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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 23, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed June 23, 2026 is acknowledged. Claims 4 and 6-8 are cancelled. Claims 1 and 11-12 are amended. Claim 13 is newly added. Claims 1-3, 5, 9-12 and new claim 13 are pending in this application and under examination in this office action.
4. Applicant’s arguments filed on June 23, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
5. The rejection of claims 4 and 6-8 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is moot because the claims are canceled.
The rejection of claims 1-12 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 4 and 6-8.
Claim Rejections/Objections Maintained
In view of the amendment filed on June 23, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 112
6. 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 1-3, 5 and 9-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling restoring carbonyl cyanide 3-chlorophenyihydrazone (CCCP)-induced mitophagy or restoring impaired parkin-mediated mitophagy caused by heterozygous or homozygous mutations in parkin gene or increasing Nix-mediated mitophagy or rescuing mitochondrial function in cells of patients with Parkinson’s disease associated with impaired parkin-mediated mitophagy by a. identifying a subject having impaired parkin-mediated mitophagy, and administering an agent comprising the claimed Nix polypeptide or an expression vector encoding the Nix polypeptide thereof or in combination with the claimed GABARAP-L1 polypeptide or an expression vector encoding the GABARAP-L1 polypeptide thereof, does not reasonably provide enablement for a method for treating Parkinson’s disease associated with Impaired parkin-mediated mitophagy in a subject as broadly claimed. 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. In addition, the specification does not enable the invention of claims 1-3, 5 and 9-13 that is directed to a method of prevention. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-3, 5 and 9-13 as amended are drawn to a method for treating Parkinson’s disease (PD) associated with impaired parkin-mediated mitophagy in a subject, comprising:
a. identifying a subject as having impaired parkin-mediated mitophagy, and
b. administering to the subject a therapeutically effective amount of an agent that increases Nip3-like protein X (Nix)-mediated mitophagy in a cell, wherein the agent comprises a Nix polypeptide having at least 95%, 98%, 99% or 100% sequence identity to the amino acid sequence set out in SEQ ID NO:1 and having Nix biological activity; or an expression vector encoding the Nix polypeptide.
The claims encompass a method of treating and preventing PD associated with impaired parkin-mediated mitophagy using an agent comprising a Nix polypeptide or a variant thereof with at least 95%...100% identity to instant SEQ ID NO:1, or an expression vector thereof; or in combination with a GABARAP-L1 polypeptide or a variant thereof with at least 95% identity to instant SEQ ID NO:3, or an expression vector thereof.
Response to Arguments
On p. 4-6 of the response, Applicant argues that: i) the rejection has been overcome in view of amendment to the claims by reciting “treating Parkinson’s disease associated with impaired parkin-mediated mitophagy” and specific Nix and GABARAP-1 sequences; ii) the specification provides support and cites paragraphs [0017],[0040], [000117]; [00032]; [00034]; [000102]; and “overexpression of Nix restores CCCP-induced cells lacking functional parkin and cells of an individual carrying homozygous mutation in PINK1 (see [000275]; [000276].
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2164, MPEP §§2164.01-2164.06(b) & 2164.08, neither the specification nor the prior art provides sufficient guidance to enable a skilled artisan to practice the claimed invention without undue experimentation because:
i. The claims as amended encompass a method of treating and preventing PD associated with impaired parkin-mediated mitophagy by the claimed agent because based on paragraphs [0073]-[0074] of the published Application, the definition of “treating” encompasses preventing PD.
[0073] As used herein, the terms “treatment” or “treating” mean: (1) improving or stabilizing the subject's condition or disease or (2) preventing or relieving the development or worsening of symptoms associated with the subject's condition or disease.
[0074] As used herein, the terms “prevent,” “preventing,” “prevention,” and the like refer to reducing the probability of developing a disorder or condition in a subject, who does not have, but is at risk of or susceptible to developing a disorder or condition.
However, neither the specification nor the prior art provides guidance as to how to prevent a person from getting PD associated with impaired parkin-mediated mitophagy by the claimed agent before the disorders occur.
The specification provides no guidance that administration of the claimed agent comprising a Nix polypeptide, variant thereof with at least 95% identity to SEQ ID NO:1 or an expression vector thereof or in combination with a GABARAP-L1 polypeptide or a variant thereof with at least 95% identity to instant SEQ ID NO:3, or an expression vector thereof can prevent a person from getting PD associated with impaired parkin-mediated mitophagy. PD cannot be prevented as evidenced by Oertel (F1000Res. 2017 Mar 13;6:260; see p.2, second paragraph).
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, limited working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by a skilled artisan to perform in order to practice the claimed invention as it pertains to a method for treating PD associated with impaired parkin-mediated mitophagy in a subject by administration of the claimed agent comprising a Nix polypeptide or a variant thereof with at least 95%...100% identity to instant SEQ ID NO:1, or an expression vector thereof; or in combination with a GABARAP-L1 polypeptide or a variant thereof with at least 95% identity to instant SEQ ID NO:3, or an expression vector thereof.
Accordingly, the rejection of claims 1-3, 5 and 9-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is maintained.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on June 23, 2026.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 5 and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Rubinsztein (WO2004/089369 as in IDS) in view of Deas et al. (Biochimica et Biophysica Acta, 2011; 1813:623-633, as in IDS).
Claims 1-3, 5, 9-13 as amended are drawn to a method for treating Parkinson’s disease (PD) associated with impaired parkin-mediated mitophagy in a subject, comprising:
a. identifying a subject as having impaired parkin-mediated mitophagy, and
b. administering to the subject a therapeutically effective amount of an agent that increases Nip3-like protein X (Nix)-mediated mitophagy in a cell, wherein the agent comprises a Nix polypeptide having at least 95%, 98%, 99% or 100% sequence identity to the amino acid sequence set out in SEQ ID NO:1 and having Nix biological activity; or an expression vector encoding the Nix polypeptide.
The rejection is based on what is enabled within the claims set forth above under the 112(a) rejection.
Rubinsztein teaches a method for treating a neurodegenerative disorder associated with impaired parkin-mediated mitophagy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an agent that increases Nix-mediated mitophagy in a cell, i.e. rapamycin (see e.g. abstract), and wherein the cell can be a neuron (see e.g. p.57, lines 21-30); and wherein the neurodegenerative disorder is associated with mitochondrial dysfunction, including PD (mutation in parkin gene, which causes reduced expression of parkin and/or PINK1) (see p.4, lines 29-33) and early stage PD.
But Rubinsztein does not teach the step of identifying impaired parkin-mediated mitophagy or that the agent is a Nix polypeptide or a GABARAP-L1 polypeptide or an expression vector thereof recited in claim 1.
Deas et al. teaches that mitochondrial dysfunction is an early sign of many neurodegenerative diseases and that two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy) (p. 628, 2nd col, section: 6. Mitophagy and neurodegenerative disease to p..630). Deas teaches that PD-associated Parkin mutations results in reduced expression of parkin and/or PINK and interfering with the process of mitophagy at distinct steps as in claims 9-10 (see p. 629, 1st col., 3rd paragraph to 2nd col) and that Nix interacts with or recruitsGABRAPL1 and mediates the removal of damaged mitochondria, and that Nix translocates the PD-associated protein parkin to mitochondria, and the potential use of Nix and GABRAPL1 polypeptides and vectors encoding the polypeptides as in claims 2-3 and 11-12 (p. 630, 1st col.). The teaching of Deas provides motivation and an expectation of success in identifying PD patients having impaired parkin-mediated mitophagy, and that PD is associated with mitochondrial dysfunction and the role and function of Nix recruiting GABRAPL1 in mediating the removal of damaged mitochondria, and translocation of the PD-associated protein parkin to mitochondria.
A person of ordinary skill in the art would have recognized that selecting and applying the known Nix polypeptide or in combination with the known GABRAPL1 polypeptide and the known technique disclosed by Deas to the Rubinsztein’s method would have yielded the predictable result of increasing Nix-mediated mitophagy and restoring impaired parkin-mediated mitophagy caused by heterozygous or homozygous mutations in parkin gene or rescuing mitochondrial function in cells of patients with Parkinson’s disease associated with impaired parkin-mediated mitophagy.
Using Nix polypeptide or in combination with GABRAPL1 polypeptide in the Rubinsztein’s method would increase Nix-mediated mitophagy, restore impaired parkin-mediated mitophagy caused by mutations in parkin gene and rescueg mitochondrial function in in cells of patients with PD associated with impaired parkin-mediated mitophagy, and expand application of the Rubinsztein’s method, and would increase patient’s satisfaction with treatment based on increasing Nix-mediated mitophagy because the function of Nix is to translocate the PD-associated protein parkin to mitochondria, interact with or recruitGABRAPL1 and mediates the removal of damaged mitochondria and increasing the levels of Nix polypeptide or in combination with GABRAPL1 polypeptide would enhance the process of translocating the PD-associated protein parkin to mitochondria, increase Nix-mediated mitophagy and restore impaired parkin-mediated mitophagy caused by mutations in parkin gene and rescue mitochondrial function in cells of patients with PD associated with impaired parkin-mediated mitophagy.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known Nix polypeptide or in combination with the known GABRAPL1 polypeptide and the known technique disclosed by Deas to the Rubinsztein’s method, and yield the predictable result of increasing Nix-mediated mitophagy and restoring impaired parkin-mediated mitophagy caused by heterozygous or homozygous mutations in parkin gene or rescuing mitochondrial function in in cells of patients with PD associated with impaired parkin-mediated mitophagy.
Claim Rejections - 35 USC § 103
8. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Rubinsztein (WO2004/089369) in view of Deas et al. (Biochimica et Biophysica Acta, 2011; 1813:623-633) as applied to claims 1-3, 5 and 9-12 above, and further in view of Grenier et al. (Front Neurol, 2013;4:100.doi:10.3389/fneur.2013.00100).
Rubinsztein and Deas are set forth above but fail to teach early onset PD (EOPD).
Grenier et al. teach that early onset PD is caused by mutations in PINK1 and/or parkin and the loss of parkin or PINK1 leads to an early onset form of PD and impaired parkin/PINK1-mitophagy.
A person of ordinary skill in the art would have recognized that selecting and applying the known knowledge that early onset PD is caused by mutations in PINK1 and/or parkin and the loss of parkin or PINK1 leads to an early onset form of PD and impaired parkin/PINK1-mitophagy disclosed by Grenier to the method of Rubinsztein and Deas to treat early onset PD would have yielded the predictable result of increasing Nix-mediated mitophagy and restoring impaired parkin-mediated mitophagy caused by heterozygous or homozygous mutations in parkin gene or rescuing mitochondrial function in cells of patients with early onset PD associated with impaired parkin-mediated mitophagy.
Treating early onset PD in the method of Rubinsztein and Deas would increase Nix-mediated mitophagy, restore impaired parkin-mediated mitophagy caused by mutations in parkin gene and rescue mitochondrial function in in cells of patients with early onset PD, and expand application of the method of Rubinsztein and Deas, and would increase patient’s satisfaction with treatment based on increasing Nix-mediated mitophagy because early onset PD is caused by mutations in PINK1 and/or parkin and the loss of parkin or PINK1 leads to an early onset form of PD and impaired parkin/PINK1-mitophagy as taught by Grenier, and the increased levels of Nix polypeptide or in combination with GABRAPL1 polypeptide would enhance the process of translocating the PD-associated protein parkin to mitochondria, increase Nix-mediated mitophagy and restore impaired parkin-mediated mitophagy caused by mutations in parkin gene and rescue mitochondrial function in cells of patients with PD associated with impaired parkin-mediated mitophagy.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known knowledge that early onset PD is caused by mutations in PINK1 and/or parkin and the loss of parkin or PINK1 leads to an early onset form of PD and impaired parkin/PINK1-mitophagy disclosed by Grenier to the method of Rubinsztein and Deas to treat early onset PD, and yield the predictable result of increasing Nix-mediated mitophagy and restoring impaired parkin-mediated mitophagy caused by heterozygous or homozygous mutations in parkin gene or rescuing mitochondrial function in in cells of patients with PD associated with impaired parkin-mediated mitophagy.
Conclusion
9. NO CLAIM IS ALLOWED.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
July 25, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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