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 .
Priority
The present application U.S. Apply. Ser. No.:17/605,489, Filed October 21, 2021 is a 371 Nat’s Stage entry of WO Apply. 2020/219634A1 (i.e., PCT/US2020/029455), Intern.’ l Filing Date: April 23, 2020, Intern.’ l Pub. Date: October 29, 2020, which claims priority from U.S. Prov. Apply. No. 62/837,741, Filed: April 24, 2019
Status
This Request for Continued Examination (R.C.E.) is in response to March 18, 2026 Applicants’ Amendment and Request for Reconsideration After Non-Final Amendment.
Status of the Claims:
Claims 1, 3-6, 8-9, 11, 18-19, 22-25, 27-28 and 30 are pending and are under examination;
Claims 1, 3, 5, 19, 22 and 24 are newly amended; and
Claims 2, 7, 10, 12-18, 20-21, 26, 29, 31-36 are cancelled
In the above-identified application.
In this RCE, for organizational purposes like rejections are grouped by type (i.e., both previously presented and new, respectively, status and/or appropriate responses are addressed accordingly) in identified sections below.
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on March 18, 2026 is in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
CLAIM REJECTIONS - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims
particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
[1] PREVIOUSLY PRESENTED REJECTIONS UNDER - 35 USC § 112(B) & (A) WITHDRAWN
[a] Rejection of claims 1, 4, 9, 11, 12, 16 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para., are WITHDRAWN for being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention due to claim amendments and corresponding arguments.
Discussion Applicants’ Arguments and Examiner Response/Comments re. [a]
While Applicants disagreed with the original rejections set forth in this section, Applicants arguments here were found persuasive in combination with claim amendments (i.e., esp. independent method claims 1 and 19 and corresponding, addressed outstanding substantive rejections) to:
recite compounds of Formula (I) or pharmaceutically acceptable salts thereof; and
define that reverse amyloid b toxicity improve function of one or more specific cell types one or more cell types selected from neuronal, non-neuronal, or neuro-sensory cells, due to reducing deposited amyloid b, improve function of reduce or reverse the course of an amyloid associated diseases or disorder (i.e., which comprises administration of a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof); and
provide evidence to support enablement of amended claims.
[b] Rejection of claims 1, 3-6, 8-9, 11-12, 16, 19, 22-25, 27- 28, 30-31 and 34 under 35 U.S.C. § 112(a), 2nd para, for lack of enablement WITHDRAWN per claim amendments; i.e.,
where claim amendments include, but is not limited to:
amendments to Independent claims 1 and 19 to now recite compounds of Formula I and acceptable salts thereof;
deletion of the terms “hydrate solvate or polymorph thereof) and arguments; and
corresponding biological arguments and support explaining effects of claimed compounds on neurotoxic levels and the like.
Based on the foregoing, any outstanding arguments and the rejections under this section have been rendered moot and resulted in withdrawal of 35 USC § 112 [a] & [b]rejections identified supra.
[2] NEW 35 USC § 112(B) REJECTIONS
Claims 8-9 and 27-28, respectively, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In general, claims of the invention recite indefinite, vague, ambiguous or unclear defined functional terms and/or language (i.e., such that exact scope cannot be ascertained).
Claim 8, 9, 27 and 28 recite examples of a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) , which may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claims 8 and 27 and 9 and 28, resp. recite broad and narrow limitations set forth below:
Claim(s) #
broad recitation (in bold here)
and
narrower statement of range/limitation (appear in parentheses & in bold text below)
8 and 27
early and intermediate dry (non-exudative) age-related macular degeneration
exudative ("wet") macular degeneration
early and intermediate dry non-exudative age-related macular degeneration,
exudative "wet" macular degeneration
9 and 28
focal and general retinal light sensitivity in photopic mesopic (light adaptation) conditions
focal and general retinal light sensitivity in photopic mesopic scotopic (dark adaptation) conditions
focal and general retinal light sensitivity in photopic mesopic light adaptation conditions
focal and general retinal light sensitivity in photopic mesopic scotopic dark adaptation conditions
Appropriate correction is required accordingly.
PRIOR ART REJECTIONS
Rejection Under 35 U.S.C. 102
Maintained & Clarified with Supporting Evidence
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.
Claims 1, 3-6, 8-9, 11, 18-19, 22-25, 27-28 and 30 (i.e., previously included claim 31, now cancelled) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parsons et al., “MRZ-99030 – A Novel Modulator Of Aβ Aggregation: I – Mechanism Of Action (Moa) Underlying The Potential Neuroprotective Treatment Of Alzheimer's Disease, Glaucoma And Age-Related Macular Degeneration (AMD)”, Neuropharmacology, Vol. 92, May 2015, Pages 158-169 ; https://doi.org/10.1016/j.neuropharm.2014.12.038 (“Parsons”)
as evidenced by:
Ong et al. “Ocular amyloid imaging at the crossroad of Alzheimer’s disease and age-related macular degeneration: implications for diagnosis and therapy”, Journal of Neurology (2019) 266:1566–1577 (Pub: 28 August 2018; https://doi.org/10.1007/s00415-018-9028-2;
Reiss et al., “Amyloid toxicity in Alzheimer’s disease”, Rev. Neurosis. 2018, pp.1-15, https://doi.org/10.1515/revneuro-2017-0063); and
Rammed et al., (2014), P4-378: REVERSAL OF AB-INDUCED DEFICITS IN LONG-TERM POTENTIATION (LTP) IN VITRO AND IN VIVO BY MRZ-99030. Alzheimer's & Dementia, 10: P926-P926. https://doi.org/10.1016/j.jalz.2014.07.147
The Present and Claimed Invention
In general, amended claims 1 and 19 are directed to methods to reverse amyloid ß toxicity by reducing deposited amyloid ß, and improve or restoring function of one or more cell types selected from neuronal, non-neuronal, or neuro-sensory cells, or a combination thereof, thereby reversing the course of an amyloid associated disease or disorder and improving the disease or disorder symptoms in a subject in need, either by administering:
a compound of Formula (I) or a pharmaceutically acceptable salt thereof (i.e. claim 1); or
a therapeutically effective amount of: amorphous amyloid ß cluster comprised of amyloid ß1-42 and compound of Formula I, or a pharmaceutically acceptable salt thereof (i.e., claim 19)
The instant claims are directed to:
treatment of patients with Alzheimer’s and ophthalmic diseases (inc. glaucoma, macular denergeration etc.) (i.e., see claims 6, 8-9, 11, 25, 27-28 and 30); and
provide NO specific amounts (quantities, dosages, stoichiometric ratios etc.) of a compound of Formula (I) or a pharmaceutically acceptable salt thereof of the present invention to be delivered or administered pharmaceutically acceptable or therapeutically effective amounts (i.e., whether in specific quantities, dosages, excess amounts, stoichiometric ratios or excess, etc.)
The instant specification teaches:
a pharmaceutically acceptable or therapeutically effective amount is administered in para. [0197] to result in desired biological activity (i.e., does not appear result in different results)
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Representative specification examples teach how compounds of Formula (I) or a pharmaceutically acceptable salt thereof may be dosed (i.e., see therein for more details):
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Parsons Reference
Parsons generally discloses and teaches:
[1] methods, therapeutic approaches, that administers a compound of Formula (I) identified as MRZ-99030 and discussed reduced amyloid toxicity and Aβ accumulation a method admin formula (I) to AD patients directed to:β-amyloid (Aβ) is a major endogenous pathogen in Alzheimer's disease (AD) (i.e. which reads on claims 1 and 19); and summarizes that:
Soluble Aβ oligomers are the major cause of synaptoxicity/neurodegeneration in AD.
MRZ-99030 promotes off-pathway, non-toxic oligomerization of A
MRZ-99030 reversed the synaptotoxic effects of Aβ oligomers in vitro and in vivo.
[2] “ . . . effects of MRZ-99030 on Aβ oligomerization under more physiological/ pathophysiological conditions in biological systems. Here we demonstrate that this small dipeptide compound successfully ameliorates deficient hippocampal LTP and rescues in vivo learning and memory function impaired by acute administration of Aβ oligomers (i.e., see Introduction, last para) .
[3] use and formation of b-amyloid clusters or aggregations (i.e., identified therein as MRZ-99030, novel modulator of Aβ aggregation) formed form a combination of β-amyloid1-42 (Aβ1-42) with the dipeptide D-Trp-Aib for treatment of Alzheimer's disease, glaucoma and age-related macular degeneration (I.e., which reads on claim 19, 22-25 and 27-28) and is directed to the same patient population as in the instant claims
Parsons: MRZ-99030
Claimed Invention Formula (I)
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MRZ-99030 encompassed by claimed invention, where R1 = R2 = R4 = R7 = H; R3 = -OH; R5 = R6 = -C1-6-alkyl = CH3
[4] where such aggregate cluster exhibit an in vivo neuroprotective potential after systemic and topical administration in animal models for aforementioned diseases; and
[5] the mechanism of action underlies the potential neuroprotective treatment of the identified neurological or ophthalmic disease that does not directly prevent early protein/protein interactions between monomeric Aβ, but rather promotes the formation of large, non-amyloidogenic, amorphous Aβ aggregates and thereby reduces the amt. of intermediate toxic sol. oligomeric Aβ species. (i.e., which read on elements defined in claims 1,19 and dependent claims):
[6] Moreover, Parsons addresses
“Therapeutic approaches addressing β-amyloid1–42 (Aβ1–42) aggregation represent a promising neuroprotective strategy for the treatment of Alzheimer's disease, dry age-related macular degeneration (AMD) and glaucoma” as in the claimed invention ;
MRZ-99030 is a dipeptide containing d-tryptophan and 2-amino-2-methylpropionic acid in clinical development for the topical treatment of glaucoma and AMD (i.e., see ABSTRACT therein)”, which is directed to the same patient population as that of the claimed invention.
“The affinity of MRZ-99030 to Aβ1–42 determined by SPR was 28.4 nM but the ratio of compound to Aβ is also important: a 10–20 fold excess of MRZ-99030 (THE COMPOUND) over Aβ … required for effective modulation of protein/protein interactions. For example, in glaucoma, assuming a maximal Aβ concentration of 1–15 nM in the retina, up to 150 nM MRZ-99030 could be required at the protein target. In line with this consideration, MRZ-99030 was able to prevent Aβ-induced toxicity on PC12 cells, retinal ganglion cells and retinal pigment epithelium cells when present at a 10–20 fold stoichiometric excess over Aβ (i.e., which reads on claimed invention regardless of whether compound of Formula (I) or pharmaceutically acceptable salt are administered in therapeutically or pharmaceutically effective amounts).”
Ong, Reiss and Rammed References
[7] Ong and Reiss, respectively, teach ALL patients with Alzheimer’s disease, glaucoma and age related macular degeneration exhibit amyloid toxicity; and
Rammed teaches that MRZ-99030 can both prevent and reverse Aβ-induced LTP deficits by modulating aggregation into less toxic forms, offering in vitro and in vivo evidence novel approach to Alzheimer’s therapy (i.e., see Abstract therein).
When considered in its totality, patients with aforementioned diseases have amyloid toxicity that can be reversed to make nexus that amyloid toxicity exists as taught by Parson as evidenced by Ong, Reiss and Rammed, which effectively provides supportive evidence that primary reference Parsons is teaching and that is indicative of inherency.
It is noted that the phrase “reverse amyloid ß toxicity by reducing deposited amyloid ß” is an expected property of the composition. The prior art anticipates performance of the claimed steps (i.e., requiring administration of compounds of the claimed invention alone or as amorphous amyloid ß cluster formed from amyloid ß1-42 and compound of Formula I or a pharm. accept. salt thereof) with the claimed composition (i.e. compounds of the present invention in therapeutically effective or pharmaceutically acceptable amounts as defined) to the claimed patient population (i.e., where patients with Alzheimer’s disease (AD), age-related macular degeneration (AMD), and glaucoma share features linked to amyloid-β (Aβ) deposition and exhibit amyloid toxicity).
Therefore the composition claimed and the composition of the prior art are expected to have the same properties (i.e. “reverse toxicity and improved function”), absent evidence to the contrary.In patent law, a feature is inherent if it is necessarily present in the prior art, even if not explicitly disclosed.
Therefore, Parsons anticipates the claimed invention as evidenced by additional cited references supra.
Response: 3/18/2026 Applicants Arguments: 35 U.S.C.§102(a)(1) as anticipated by Parsons
As set forth supra, the updated rejection under 35 U.S.C. § 102(a)(1), as being anticipated by Parsons evidenced by newly cited references in light of new claim amendments now addresses Applicants March 18, 2026 traversal arguments; i.e., e.g.,
see it appears that the aforementioned references teach that compounds such as MRZ-99030 (i.e., neuroprotective D-Trp-Aib) improve disease or disorder symptoms reverse amyloid ß toxicity and improve function of neuronal, non-neuronal, or neuro-sensory cells as recited in amended claims (i.e., without reliance on van Dyck or any improvements directed to Lecanemab or Aducanumab)’
Therefore, Parsons as evidenced by cited references (i.e., Ong, Reiss and Rammed) anticipates the claimed invention.
Non-Statutory Double Patent Rejections
Outstanding September 24, 2025 Final Rejections & Applicants Response Arguments
[1] Non-Statutory Double Patent Rejections MAINTAINED
Rejection of claims 1, 19 and 22 (i.e., claim 18 cancelled) on the ground of non-statutory obviousness-type double patenting is MAINTAINED as being unpatentable over claims 1-4, 7, 12 and 14 of U.S. Patent No. 11,891,455 B2 to Repasi et al. (371 Date Filed: March 23, 2022; Issued: February 6, 2024).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the treatment methods of the instant invention seen in Claims 1, 18, 19, 22 and 34 overlap in claimed matter with compounds and corresponding pharmaceutical compositions of claims 1-4, 7, 12 and 14 of U.S. Patent No. 11,891,455 B2.
Here, the same compounds of Formulas (I) are recited in both the instant application and the U.S. Patent No. 11,891,455 (i.e., see specification and claims therein).
Although the aforementioned issued patent claims specific chemical compounds and pharmaceutical compositions thereof, the abstract and disclosure of that patent, i.e., e.g.,
recites polymorphic forms of (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid
that read on corresponding compounds of Formula (I) of the instant invention.
In the instant scenario:
the issued U.S. Patent 11,891,455 B2. is directed to the treatment of a disease by administering a compound of Formula (I), while the present application is directed towards patenting the compounds of Formula (I).; and
where the compounds disclosed therein teaches the instant utility as the claimed invention, because U.S. ‘455 Pat. is directed toward unmet medical need, development and uses of such ultrapure compounds “in methods to treat diseases related to Aβ toxicity including Aβ-associated neurodegenerative diseases, for example but not limited to dry AMD, glaucoma, and AD, since dosing with ultrapure compounds may reduce cumulative expose of a subject to toxic impurities present within cumulative doses administered over decades. This is especially true for oral dosing, which, due to higher doses, would lead to a much higher absolute impurity exposure.(i.e., see U.S. ‘455 Pat. generally and esp. col. 2, at lines 24-32, and in embodiments at col. 22, lines 38-67 to col. 23, lines 1-24)
In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a non-statutory double patenting context. See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
However, one skilled in the art would recognize that the issued patent specifically contains the compounds of Formula (I) seen in claim 1 in the instant application.
Based on the above, one of ordinary skill in the art would have an expectation of success in developing methods to reverse amyloid ß toxicity by reducing deposited amyloid ß, improve or restore cell function (i.e., neuronal, non- neuronal, or neuro-sensory cells types, or a combination), thereby reversing or improving amyloid associated disease, disorder or symptoms in a subject in need, which use and adapt polymorphic forms of (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid (i.e., compounds with same chemical core structures possessing desired chemical/ physical activities) that read on Formula (I) or pharm. acceptable salts thereof of U.S. ‘455 Pat,), because the claimed invention is directed to treatment of same diseases and/or utilities, which include diseases AMD, glaucoma, AD, treatment thereof and the like.
One of ordinary skill in the art would have been motivated in adapting polymorphic and/or single isomeric compounds of US ‘455 Pat, ]for methods to reverse amyloid ß toxicity in a subject in need thereof in order to address unmet medical needs to address the same diseases, disorders with the same utility as in the claimed invention.
Based on the foregoing,, the claimed invention is rendered obvious over the U.S. ‘455 Pat. and teachings therein.
Appropriate action is required accordingly.
Applicants comments of record are noted (i.e., March 18, 2026 R.C.E., June 12, 2025 Amendment Remarks, and reiterated in September 24, 2025 Final Office Action) below:
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CONCLUSION
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/G.C.H./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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