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 .
Election/Restrictions
Applicant’s election without traverse of:
Species I: The agent that decreases the expression of LRRK2 by inducing LRRK2 mRNA decay is (b) 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR/ZMP) or 5-aminoimidazole-4-carboxamide riboside (AICAr);
Species II: The additional therapeutic agent is levodopa; and
Species III: The Leucine rich repeat kinase 2 (LRRK2)-associated disorder or condition is a neurodegenerative disease in the reply filed on December 08, 2025 is acknowledged.
The Examiner respectfully notes species I, II and III collectively read on claims 1-3, 6-7, 12-13, 21, 23-27, 29-30 and 35.
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed on 12/08/2025 have been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
The claim set filed November 21, 2023 has been entered. Claims 4-5, 8-11, 14-20, 22, 28, 31-34, and 36-44 are canceled. Thus, claims 1-3, 6-7, 12-13, 21, 23-27, 29-30 and 35 as amended are examined on the merits herein.
Claim Rejections - 35 USC § 102
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, 6-7, 13, 23-24, 26, 29-30 and 35 are rejected under 35 U.S.C. 102((a)(1)) as anticipated by Marangos et al. (Published 16 February 1993, US-5187162-A, PTO-892) as evidenced by Liu et al. (Published 27 June 2023, The EMBO Journal, Vol. 42, Article No. e113410, pp. 1-20, IDS filed 12/08/2023).
Regarding claims 1-3, 6-7, 13, 23-24, 26, 29-30 and 35, Marangos teaches preventing neural tissue damage caused by increasing release of excitatory amino acids (EAA) by increasing extracellular concentrations of adenosine, see Col. 4, lines 65-68.
Marangos teaches the adenosine regulating agents include AICA riboside (e.g. the agent is 5-aminoimidazole-4-carboxamide riboside (AICAr), required in claim 13, line 9; and claim 35, line 9) and its prodrugs, which show the beneficial adenosine regulating / EAA inhibiting properties, but also are both site and event specific, avoiding the unwanted global action of known adenosine agonists, see Col. 5, lines 1-6.
Marangos teaches increasing the extracellular concentration of adenosine in the brain of an individual is drawn to the treatment of Parkinson’s disease in the affected individual (e.g. the subject in need thereof, required claim 1, line 2, and claim 2, line 2) and in related neurodegenerative diseases, where such diseases include Alzheimer’s disease (e.g. the neurodegenerative disease, required in claims 6-7,29, and 30), see Col. 5, lines 7-13.
Marangos teaches adenosinergic agents which selectively increase extracellular adenosine levels in the areas of the brain affected by a neurodegenerative condition, such as Parkinson’s disease are preferred; thus, a preferred aspect is directed to the use of adenosine regulating agents which selectively enhance extracellular adenosine concentration in neural tissue to protect against neurodegenerative damage (e.g. reducing neuronal cell death or neurodegeneration, required claim 2, lines 1-2), See Col. 6, lines 37-45.
Marangos teaches example compounds useful in these methods include AICA riboside and AICA ribotide (e.g. the agent is 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR/ZMP), required in claim 13, line 8; and claim 35, line 8), see Col. 6, lines 45-60.
Marangos teaches the compounds can be taken up by cells (e.g. contacting the cell with the agent and the cell required in claims 23-24 and 26), see Col. 6, line 61.
Marangos teaches utilizing agents which act via an adenosine mechanism (adenosinergic) to inhibit this progressive deterioration in Parkinson’s patients (e.g. preventing neuronal cell death or neurodegeneration, required in claim 2, lines 1-2), Col. 12, lines 35-40.
Marangos teaches it is anticipated that adenosinergic compounds useful in said methods will be effectively administered in amounts ranging from about 0.01 mg/kg/day to about 500 mg/kg/day (e.g. an effective amount of the agent, required in claim 1, line 3 and claim 2, line 3), see Col. 12, lines 60-65.
With respect to limitations:
(a) “that decreases the expression of LRRK2, wherein the agent induces LRRK2 mRNA decay, thereby treating the LRRK2-associated disorder or condition in the subject”, required in claim 1, lines 3-5;
(b) “wherein the neuronal cell death is LRRK2-mediated cell death”, required in claim 3; and
(c) “reducing LRRK2 expression in a cell comprising contacting the cell with an agent that induces LRRK2 mRNA decay, thereby reducing LRRK2 expression in the cell”, required claim 23; are all reasonably interpreted by the Examiner to be functional consequences of administering the agent to the subject having the LRRK2-associated disorder or condition which includes both Parkinson’s disease and Alzheimer’s disease as evidenced by Applicant within claim 7 and claim 30.
Additionally, since Marangos teaches administering an effective amount of AICA riboside as an adenosine regulating agent that is both site and event specific that increases extracellular adenosine levels in the areas of the brain affected by a neurodegenerative condition, preferably Parkinson’s disease; the functional consequence is met by the method taught by Marangos because Marangos teaches administering the required agent to the required patient population in an effective amount to treat or prevent neural damage associated with Parkinson’s disease as discussed above.
Moreover, as evidenced by Liu, Liu discloses upon AICA riboside (AICAr) treatment the RNA binding protein AUF1 is recruited to the AU-rich elements (ARE) of LRRK2 mRNA leading to the recruitment of the decapping enzyme complex DCP1/2 and decay of LRRK2 mRNA. AICAr suppresses LRRK2 expression and rescues LRRK2-induced dopaminergic neurodegeneration and neuroinflammation in Parkinson’s disease (PD) Drosophila and mouse models. See pg.1, abstract.
Thus, the teachings of Marangos anticipate claims 1-3, 6-7, 13, 23-24, 26, 29-30 and 35.
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 6-7, 12-13, 21, 23-27, 29-30 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Marangos et al. (Published 16 February 1993, US-5187162-A, PTO-892) as evidenced by Liu et al. (Published 27 June 2023, The EMBO Journal, Vol. 42, Article No. e113410, pp. 1-20, IDS filed 12/08/2023).
Marangos as evidenced by Liu address claims 1-3, 6-7, 13, 23-24, 26, 29-30 and 35 as written in the 102 rejection above.
Although, Marangos does not expressly teach (a) the individual is a human as required in claim 12 and claim 27; (b) the additional therapeutic agent is levodopa, required claim 21; and (c) the contacting occurs in vitro, required in claim 25.
However, in the same filed of endeavor of treating Parkinson’s disease, withi respect to limitation (a), Marangos further teaches Parkinson’s disease in humans, see Col. 2, lines 10-15.
Marangos teaches current treatments of Parkinson’s disease involve symptom abatement with L-DOPA (e.g. levodopa, required in claim 21, i.e. limitation (b) discussed above), see Col. 12, lines 30-35.
Marangos also teaches compositions acceptable for pharmaceutical use are well known, see Col. 13, lines 19-20.
Therefore, with respect to limitation (a), the Examiner reasonably interprets the recitation of the individual as taught by Marangos above includes humans as required in claims 12 and 27.
With respect to limitation (b), it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have modified the method of Marangos to create a combination therapy comprising AICA riboside and/or AICA ribotide with L-DOPA as a treatment method for an individual affected by Parkinson’s disease because one of ordinary skill in the art would have been motivated to provide a combination therapy with AICA riboside and/or AICA ribotide which inhibits progressive deterioration in Parkinson’s disease patients and includes L-DOPA within said combination therapy in order to provide symptom abatement to Parkinson’s disease patients as explicitly taught by Marangos above.
One of ordinary skill in the art would have had a reasonable expectation of success to have modified the method of Marangos as discussed above, because Marangos teaches AICA riboside, AICA ribotide and L-DOPA are all useful agents in treating Parkinson’s disease patients as discussed above and that compositions acceptable for pharmaceutical use are well known as taught by Marangos as discussed above.
Additionally, the Examiner also respectfully notes MPEP 2144.06 states “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be used 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 (CCPA1980)(citations omitted).
With respect to limitation (c), the Examiner reasonably interprets this limitation to be a physical limitation that is well within the scope of the artisan because Marangos teaches administering the required agent to an individual with an LRRK2-associated disease or condition, specifically Parkinson’s disease, where the required agent can be taken up by cells in order to reduce or prevent neuronal cell death or neurodegeneration in said subject.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated limitations (a)-(c) as discussed above into the method as taught by Marangos above as well within the scope of the artisan as combining prior art elements according to known methods to yield predictable results as (a) Parkinson’s disease is a known disease in humans; (b) L-DOPA is a known treatment for Parkinson’s disease; and (c) contacting a cell with an agent is well within the scope of the artisan as discussed above.
One of ordinary skill in the art would have been motivated to incorporate limitations (a)-(b) in order to treat the individual affected by Parkinson’s disease; and limitation (c) in order to protect neuronal tissue against neurodegenerative damage which the Examiner respectfully notes are both taught by Marangos above. One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated limitations (a)-(c) into the method of Marangos above; because the Examiner respectfully reiterates (a) Parkinson’s disease is a known disease in humans; (b) L-DOPA is a known treatment for Parkinson’s disease; and (c) contacting a cell with an agent is well within the scope of the artisan as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the teachings of the prior art.
Conclusion
No claims are allowed in this action.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691