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
This office action is in reply to Response to Election/Restriction filed 14 May 2026 for application 18/602,668 filed on 12 March 2024. Currently, claims 1-8 are pending.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 14 May 2026 is acknowledged.
Applicant’s election of compound 2, illustrated below, in the reply filed on 14 May 2026, is acknowledged:
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The elected species, per the Applicant’s Remarks, reads upon claims 1-5. As such, claims 6-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. Election was made in the reply filed on 14 May 2026.
The election was searched and found to be free of the prior art.
Claims 1-5 are allowable. Claims 6-8, previously withdrawn from consideration as a result of a restriction requirement, requires all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between Groups, as set forth in the Office action mailed on 08 April 2026, is hereby withdrawn and claims 6-8 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Specification
The disclosure is objected to because of the following informalities: image in para. 0027, 0048, 0077 (table 1), 0097, 00102, 00109, 00113, 00117, 00121, 00125, 00129, 00133, 00137, 00141, 00145, 00149, 00153, 00157, 00161, 00165, 00169, 00173, 00177, 00181, 00185, 00189, 00193, 00197, 00201, 00205, 00209, 00213, 00217, 00221, 00225, 00229, 00233, 00237, 00241, 00245, 00249, 00253, 00257, 00261, 00265, 00269, 00273, 00277, 00281, 00285, 00289, 00293, 00297, 00301, 00305, 00309, 00313, 00317, 00321, 00325, 00329, 00333, 00337, 00341, 00345, 00349, 00353, 00357, 00361, 00365, 00369, 00373, 00377, 00381, 00385, 00389, 00393, 00397, 00401, 00405, 00409, 00413, 00417, 00421, 00425, 00429, and 00433 are not well-resolved.
Appropriate correction is required.
Claim Objections
Claims 4 and 5 are objected to because of the following informalities: structure drawings are not well resolved (i.e. too blurry). Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claims 6-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A review of the rejected claim language indicates that these claims are drawn toward “a method for preventing or treating an ophthalmic disease, the method comprising administering to a subject in need thereof the compound of claim 1…” in the case of claim 6, and “the method of claim 6, wherein the ophthalmic disease is endophthalmitis, keratitis, conjunctivitis, keratoconjunctivitis, uveitis, blepharitis, scleritis, iritis, glaucoma, retinal degeneration, retinitis pigmentosa, retinal detachment, retinal pigment epithelium detachment, retinal break, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, ischemic proliferative retinopathy, cone dystrophy, proliferative vitreoretinopathy, retinal artery occlusion, retinal vein occlusion, Leber’s optic atrophy, corneal neovascularization, retina choroidal neovascularization, wet and dry macular degeneration, or age-related macular degeneration” in the case of claim 7. A description of the term “a method of treating or preventing a disease or disorder…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ Application/Control Number: 18/335,687 369, 372-73 (Fed. Cir. 1984).
In Applicant’s originally filed specification, Bromodomain Extra-Terminal family proteins including BRD2, BRD3, BRD4, and BRDT are taught to be widely expressed in various tissues and associated with various diseases including cancer, metabolic diseases, and inflammation. The Applicant also provides working examples of biochemical binding to BRD2 and BRD3 and treating induced retinal and macular degeneration in mouse models. The Examiner notes that the term “subject” is not defined in Applicant’s specification. Therefore, subject is broadly construed to refer to any animal with eyes. They do not demonstrate that the product is capable of the recited limitations to the breadth and scope of which the broadest reasonable interpretation requires. D. Dubielzig (Comparative anatomy of the vertebrate eye and evolution, University of Wisconsin-Madison School of Veterinary Medicine 2014) who illustrates broad differences in ocular anatomy in several different species such as hagfish (slide 4), shark (slide 9), higher teleosts (slide 16), frogs and turtles (slide 23), diving birds (slide 48), etc. Zhang et al. (Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma, Nature Reviews Drug Discovery 2012, 11, 541-560) describes some of the benefits and challenges of treating ocular diseases. The accessibility of the eye facilities treatment through methods such as eye drops or injections. In contrast, ocular barriers such as blood-ocular barriers, blood flow, lympathic clearance, and tear dilution impede drug transport and lower drug efficacy. Zhang also notes that various drugs have been developed that inhibit complement activation and angiogenic pathways, but that the therapeutic need has not yet been met, despite these advances (pg. 541). Zhang teaches several categories of drugs including anti-VEGF therapy for anti-angiogenic therapy for the treatment of neovascular ocular diseases and intraocular pressure-lowering therapies for the treatment of glaucoma (pg. 543), demonstrating that no therapy is ubiquitously relevant. The idiopathic factors, etiology, patient populations, co-morbidities, etc. undermine the concept that the working examples provided in the instant specification are prophetic to the final therapeutic application of the invention to all the various diseases claimed. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structures, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predicable which are known to one of ordinary skill in the art, more evidence is required to show possession. One of skill in the art would not recognize from the disclosure that the applicant was in possession of a “method of treatment” for the diseases as claimed.
Claims 6-7 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 inhibition of BRD2 and BRD3 protein activity, exhibiting inhibition of induced retinal degenerative effects in mice, and exhibiting enhanced recovery from induced macular degeneration, does not reasonably provide enablement for the broad genus of ophthalmic diseases and species such as endophthalmitis, keratitis, conjunctivitis, keratoconjunctivitis, uveitis, blepharitis, scleritis, iritis, retinal detachment, retinal break, cone dystrophy, proliferative vitreoretinopathy, and Leber’s optic atrophy. 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.
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: (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. See MPEP § 2164.01(a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant. A discussion of these factors as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) Nature of invention –
The applicant’s claims are broad. Claim 6 is directed to “a method for preventing or treating an ophthalmic disease, the method comprising administering to a subject in need thereof the compound of claim 1…”. The term subject is very broad, encompassing not just humans with disparate etiologies, patient populations, and numerous other relevant factors, but also includes any creature of whom this treatment may be relevant for, including mammals and non-mammals. “Subject” is not defined in Applicant’s specification, and, thus, is not limited to humans or mammals. While it is recognized that there are broad similarities between mice and humans in ocular tissue, this is not true for other types of animals such as lizards or birds as illustrated by Dubielzig who illustrates broad differences in ocular anatomy in several different species such as hagfish (slide 4), shark (slide 9), higher teleosts (slide 16), frogs and turtles (slide 23), diving birds (slide 48), etc. While bromodomain proteins are highly conserved, there is no demonstrated reasonable expectation for the same therapeutic outcomes for all subjects when defined by the requirements of broadest reasonable interpretation. As the specification discloses working examples only performed in mouse models, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification satisfies the possible breadth of subjects possible.
(C) The state of the prior art –
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05(a). Zhang describes some of the benefits and challenges of treating ocular diseases. The accessibility of the eye facilities treatment through methods such as eye drops or injections. In contrast, ocular barriers such as blood-ocular barriers, blood flow, lympathic clearance, and tear dilution impede drug transport and lower drug efficacy. Zhang also notes that various drugs have been developed that inhibit complement activation and angiogenic pathways, but that the therapeutic need has not yet been met, despite these advances (pg. 541). Zhang teaches several categories of drugs including anti-VEGF therapy for anti-angiogenic therapy for the treatment of neovascular ocular diseases and intraocular pressure-lowering therapies for the treatment of glaucoma (pg. 543), demonstrating that no therapy is ubiquitously relevant. Therefore, it is reasonable to conclude that the current state of the art is unpredictable, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for the treatment of the diseases claimed.
(D) The level of one of ordinary skill in the art –
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
These hurdles render application of “a method of treatment” of the diseases and conditions claimed to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E) Existence of working examples & (F) Amount of direction or guidance by the inventor –
As previously established by Zhang, ophthalmic diseases are complex diseases. Conversely, the specification does not demonstrate a means to treat these diseases in subjects of need to the requirements of broadest reasonable interpretation. Instead, the instant specification on provides biochemical and in vivo results that reasonably enables treating diseases under the species of macular degeneration, glaucoma, and those related to angiogenesis. The Applicant references and speculates on results from Zhao et al. (pg. 9, line 12) about the protective neuroinflammatory effects of BET protein inhibitors, but does not demonstrate this with working examples. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims.
(G) Quantity of experimentation needed to make or use the invention –
Taken together, the prior art demonstrates that the diseases arise from multiple factors and etiologies. This cover a breadth and scope of material that is inadequately addressed in the instant specification. While the specification demonstrates biochemical binding and reduction in retinal degeneration in mouse models, it does not demonstrate efficacy in other claimed diseases, and how the claimed compounds will be able to matriculate into a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claimed invention and the unpredictability in successful application as described by claims 6-7, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in treating the diseases and conditions claimed. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of ordinary skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
Claims 1-5 and 8 are allowable.
Reasons For Allowance
The following is an examiner’s statement of reasons for allowance: the elected species compound 2 was not found in the prior art in a 100% embodiment. Furthermore, chemical formula I was not found in the prior art in a 100% embodiment. The closest match includes naphthalene-carboxamide derivatives such as CAS 3110552-40-1, illustrated below, which lacks the benzyl carboxamide moiety of chemical formula I:
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As such, all species included in claims 4-5 and chemical formula I are therefore neither anticipated nor made obvious by the prior art and are therefore novel.
The species of claim 8, diabetic retinopathy, glaucoma, uveitis, wet and dry macular degeneration or age-related macular degeneration, appear to be supported by the instant specification, specifically by working examples 2 and 3. Bennis et al. (Comparison of mouse and human retinal pigment epithelium gene expression profiles: potential implications for age-related macular degeneration, PLoS ONE 2015, 10, 10, e0141597) teaches that the gene expression and function annotation are very similar between human and mouse retinal pigment epithelium (abstract). Such similarities and differences were explored in several categories including oxidative stress, drusen and complement system, Bruch’s membrane and vascularization, and tight junctions of the outer blood-retina barrier. Conclusively, they determined that there are a number of related gene expressions, biological functions and canonical pathways assigned to the retinal pigment epithelium of both species, while also identifying several points where the species diverge genetically and phenotypically (pg. 14 – conclusion). As such, unlike many other tissues or organ systems, due to the highly conserved nature between mouse and human ophthalmic organs, the Applicant’s specification gives a preponderance of evidence of being enabling for treating ocular inflammation and degeneration.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Summary
Claims 6-7 are rejected under 35 U.S.C. 112(a). Claims 1-5 and 8 are allowable.
Conclusion
Claims 6-7 are rejected. Claims 1-5 and 8 are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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