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 instant application, U.S. Application Number 18/901,912, filed 30 September 2024 claims priority as a continuation of U.S. Application Number 17/327,562, filed 21 May 2021 (now U.S. Patent No. 12,133,897), which claims priority from provisional application 63/028,335, filed 21 May 2020.
Election/Restrictions
In the response filed on 8th of May 2026, Applicant's election of Group II, claims 4-14, with traverse is acknowledged. The traversal is on the ground(s) that there is no additional burden on the Examiner to search the composition claims (Remarks, page 4-5).
This is not found persuasive because US 35 U.S.C. 111(a) restriction practice is a USPTO procedure requiring an applicant to elect a single, patentably distinct invention when a single nonprovisional application claims multiple independent inventions. This process separates unrelated or distinct claims, ensuring the examiner faces no serious burden, while unelected claims are withdrawn from current examination. As stated in the restriction requirement filed 10th of Feb. 2026, the composition (of Invention I) can be used with alternative methods, such as target validation experiments for capsid engineering or surface modifications to improve targeting specific cells or cell culture methods involving culturing cells. Thus, the requirement is still deemed proper and is therefore made FINAL.
Status of Claims
In the response filed on 8th of May 2026, Applicant has amended claim 4, cancelled claims 1-3, and added new claim 15.
Currently, claims 4-15 are under examination in this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 25, 2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
It is noted that Applicants have not filed an information disclosure statement under §l.97(c). Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
Claim Objections
Claim 4 is objected to because of the following informalities: clarity of abbreviations. Claim 4 recites: “AAV” and it is suggested that the first recitation of AAV be “adeno-associated virus (AAV)”; “ITR” and it is suggested that the first recitation of ITR be “inverted terminal repeats”; “CBA promoter” and it is suggested that the first recitation of “CBA” be “chicken β actin (CBA) promoter” Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 4-7, 9, 11, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Manfredsson, Fredric P., et al. (Experimental neurology 207.2: 289-301; published 2007, cited IDS 4/25/2025, hereinafter as "Manfredsson").
The instant claims recite “a polynucleotide sequence that encodes SEQ ID NO:2” (claim 4, lines 7-8). According to Technology Center 1600 procedure the examiner is instructed to interpret this type of claim language broadly: Claim language such as “a polynucleotide sequence” comprise the full-length sequence of SEQ ID NO: 2 or any portion of SEQ ID NO: 2. This claim is anticipated by any polynucleotide sequence which is a portion of SEQ ID NO:2. If claim 4 were amended to recite “the polynucleotide sequence” the examiner would interpret the claims to encompass only a polynucleotide sequence that consists of the full length of SEQ ID: 2), with or without additional nucleotides at either or both ends. Such language would not be anticipated by the cited prior art. Therefore, the instant claims are anticipated by Manfredsson, Fredric P., et al., which teaches a method of modifying a cell comprising administering a pharmaceutical construct comprising a wild-type parkin (PARK2) gene, comprising a polynucleotide (abstract, Fig. 1, Experiment 2-3).
Regarding claim 4, Manfredsson discloses a method of modifying a cell comprising, administrating a pharmaceutical composition comprising a sequence was found to be identical to the wild-type human parkin (i.e. Genbank sequence AB009973)( (see e.g. abstract Experiments 1-3, page 290-291, fig. 1): an AAV5 vector and a pharmaceutically acceptable carrier, wherein the AAV5 vector comprises from 5' -3': a. an AAV2 ITR; b. a chicken-beta-actin (CBA) promoter; c. a PARK2 gene comprising a polynucleotide sequence; d. a SV 40 poly A tail; and e. an AA V2 ITR; wherein the AAV also comprises AAV5 cap genes (see e.g. page 290-291, fig.1), corresponding to the claim limitation of a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEO ID NO: 2 (see alignment below).
[AltContent: textbox ([img-media_image1.png]
Alignment of AB009973 (top strand) with SEQ ID NO: 2, where the different amino acid positions are P228S and F463Y)]
Regarding claim 5, Manfredsson discloses a method of treating Parkinson’s disease comprising administering the pharmaceutical composition of claim 4 (see e.g. abstract Experiments 1-3, page 290-291, fig. 1).
Regarding claim 6, Manfredsson discloses intracerebral injections of the pharmaceutical composition (see e.g. Experiments 1-3, page 291, col. 2, para. 2), corresponding to the claim limitations wherein the pharmaceutical composition is administered by intrathecal administration.
Regarding claim 7, Manfredsson discloses wherein the pharmaceutical composition is administered to the substantia nigra of the subject's brain (see e.g. page 291, col. 2, para. 2).
Regarding claim 9, Manfredsson discloses wherein the neurons are dopaminergic neurons (see e.g. abstract, page 289-298, Experiment 1-2).
Regarding claim 11, Manfredsson discloses a method of inhibiting degeneration or death of a dopaminergic neuron in a subject in need thereof, comprising administering the pharmaceutical composition of claim 4 to the brain of the subject (see e.g. abstract Experiments 1-3, page 290-298, fig. 1-5).
Regarding claim 14, , Manfredsson discloses wherein the dose is administered at least one time (see e.g. page 294-298, Experiments 1-3).
Thus, Manfredsson anticipates the instant claims.
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 4-15 are rejected under 35 U.S.C. 103 as being unpatentable over Manfredsson, Fredric P., et al. (Experimental neurology 207.2: 289-301; published 2007, cited IDS 4/25/2025; hereinafter as "Manfredsson") in view of Daewoong, Jo (US10662419B2, published 2018), Mandel, R. J., et al. (Proceedings of the National Academy of Sciences 94.25: 14083-14088, published 1997), Chiorini et al., (US6855314B1, published 2005, cited IDS 4/25/2025; hereinafter as “Chiorini”).
Regarding claim 4, Manfredsson discloses a method of modifying a cell comprising, administrating a pharmaceutical composition comprising a sequence was found to be identical to the wild-type human parkin (i.e. Genbank sequenceAB009973)(see sequence alignment below)(see e.g. abstract Experiments 1-3, page 290-291, fig. 1): an AAV5 vector and a pharmaceutically acceptable carrier, wherein the AAV5 vector comprises from 5' -3': a. an AAV2 ITR; b. a chicken-beta-actin (CBA) promoter; c. a PARK2 gene comprising a polynucleotide sequence; d. a SV 40 poly A tail; and e. an AA V2 ITR; wherein the AAV also comprises AAV5 cap genes (see e.g. page 290-291, fig.1). [AltContent: textbox ([img-media_image1.png]
Alignment of AB009973 (top strand) with SEQ ID NO: 2, where the different amino acid positions are P228S and F463Y)]
Manfredsson does not explicitly disclose a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEO ID NO: 2 (See alignment above).
However, the prior art of Daewoong discloses a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEO ID NO: 2 (see below, ABSS sequence Results date May 19, 2026, Database: pubpaa, Result 1, Query match 100%)(see e.g. col. 14, 403-404).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the wild-type PARK2 gene, as taught by Manfredsson, with a polynucleotide sequence that encodes SEQ ID NO: 2, as taught by Daewoong, with a reasonable expectation of success because one of ordinary skill in the art would know that the Parkin recombinant proteins (iCP-Parkin) are cell-permeable, which have been developed as a protein-based anti-neurodegenerative agent for efficient blood-brain barrier (BBB)-penetration to effectively deliver the recombinant protein into the brain (as taught by Daewoong, see e.g. abstract).
[AltContent: textbox ([img-media_image2.png])]Regarding claim 5, Manfredsson discloses a method of treating Parkinson’s disease comprising administering the pharmaceutical composition of claim 4 (see e.g. abstract Experiments 1-3, page 290-291, fig. 1).
Regarding claim 6, Manfredsson discloses intracerebral injections of the pharmaceutical composition (see e.g. Experiments 1-3, page 291, col. 2, para. 2), corresponding to the claim limitations wherein the pharmaceutical composition is administered by intrathecal administration.
Regarding claim 7, Manfredsson discloses wherein the pharmaceutical composition is administered to the substantia nigra of the subject's brain (see e.g. page 291, col. 2, para. 2).
Regarding claim 8 and 10, Manfredsson discloses wherein the administration results in the expression of the PARK2 gene in neurons (see e.g. page 296).
Manfredsson does not explicitly disclose wherein the administration results in expression of the PARK2 gene in glial cells that are astrocytes.
MPEP 2111.04 states “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met.” In the instant case, as discussed above, Manfredsson discloses the administration step, therefore the PARK2 genes would naturally result in expression of neurons and glial cells.
Furthermore, Manfredsson references the prior art of Mandel (see page 300), which discloses that a recombinant adeno-associated virus (rAAV) is capable of expression in glial cells (see e.g. abstract). Further, Mandel discloses glial cell expression was stable for over 10 weeks and that the use of rAAV can therefore promote functional delivery levels for degenerative models of Parkinson’s disease (see e.g. abstract). Additionally, the prior art of Chiorini discloses using AAV5 vectors for delivering and expression to glial cells that are astrocytes (see e.g. abstract, field of invention, fig. 9 and 14).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods of modifying a cell comprising a pharmaceutical composition, as taught by Manfredsson and Daewoong, with expression to glial cells that are astrocytes, as taught by Mandel and Chiorini, with a reasonable expectation of success because one of ordinary skill in the art would know that AAV5 vectors are able to delivering nucleic acids to glial cells that are astrocytes (as taught by Chiorini, see e.g. abstract, field of invention).
Regarding claim 9, Manfredsson discloses wherein the neurons are dopaminergic neurons (see e.g. abstract, page 289-298, Experiment 1-2).
Regarding claim 11, Manfredsson discloses a method of inhibiting degeneration or death of a dopaminergic neuron in a subject in need thereof, comprising administering the pharmaceutical composition of claim 4 to the brain of the subject (see e.g. abstract Experiments 1-3, page 290-298, fig. 1-5).
Regarding claim 12-13, Manfredsson discloses 1x1012 genome copies per milliliters (gc/ml)(see e.g. page 291).
Manfredsson does not explicitly disclose wherein the subject is dosed with 1x106 to 1x1014 viral genomes (vg) or 1x1011 vg .
However, the prior art of Chiorini discloses using AAV5 vectors for delivering 1.5x1010 vg (see e.g. col. 34, fig. 13).
Further, the following is noted from the MPEP: MPEP 2144.05: “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” In regards to overlapping ranges, MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, continuing in regards to ranges are close, “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
In the instant case, neither the specification nor Applicant have provided evidence of that the claimed dosage of the pharmaceutical between with 1x106 to 1x1014 viral genomes (vg)(i.e. 1x1011 vg) is critical, thus the teaching of about 1.5x1010 vg (see e.g. col. 34, fig. 13) as taught by Chiorini, renders the claimed dosage viral genome concentration of or 1x1011 vg as obvious.
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods of modifying a cell comprising a pharmaceutical composition, as taught by Manfredsson and Daewoong, with the viral genome dosage for the pharmaceutical composition, as taught by Chiorini, with a reasonable expectation of success because one of ordinary skill in the art would know that AAV5 vectors are able to delivered to cells of the central nervous system, such as glial cells that are astrocytes (as taught by Chiorini, see e.g. abstract, field of invention).
Regarding claim 14, , Manfredsson discloses wherein the dose is administered at least one time (see e.g. page 294-298, Experiments 1-3).
Regarding claim 15, as stated supra, Manfredsson discloses a method of treating Parkinson’s disease comprising administering the pharmaceutical composition of claim 4 (see e.g. abstract Experiments 1-3, page 290-291, fig. 1).
Manfredsson does not explicitly discloses the pharmaceutical composition comprising a lipid.
However, the prior art Daewoong discloses a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEO ID NO: 2, as stated supra, with a biologically active molecule such as lipids and glycolipids (see e.g. Technical solution section, col. 7).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the wild-type PARK2 gene, as taught by Manfredsson, with a polynucleotide sequence that encodes SEQ ID NO: 2 and a biologically active molecule, such as lipids, as taught by Daewoong, with a reasonable expectation of success because one of ordinary skill in the art would know that the Parkin recombinant proteins (iCP-Parkin) are cell-permeable, which have been developed as a protein-based anti-neurodegenerative agent for efficient blood-brain barrier (BBB)-penetration to effectively deliver the recombinant protein into the brain (as taught by Daewoong, see e.g. abstract and col. 7).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4-15 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 5, 8, 12-16 and 18 of U.S. Patent No. 12133897 B2 (Application No. 17/327,562; hereinafter as “’897 Patent”) in view of Manfredsson, Fredric P., et al. (Experimental neurology 207.2: 289-301; published 2007, cited IDS 4/25/2025; hereinafter as "Manfredsson"), and Daewoong, Jo (US10662419B2, published 2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed to a method of modifying a cell comprising, administrating the pharmaceutical composition comprising: an AAV5 vector and a pharmaceutically acceptable carrier, wherein the AAV5 vector comprises from 5' -3': a. an AAV2 ITR; b. a CBA promoter; c. a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEQ ID NO: 2; d. a SV 40 poly A tail; and e. an AAV2 ITR; wherein the AAV also comprises AAV5 cap genes (claim 4).
The ‘897 patent claims recite a method of treating, or ameliorating Parkinson's Disease or a symptom thereof in a patient in need thereof, comprising administering a pharmaceutical composition comprising an AAV5 vector comprising a gene therapy construct comprising a parkin (PARK2) gene comprising a polynucleotide that encodes the polypeptide sequence selected from SEQ ID NOs: 4 or 6, wherein the method comprises administering the pharmaceutical composition to the brain of the patient., and the method of claim 1, wherein the PARK2 gene is a variant PARK2 gene that encodes a variant parkin polypeptide having greater auto-ubiquitination than a wild type parkin polypeptide comprising SEQ ID NO: 2 (claims 1-2).
Both claims are direct to a pharmaceutical composition comprising an AAV5 vector.
The patented claims do not recite wherein the pharmaceutical composition comprises a lipid.
However, the addition of a lipid would have been obvious in view of the prior art Daewoong discloses a wild-type PARK2 gene comprising a polynucleotide sequence that encodes SEO ID NO: 2, as stated supra by Manfredsson and Daewoong, with a biologically active molecule such as lipids and glycolipids (see e.g. Technical solution section, col. 7).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have used the patented method in view of the teachings of the prior art of the wild-type PARK2 gene, as taught by Manfredsson, with a polynucleotide sequence that encodes SEQ ID NO: 2 and a biologically active molecule, such as lipids, as taught by Daewoong, with a reasonable expectation of success because one of ordinary skill in the art would know that the Parkin recombinant proteins (iCP-Parkin) are cell-permeable, which have been developed as a protein-based anti-neurodegenerative agent for efficient blood-brain barrier (BBB)-penetration to effectively deliver the recombinant protein into the brain (as taught by Daewoong, see e.g. abstract and col. 7). Therefore, the instant claims would have been obvious in view of the patented claims and the cited prior art. In addition, it would not be possible to use the instant claims without the compositions of the patented claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (EST).
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/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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