inhibitors are highly variant and that wound healing has different types of histone modifications at different stages and for different types of wounds. This leaves a significant gap in guidance between the one example provided and the many different types of injuries and HAT inhibitors claimed.
(8) The quantity of experimentation necessary:
Because it is uncertain to predict the types of histone modifications in different wounds at different stages, as well as their mechanisms of action, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to determine how to use HAT inhibitors for injury treatment in general with a reasonable expectation of success.
Claim Rejections 35 USC 103(A)
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.
Claim(s) 1-7, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kadiyala et al. (The Journal of Biological Chemistry, 287, No. 31, pp. 25869–25880, July 27, 2012) in view of Stewart et al. (Indian J Ophthalmol. 2018 Dec; 66(12):1751–1762).
Kadiyala teaches that histone acetylation and inflammatory protein expression have been implicated in the pathogenesis of diabetic retinopathy (abstract). This reference further teaches that in diabetically induced rats, minocycline was administered to some of the diabetically induced rats at a dose of 10 mg/kg via intraperitoneal injection, 5 per week, and that acetylated histone H2A, H2B, H3, and H4 were increased approximately 2-fold in the retinas of diabetic rats compared with those of the nondiabetic rats (p. 25870, Col. 1). Kadiyala further teaches that in cultured retinal Müller glia, grown in a diabetes-like concentration of glucose in vitro, acetylation and induction of inflammatory proteins were significantly inhibited by the histone acetyltransferase inhibitor, garcinol, and its antisense nucleotide, against the histone acetylase, p300 (abstract). This reference teaches that in the transformed retinal Müller cells, garcinol significantly inhibited histone H3 acetylation, suggesting that the administration of garcinol, or other HATi’s will treat retinal damage induced by diabetes (p. 25873, Col. 2). This reference concludes that hyperglycemia causes acetylation of retinal histones and the upregulation of inflammatory proteins, and that HATi’s are a potential pharmacological intervention and therapeutic target for preventing or treating diabetic retinopathy (p. 25878, Col. 2).
The difference between the prior art and the instant claims is that the prior art does not teach a method of reducing to practice administering garcinol directly to a subject with retinopathy, or explicitly state that diabetic retinopathy is a retinal injury.
Stewart teaches that twenty-five percent of diabetes-related vision loss stems from complications of proliferative diabetic retinopathy and that intravitreal injections of drugs that inhibit the actions of vascular endothelial growth factor have been the standard in vivo treatment (abstract). Stewart also teaches that for subjects having proliferative diabetic retinopathy, advanced pathologies, such as traction retinal detachments (TRDs), combined traction/rhegmatogenous retinal detachments (TRD/RRDs), vitreous hemorrhages, rubeosis iridis, and traction maculopathies commonly cause loss of vision, but surgically treated and would benefit from pre and post-surgical treatments to control inflammation at the injury site (abstract; p. 1754, Col. 2).
It would have been obvious to one of ordinary skill in the art at the effective filing date of the invention to have administered the garcinol of Kadiyala to a subject that has diabetically induced retinal detachment because Kadiyala teaches that garcinol is effective in reducing the upregulation of inflammatory proteins in diabetic retinopathy via HAT inhibition. One would be motivated to do so because Kadiyala teaches that garcinol significantly inhibits hyperglycemia and its corresponding inflammation that causes proliferative retinopathy, and Stewart teaches that this condition often comes with subsequent retinal injuries, which are in need of inflammatory regulation in the retina. As such, there is a reasonable expectation of success that administering garcinol can effectively treat a subject having diabetic retinal detachment by reducing histone acylation and inflammation.
This meets the limitations of claim 1 because Kadiyala teaches treating diabetic retinopathy with the HATi, garcinol, and Steward provides motivation to do so for subjects with diabetically induced retinal injuries. Claim 2 is met because the histone acetyltransferase inhibited is p300. Claim 3 is met because Kadiyala teaches that garcinol intrinsically binds the active site of p300, or the promoter, to regulate expression (p. 25869, Col. 2, para. 2). Claim 4 is met because Kadiyala also teaches that the antisense against p300 intrinsically binds the entire protein, which is not simply binding the active site (p. 25874, Col. 2, para. 2). Claim 6 is met because Kadiyala teaches garcinol. Claims 7 and 11 are met because this combination renders obvious treating diabetic retinal injury and retinal detachment. As to claims 5 and 10, these are rendered obvious because the administration of garcinol would inherently have the same effect of administering garcinol. Kadiyala teaches that garcinol was administered to Müller cells, and to control inflammation, which would allow for healing and regeneration. Furthermore, claims 5 and 10, as well as the inherent mechanisms described in claims 2-4 do not patentably distinguish the claimed invention from the prior art. The MPEP states: [T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id.
Here, the same composition is being administered to the same types of cells, even though it is not done in vivo. The mechanism by which it works is inherent to the method itself, absent evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654