Prosecution Insights
Last updated: April 19, 2026
Application No. 18/359,483

PROTEIN BINDING DOMAINS STABILIZING FUNCTIONAL CONFORMATIONAL STATES OF GPCRS AND USES THEREOF

Non-Final OA §112§DP
Filed
Jul 26, 2023
Examiner
LI, RUIXIANG
Art Unit
1674
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Board Of Trustees Of The Leland Stanford Junior University
OA Round
1 (Non-Final)
59%
Grant Probability
Moderate
1-2
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 §DP
Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. DETAILED ACTION Status of Application, Amendments, and/or Claims 1. Claims 1-15 are pending and currently under consideration. Information Disclosure Statement 2. The information disclosure statement filed on 07/26/2023 and 03/05/2024 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to the office action. Drawings 3. The drawings filed on 07/26/2023 are accepted by the Examiner. Claim Rejections[Symbol font/0xBE]35 USC § 112, 1st paragraph 4. 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. 5. Claims 1-15 are rejected under 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. 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. Claim 1 is drawn to a complex comprising (i) a protein binding domain capable of specifically binding to an intracellular epitope of a GPCR and, upon binding, of stabilizes a conformation of the GPCR, wherein the protein binding domain comprises a nanobody sequence, or any stabilizing fragment thereof, and (ii) the GPCR. Claims 2-15 depend from claim 1. The claims do not require that the protein binding protein possess any particular conserved structure or any distinguishing feature. Thus, claims encompass an enormous genus of a complex comprising a protein binding protein without any structural features for the protein binding proteins. The specification disclosed that 16 nanobodies recognize native agonist-bound β2AR-365, but not the inverse agonist or the heat denatured receptor (Example 3). The specification discloses that seven of those antibodies possess G protein-like behavior and enhance the affinity of the β2AR for the agonist, isoproterenol (see, e.g., Examples 5-7). Such a disclosure is insufficient to support the broad genus of protein binding proteins. Vas-Cath Inc. v Mahurkar, 19 USPQ2d 1111 (Fed. Cir.1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purpose of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Adequate written description requires more than a mere statement that it is part of the invention are reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir.1991). An adequate written description of a chemical invention “requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir.2004); Regents of the Univ. of Cal. V. Eli Lilly & Co., Inc., 119 F.3d 1559, 1556 (Fed. Cir.1997); Fiers v. Revel, 984F.2d 1164, 1171 (Fed. Cir.1993). “A description of what a material does, rather than of what it is, usually does not suffice.” Rochester, 358F.3d at 923; Eli Lilly, 119 F.3d at 1568. In addition, possession of a genus “may be achieved by means of a recitation of a representative number of [compounds]…falling within the scope of the genus.” Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 f. 3d at 927. Due to the breadth of the recited genus of protein binding proteins, and lack of the definitive structural and functional features of the recited genus, one skilled in the art would not recognize from the disclosure that Applicant was in possession of the recited genus of protein binding proteins and the complex comprising the protein binding proteins. Claim Rejections[Symbol font/0xBE] Nonstatutory Obviousness-Type Double Patenting 6. Basis for nonstatutory 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. See 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);and, 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/ guidance/eTD-info-I.jsp. 7. Claims 1-15 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-18 of US Patent No. 9,453,065 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. Claims 1-18 of US Patent No. 9,453,065 B2 are drawn to a complex comprising a nanobody able to specifically bind to and stabilize an active conformational state of a beta 2 adrenergic receptor (β2AR), wherein the nanobody is able to enhance the affinity of the β2AR for an agonist, and β2AR in an active conformational state. On the other hand, claims 1-15 of the instant application are drawn to complex comprising (i) a protein binding domain capable of specifically binding to an intracellular epitope of a G-Protein Coupled Receptor (GPCR) and, upon binding, of stabilizes a conformation of the GPCR, wherein the protein binding domain comprises a nanobody sequence, or any stabilizing fragment thereof; and (ii) the GPCR. Thus, claims 1-18 of US Patent No. 9,453,065 B2 are related to claims 1-15 of the instant application as species to genus with respect to GPCR and protein binding domain (nanobody). A species renders its genus obvious and thus anticipates the genus. Conclusion 8. No claims are allowed. Advisory Information 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 2, 2026
Read full office action

Prosecution Timeline

Jul 26, 2023
Application Filed
Feb 02, 2026
Non-Final Rejection — §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
59%
Grant Probability
78%
With Interview (+19.0%)
2y 10m
Median Time to Grant
Low
PTA Risk
Based on 1015 resolved cases by this examiner. Grant probability derived from career allow rate.

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