Prosecution Insights
Last updated: April 19, 2026
Application No. 17/486,394

COMPOSITIONS AND METHODS FOR GENETICALLY-ENCODED HIGH VOLTAGE-ACTIVATED CALCIUM CHANNEL BLOCKERS USING ENGINEERED UBIQUITIN LIGASES

Final Rejection §112
Filed
Sep 27, 2021
Examiner
LI, RUIXIANG
Art Unit
1674
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Trustees of Columbia University in the City of New York
OA Round
5 (Final)
59%
Grant Probability
Moderate
6-7
OA Rounds
2y 10m
To Grant
78%
With Interview

Examiner Intelligence

Grants 59% of resolved cases
59%
Career Allow Rate
602 granted / 1015 resolved
-0.7% vs TC avg
Strong +19% interview lift
Without
With
+19.0%
Interview Lift
resolved cases with interview
Typical timeline
2y 10m
Avg Prosecution
29 currently pending
Career history
1044
Total Applications
across all art units

Statute-Specific Performance

§101
1.4%
-38.6% vs TC avg
§103
25.8%
-14.2% vs TC avg
§102
15.8%
-24.2% vs TC avg
§112
34.8%
-5.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1015 resolved cases

Office Action

§112
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 Status of Application, Amendments, and/or Claims Applicant's amendment filed on 02/05/2026 has been entered. Claims 50-62 and 89-98 are pending and under consideration. In response to species election requirement, Applicant elected without traverse the nanobody comprising SEQ ID NOS:83-85, which corresponds to SEQ ID NO: 86 in the reply filed on 03/07/2025. Claim Rejections under 35 USC § 112 (a) (i). The following is a quotation of the first paragraph of 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. (ii). Claims 50-52, 59, 62, and 89-94 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention. The basis for the rejection is set forth in the office action mailed on 02/05/2026. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Claims 50-52, 59, 62, and 89-94 are dawn to a composition comprising a nucleic acid molecule encoding a polypeptide comprising (i) an E3 ubiquitin ligase operably connected to (ii) a nanobody capable of binding to a Cavβ auxiliary subunit. The claims do not require that the nanobody possess any particular conserved structure nor other disclosed distinguishing feature. Thus, the claims encompass a genus of nanobodies capable of binding to a Cavβ auxiliary subunit without any structural features. For each claim drawn to a genus, MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”. In the instant case, the specification discloses nanobodies capable of binding to a Cavβ auxiliary subunit (page 4, paragraph [0011]; page 16, paragraph [0045]-[0046]). However, each nanobody that binds to a Cavβ auxiliary subunit has a particular set of three CDRs. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other nanobodies might be. Thus, the instant disclosure and prior art do not adequately support the genus of nanobodies binding to a Cav3 auxiliary subunit. Due to the breadth of the genus of the Cavβ auxiliary subunit nanobodies and lack of the definitive structural features of the genus, one skilled in the art would not recognize from the disclosure that Applicant was in possession of the genus of the Cavβ auxiliary subunit nanobodies and thus a composition comprising a nucleic acid molecule encoding a polypeptide comprising a nanobody capable of binding to a Cavβ auxiliary subunit. Response to Applicant’s argument Applicant argues that the amended claims require that the nanobody possess a disclosed distinguishing feature, “wherein the nanobody is functionally inert on the calcium channel”, which narrows the genus to nanobodies that bind Cavβ subunits without disrupting channel activity. Applicant argues that the claims as amended satisfy at least actual reduction to practice, by disclosure of relevant, identifying characteristics, and by functional characteristics coupled with a known or disclosed correlation between function and structure, and are sufficient to show the applicant was in possession of the claimed genus. Applicant’s argument has been fully considered but is not deemed to be persuasive because the recited function only indicates what the nanobody does but does not show what the nanobody is. Applicant argues that the instant specification provides complete structural disclosure of nanobodies capable of binding Cavβ auxiliary subunits. As disclosed at paragraph [0044], "twenty-five unique Cavβ-targeted nanobodies were developed and identified based on the unique sequences within complementarity determining regions (CDR1-3), the major determinants of antigen binding." These twenty-five unique Cavβ-targeted nanobodies represent at least seven structurally distinct classes of nanobody binders that could qualify for use in claim 50 as presently amended. Citing MPEP § 2163, Applicant argues that the development and selection process of the 25 disclosed nanobodies, which represent at least 7 distinct classes of nanobody binders, were specifically developed through an experimental process designed to identify functionally inert nanobodies capable of binding Cavβ auxiliary subunits. Applicant argues that this case is distinguishable from AbbVie Deutschland GmbH &Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014), as cited in our previous response of October 28, 2025. In Abb Vie, claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus." In this instant application, the specification discloses 25 structurally diverse nanobodies representing at least seven distinct structural classes, as opposed to "one type of structurally similar antibodies" and extensively details methods to assay functional inertness of the nanobody in multiple cell types. Applicant’s argument has been fully considered but is not deemed to be persuasive. For each claim drawn to a genus, MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”. In the instant case, claims 50-52, 59, 62, and 89-94 claim 50 do not require that the nanobody possess any particular conserved structure nor other disclosed distinguishing feature. Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus." (AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014). In the instant application, the specification discloses that 25 nanobodies were produced by immunizing a llama with purified Cavβ1b and Cavβ3 (page 24, paragraph [0079]; Example 2; Table 1). The specification does not disclose the epitopes that these 25 nanobodies bind. One of skills in the art would understand that claims directed to nanobodies are not supported by a disclosure of 25 nanobodies that bind only to the same epitope or a limited number of epitopes within Cavβ1b or Cavβ3. In view of the factors, the at least seven members of Cavβ auxiliary subunits (page 11, paragraph [0034]), the mere use of Cavβ1b and Cavβ3 as immunogens, lack of disclosure of the epitopes that the 25 nanobodies bind, and the complexity of the binding characteristic recited in claims 51 and 52, as well as the cases law cited by Applicant, the limited number of 25 nanobodies does not represent a representative number of species of nanobodies capable of binding to a Cavβ auxiliary subunit. Thus, the instant disclosure is insufficient to support the genus of the Cavβ auxiliary subunit nanobodies and a composition comprising a nucleic acid molecule encoding a polypeptide comprising a nanobody capable of binding to a Cavβ auxiliary subunit. Therefore, the rejection is maintained. Claim Objections (i). Claims 54-55, 57-58, and 60-61 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. (ii). Claims 53, 56, and 95-98 are objected to because they recite non-elected subject matter. Conclusion No claims are allowed. Advisory Information THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, please contact the Electronic Business Center (EBC) at the toll-free phone number 866-217-9197. /RUIXIANG LI/Primary Examiner, Art Unit 1674 February 17, 2026
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Prosecution Timeline

Sep 27, 2021
Application Filed
Apr 18, 2025
Non-Final Rejection — §112
Jul 18, 2025
Response Filed
Jul 30, 2025
Final Rejection — §112
Oct 28, 2025
Request for Continued Examination
Oct 29, 2025
Response after Non-Final Action
Nov 06, 2025
Non-Final Rejection — §112
Nov 11, 2025
Non-Final Rejection — §112
Feb 05, 2026
Response Filed
Feb 17, 2026
Final Rejection — §112 (current)

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Prosecution Projections

6-7
Expected OA Rounds
59%
Grant Probability
78%
With Interview (+19.0%)
2y 10m
Median Time to Grant
High
PTA Risk
Based on 1015 resolved cases by this examiner. Grant probability derived from career allow rate.

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