Prosecution Insights
Last updated: April 19, 2026
Application No. 18/317,772

METHODS OF TREATING METACHROMATIC LEUKODYSTROPHY

Non-Final OA §103§DP
Filed
May 15, 2023
Examiner
SHIBUYA, MARK LANCE
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Genzyme Corporation
OA Round
1 (Non-Final)
32%
Grant Probability
At Risk
1-2
OA Rounds
3y 9m
To Grant
57%
With Interview

Examiner Intelligence

Grants only 32% of cases
32%
Career Allow Rate
51 granted / 158 resolved
-27.7% vs TC avg
Strong +25% interview lift
Without
With
+24.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
28 currently pending
Career history
186
Total Applications
across all art units

Statute-Specific Performance

§101
2.9%
-37.1% vs TC avg
§103
38.2%
-1.8% vs TC avg
§102
18.1%
-21.9% vs TC avg
§112
27.0%
-13.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 158 resolved cases

Office Action

§103 §DP
DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, 18317772, PG-Publication US20230398192, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-20 and 25 are pending. Election/Restrictions Claims 14-20, 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/8/2025. Claims 1-13 are examined herein. Priority The filing receipt, mailed , states that this application, filed , claims benefit of domestic priority benefit of 63/459,564, filed 04/14/2023 and claims benefit of 63/342,590, filed 05/16/2022. Information Disclosure Statement The information disclosure statements (IDS) submitted on 9/1/2023 and 12/8/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Claim Rejections - 35 USC § 103 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 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. 1. Claims 1-3, 25 are rejected under 35 U.S.C. 103 as being unpatentable over Hordeaux, WO2020227166, (US 20220228170, Serial No. 17608493); Davidson, WO2021102234A1, (of record, IDS) and Fogh, WO200298455. Hordeaux, WO2020227166 discloses Reference SEQ. ID. No. 2 (507 aa) being 100% identical to Instant SEQ. ID. No. 1 (507 aa); Reference SEQ. ID. No. 3 (1527 na) being 92.6% identical to Instant SEQ. ID. No. 2 (1530 na); Reference SEQ. ID. No. 10 (736 aa) being 100% identical to instant SEQ. ID. No: 9 (736 aa); Hordeaux, WO2020227166 teaches MLD is due to a deficiency in ARSA (p. 1, 1st §). Hordeaux teaches an recombinant AAV comprising an AAV9 capsid, here AAVhu68 and ARSA (p. 4, 5th §, p. 24, last §), VP3 (p. 26, 2ⁿᵈ §, p. 27, 2ⁿᵈ §), ARSA is identical to SEQ. ID. No. 1 of the application (p. 4, penultimate §-p.4, 1st §), the promoter is CB7 (p. 5, 2ⁿᵈ §, p. 6, 5th §, p. 75, last §-p. 76, 2ⁿᵈ §, example 1), WPRE (p. 22, last §, p. 23, 1st §, p. 37, last §, p. 38, 1st §), poly A (p. 22, last §, p. 37, last §), AAV2 ITRs (p. 39, 1st §, p. 76, last §), a vector (p. 5, 4th §), composition (p. 5, 4th §-last §). Hordeaux, teaches a method of treating a disease such as MDL (p. 6, 2ⁿᵈ §, p. 10, 2ⁿᵈ §, p. 16, last §, p. 17, penultimate §, p.34, last §-p. 35, 1st §), the administration is via direct injection in the cisterna magma (p. 10, penultimate §, p. 36, last §, p. 47, 1st §, p. 56, penultimate §) or intracerebroventricular (p. 48, 1st §-2ⁿᵈ §, p. 50, 2ⁿᵈ §, p. 56, 4th §). Hordeaux does not teach SEQ ID NO: 10 into the rAAV particles a targeting expression comprised within the expression cassette for arylsulfatase A (ARSA). Davidson, WO2021102234A1, (of record, IDS), throughout the publication and abstract, and at para [00115], teach “gene replacement therapy” for a condition amenable to gene replacement therapy, such as genetic diseases. Davidson, at para [0042]-[0069], recombinant AAV, or rAAV; at Tables 3, 6, disclose AAV9 targeting peptides for particular brain structures, including reference SEQ ID NO: 110, which has the same sequence as instant SEQ ID NO: 10, (“KGGGFHG”), as in claim 1, and which targets the brain and central nervous system, e.g., cerebral and cerebellar cortex. Davidson, WO2021102234 teaches SEQ. ID. No. 110 (7 aa) being 100% identical to SEQ. ID. No. 10 (7 aa); SEQ. ID. No. 143 (748 aa) being 99.1% identical to SEQ. ID. No. 12 (748 aa); 98.9% identical to SEQ. ID. No. 13 (611 aa) and 98.7% identical to SEQ. ID. No. 14 (546 aa) of the application. Davidson further discloses a recombinant AAV comprising such capsid (Tables 3, 6, [0005]- [0006], [0011]-[0012], [00168]), AAV2 ITR ([0056], [0063]), VP3 ([0060]), CB7 ([00138], [00144]), a polyA ([0069]), linker sequences ([0007], [0009]), codon optimization ([0098]), a pharmaceutical composition ([0017], [00123]-[00124]), a method of deliver a nucleic acid ([0018]-[0019], [0070]), and method to treat a genetic disease ([00114], [00118]) using gene replacement therapy. Davidson, at reference SEQ ID NO: 143, teach a mutant capsid protein that is a 98.8% query match to instant SEQ ID NO: 12, as in instant claim 5. Fogh, WO200298455, throughout the publication and abstract, teaches metachromatic leukodystrophy as caused by an autosomal recessive genetic defect in the lysosomal enzyme Arylsulfatase A, and at reference SEQ ID NO: 1, teaches the recombinant human Arylsulfatase A having the identical sequence to instant SEQ ID NO: 1, as in claim 2. Fogh teaches the preparation and introduction of recombinant Arylsulfatase A into a suitable vector to transform host cells for treatment of metachromatic leukodystrophy. It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined an nucleic acid having the sequence of SEQ ID NO:10, as taught by Davidson, into the expression cassette comprised within a vector with a targeting capsid, for expressing arylsulfatase A, as taught by Hordeaux and Fogh. One of ordinary skill in the art would have motivated to have combined a nucleic acid having the sequence of SEQ ID NO:10, into a expression cassette comprised within a rAAV vector for expressing arylsulfatase A, in order to express a peptide in the rAAV capsid for targeting cells of brain and central nervous, thereby treating inborn metachromatic leukodystrophy. 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 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 8-19, 28 and 31 of copending Application No. 18949540 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because references claims 1-4 claim rAAV particles comprising an expression cassette for expressing a disorder-related polypeptide capable of transducing cells of the CNS (ref claim 1); encoding an ARSA polypeptide (ref claim 2); a modified AAV9 capsid comprising a targeting peptide of SEQ ID NO: 10, (ref claim 3); which is flanked by linker sequences, (ref claim 4). Thus, at least reference claims 1-4 recite limitations of instant independent claim 1. The claims of the reference application recite various SEQ ID NOs that are also recited in the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion 1. Claims 2-13 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Instant SEQ ID NO: 11, as claimed in instant claim 4, is not found in the examined prior art. Instant SEQ ID NO: 12, as claimed in instant claim 6, is not found in the examined prior art. Instant SEQ ID NO: 2, as claimed in instant claim 7, is not found in the examined prior art. Instant SEQ ID NO: 8, as claimed in instant claim 12, is not found in the examined prior art. 2. The prior art made of record and not relied upon, but which is considered pertinent to the disclosure of the instant application: Wright, US 12,076,420, throughout the reference and abstract, and at reference SEQ ID NO 75, teach instant SEQ ID NO: 4, as in instant claim 8; at reference SEQ ID NO 76, teach instant SEQ ID NO: 5, as in instant claim 8; and at reference SEQ ID NO 36, teach instant SEQ ID NO: 7, as in instant claim 10. Schmidt, US 11,236,360, throughout the reference and abstract, and at reference SEQ ID NO 65, teach instant SEQ ID NO: 6, as in instant claim 9. Passini, US 10,821,154, throughout the reference and abstract, and at reference SEQ ID NO 7, teach instant SEQ ID NO: 15, as in instant claim 9. 3. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM. 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 (Doug) Schultz, can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. MARK L. SHIBUYA Primary Patent Examiner Art Unit 1631 /MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631
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Prosecution Timeline

May 15, 2023
Application Filed
Jan 07, 2026
Non-Final Rejection — §103, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
32%
Grant Probability
57%
With Interview (+24.9%)
3y 9m
Median Time to Grant
Low
PTA Risk
Based on 158 resolved cases by this examiner. Grant probability derived from career allow rate.

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