Prosecution Insights
Last updated: April 19, 2026
Application No. 18/302,855

METHODS AND COMPOSITIONS FOR TREATING PRIMARY HYPEROXALURIA

Non-Final OA §103§112§DP
Filed
Apr 19, 2023
Examiner
POLIAKOVA-GEORGAN, EKATERINA
Art Unit
1637
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Alnylam Pharmaceuticals, Inc.
OA Round
1 (Non-Final)
65%
Grant Probability
Favorable
1-2
OA Rounds
2y 8m
To Grant
81%
With Interview

Examiner Intelligence

Grants 65% — above average
65%
Career Allow Rate
434 granted / 668 resolved
+5.0% vs TC avg
Strong +16% interview lift
Without
With
+16.2%
Interview Lift
resolved cases with interview
Typical timeline
2y 8m
Avg Prosecution
55 currently pending
Career history
723
Total Applications
across all art units

Statute-Specific Performance

§101
5.4%
-34.6% vs TC avg
§103
28.6%
-11.4% vs TC avg
§102
22.8%
-17.2% vs TC avg
§112
24.2%
-15.8% vs TC avg
Black line = Tech Center average estimate • Based on career data from 668 resolved cases

Office Action

§103 §112 §DP
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 . 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. Claims 13 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second 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. Claim 13 recites the limitation "the dose" in the first line. There is insufficient antecedent basis for this limitation in the claim. There are several “doses” recited in each claims 2 and 7 on which claim 13 depends and it is not clear which one “the dose” refers to. Claim 14 recites the limitation "the dose" in the second line. There is insufficient antecedent basis for this limitation in the claim. There are several “doses” recited in each claims 2, 5, 7 and 10 on which claim 14 depends and it is not clear which one “the dose” refers to. 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. 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. Claim(s) 1-2, 4-7, 9-14, 25, 48-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erbe (WO 2019/014491, January 2019) and in further view of Cochat et al (The journal of pediatrics, 1999, volume 135, issue 6, pages 746-750), O’Hara (Aust Prescr., 2016, 39: 208-210) and Querbes et al (US 2017/0304446, October 2017). Erbe teaches methods of treatment of primary hyperoxaluria comprising administering double stranded RNAi agent that inhibits expression of HAO1 (see lines 10-15 on page 2), exemplifying the methods by administering double stranded siRNA AD-65585 with antisense strand of SEQ ID NO: 15 with all modified nucleotides (see lines 3-7 on page 101): usAfsuauUfuCfCfaggaUfgAfaagucscsa, wherein lower case letters refer to 2’-OMe modified nucleotides and nucleotides with “f” after nucleotide letter are 2’-F modified (see Table B). The sequence is identical to instant SEQ ID NO: 706. The sense strand of siRNA AD-65585 is fully modified as well and comprises GalNAc ligand attached at 3’ end, denoted L96: gsascuuuCfaUfCfCfuggaaauauaL96 (see lines 3-7 on page 101, Table B). GalNAc ligand is of the same structure as in instant claim 50 (see page 45, top structure). Further Erbe teaches a dosing regimen that includes loading phase of closely spaced administrations and maintenance phase, in which the siRNA is administered at longer spaced intervals (see lines 5-10 on page 95). Erbe teaches dosages of administration from 2 mg/kg to 5 mg/kg per kg of body weight of the subject (see lines 10-12 on page 55) and monthly administration (see lines 20-25 on page 94). Erbe teaches a variety of treatment regimens and methods of administration (see pages 58-59) and evaluation of activity of siRNA AD-65585 in different subjects, including humans (see Examples 2-4). Erbe do not teach treatment of pediatric subjects with specific dosages as instantly claimed or specific way of GalNAc conjugation as in instant claim 51. Cochat discuss primary hyperoxaluria in pediatric population, including infants, and potential management of the disease (see Abstract, page 746). O’Hara teach pharmacokinetics of drugs and drug doses in pediatric population based on child’s age and weight (see Abstract). Querbes teach conjugation of siRNAs targeting HAO1 to GalNAc through specific conjugate, identical to the one in instant claim 51 (see claim 31). It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to adjust treatment regimens taught by Erbe to treating pediatric subjects based on teachings of Cochat and O’Hara and use conjugation to GalNAc taught by Querbes, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so because Cochat teach that pediatric subjects suffer from primary hyperoxaluria, O’Hara suggests adjustments of treatment protocols applying to pediatric populations and Erbe teach the siRNA which successfully treats primary hyperoxaluria and methods of treatment of the disease in adults. Further, Querbes provides an example of successful conjugation of siRNAs targeted to HAO1, same as in Erbe, motivating one of the art to use the same conjugate as in Querbes. 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 1-2, 4-7, 9-14, 25, 48-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,478,500 in view of Erbe, Cochat and O’Hara, above. Claims from ‘500 recite the siRNA targeting HAO1 of the same sequence as Erbe, above. Teachings of Erbe, Cochat and O’Hara are discussed above. It would have been obvious to treat pediatric subjects with siRNA from ‘500 with a treatment regimen as in instant claims based on teachings of Erbe, Cochat and O’Hara. Claims 1-2, 4-7, 9-14, 25, 48-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,446,380 in view of Erbe, Cochat and O’Hara, above. Claims from ‘380 recite the siRNA targeting HAO1 of the same sequence as Erbe, above. Teachings of Erbe, Cochat and O’Hara are discussed above. It would have been obvious to treat pediatric subjects with siRNA from ‘380 with a treatment regimen as in instant claims based on teachings of Erbe, Cochat and O’Hara. Claims 1-2, 4-7, 9-14, 25, 48-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,261,447 in view of Cochat and O’Hara, above. Claims from ‘447 recite methods of treating of human subjects by conjugated siRNA with antisense strand comprising instant SEQ ID NO: 706. Teachings of Cochat and O’Hara are discussed above. It would have been obvious to modify methods from ‘447 for treatment of pediatric subjects with a treatment regimen as in instant claims based on teachings of Cochat and O’Hara. Claims 1-2, 4-7, 9-14, 25, 48-51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 18-41 of copending Application No. 17/579655 in view of Cochat and O’Hara, above. Claims from ‘655 recite methods of treating of human subjects by conjugated siRNA with antisense strand comprising instant SEQ ID NO: 706. Teachings of Cochat and O’Hara are discussed above. It would have been obvious to modify methods from ‘655 for treatment of pediatric subjects with a treatment regimen as in instant claims based on teachings of Cochat and O’Hara. This is a provisional nonstatutory double patenting rejection. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5. 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, Jennifer Dunston can be reached at (571)272-2916. 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. /EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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Prosecution Timeline

Apr 19, 2023
Application Filed
Mar 05, 2026
Non-Final Rejection — §103, §112, §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
65%
Grant Probability
81%
With Interview (+16.2%)
2y 8m
Median Time to Grant
Low
PTA Risk
Based on 668 resolved cases by this examiner. Grant probability derived from career allow rate.

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