Prosecution Insights
Last updated: April 19, 2026
Application No. 18/382,562

METHODS OF TREATING TRANSTHYRETIN (TTR) MEDIATED AMYLOIDOSIS

Non-Final OA §103§DP
Filed
Oct 23, 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 §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 . Election/Restrictions Applicant’s election without traverse of Group II, claim 44, in the reply filed on 11/13/2025 is acknowledged. Claims 1, 4-11, 15, 39-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/13/2025. 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. Claim(s) 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alvarez et al (WO 2011/123468, October 2011, cited from IDS) and in further view of Hobo et al (Cancer Immunol Immunother, published online 19 August 2012, 62: 285-297). Alvarez teach siRNA for reducing expression of transthyretin (TTR) mRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, on page 100, such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Alvarez teach salts of such compounds (see lines 17-18 on page 19). Alvarez teach delivery of such siRNA using stable nucleic acid lipid particles (SNALP) in isotonic phosphate buffered saline, such SNALP can be a lipid formulation comprising lipids DLinDMA, PEG2000-C-DMA, DPPC and cholesterol (see lines 5-10 on page 121). Alvarez further teach different combinations and substitutions of lipids in SNALP formulation (see lines 11-12 on page 37, table bridging pages 40-41), such as lipid nanoparticle LNP11 comprising MC3 (same as instant Dlin-MC3-DMA), DSPC, cholesterol and PEG-DMG (see Table on page 41). Alvarez do not teach exactly the same mix of lipids as instantly claimed. Hobo teach lipid nanoparticles for siRNA delivery such as comprising cationic lipid DLin-MC3-DMA and DSPC, cholesterol, PEG2000-C-DMG (see “Preparation of LNP” portion in first column on page 287). It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to encapsulate siRNA taught by Alvarez in lipid nanoparticle taught by Hobo, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so to further improve delivery of siRNA as described by Alvarez using effective lipid nanoparticle described by Hobo, which is similar in composition to particles described by Alvarez. 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. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 8,168,775 in view of Hobo, above. Claims from ‘775 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Specification of ‘775 teaches delivery of siRNA in lipid formations (see lines 4-6 in column 3). Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 8,741,866 in view of Hobo, above. Claims from ‘866 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, in a lipid formation, such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 9,234,196 in view of Hobo, above. Claims from ‘196 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, in a lipid formation comprising MC3 (same as instant DLin-MC3-DMA), such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-53 of U.S. Patent No. 10,240,152 in view of Hobo, above. Claims from ‘152 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, in a lipid formation comprising MC3 (same as instant DLin-MC3-DMA), such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,227,744 in view of Hobo, above. Claims from ‘744 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, in a lipid formation comprising MC3 (same as instant DLin-MC3-DMA) and DSPC, such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,101,643 in view of Hobo, above. Claims from ‘643 recite siRNA with sense and antisense strands of SEQ ID NOs: 1009 and 1010, respectively, in a lipid formation comprising cationic lipid, such siRNA strands are identical to instantly claimed SEQ ID NOs: 1 and 2, respectively. Teachings of Hobo are discussed above. It would have been obvious to encapsulate siRNA of SEQ ID NOs: 1009-1010 in lipid formation taught by Hobo, arriving at instant invention. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,060,921. Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘921 recite patisiran, which is the same compound claimed in instant claim 44. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,079,379. Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘379 recite patisiran, which is the same compound claimed in instant claim 44. Claim 44 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11,806,360. Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘360 recite patisiran, which is the same compound claimed in instant claim 44. Claim 44 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 13-14, 18-20, 42-43, 46-48, 52-53, 55 of copending Application No. 17/672,771 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘771 recite patisiran, the same compound claimed in instant claim 44. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. 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

Oct 23, 2023
Application Filed
Dec 05, 2025
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
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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