Prosecution Insights
Last updated: April 19, 2026
Application No. 17/914,598

BETA-ARRESTIN COMPOSITIONS AND ASSOCIATED METHODS

Non-Final OA §101§102§112
Filed
Sep 26, 2022
Examiner
MACFARLANE, STACEY NEE
Art Unit
1675
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Duke University
OA Round
1 (Non-Final)
53%
Grant Probability
Moderate
1-2
OA Rounds
3y 5m
To Grant
92%
With Interview

Examiner Intelligence

Grants 53% of resolved cases
53%
Career Allow Rate
437 granted / 819 resolved
-6.6% vs TC avg
Strong +39% interview lift
Without
With
+38.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 5m
Avg Prosecution
42 currently pending
Career history
861
Total Applications
across all art units

Statute-Specific Performance

§101
10.1%
-29.9% vs TC avg
§103
23.9%
-16.1% vs TC avg
§102
19.2%
-20.8% vs TC avg
§112
34.7%
-5.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 819 resolved cases

Office Action

§101 §102 §112
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 . Response to Amendment Claims 1-2, and 4 have been amended as requested in the amendment filed on 23 January 2026. Following the amendment, claims 1-6, 8-11, 13-14, 16, and 20-30 are pending in the instant application. Election/Restrictions Applicant's election with traverse of Group I (claims 1-6 and 8-9) and the species of SEQ ID NO:7; beta 2 adrenergic receptor; and bioluminescence resonance energy transfer, in the reply filed on 23 January 2026 is acknowledged. The traversal is on the ground(s) that the Shenoy prior art does not disclose SUMO proteins. This is not found persuasive because the claims upon the Requirement for Restriction/Election did not recite SUMO proteins but ubiquitin-like protein, which is taught by Shenoy. Applicant’s amendment cannot obviate a Restriction Requirement made before the recitation of the newly added claim elements. The requirement is still deemed proper and is therefore made FINAL. Claims 3, 10-11, 13-14, 16, 20-24, and 29-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 23 January 2026. Claims 1-2, 4-6 and 8-9 are examined upon their merits. 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 1-2, 6 and 8-9 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 1 is indefinite wherein it recites the name “a small ubiquitin like modifier (SUMO)” as a limitation. It should be noted that there is no protein within the NIH protein database that has the name “SUMO” (see attached search report). There is a protein encoded by the gene SUMO1, which appears to be a preferred embodiment in the specification (see pg. 7 and Figure 5), however, claim 1 is not limited to this preferred embodiment. The specification states (paragraph [0048]): “SUMO and ubiquitin are ubiquitin-like proteins (UBLs), a family of small proteins involved in post-translational modification of other proteins in a cell” (emphasis added). Thus, the scope of “a [singular] small ubiquitin like modifier (SUMO)” is indefinite when read in light of the specification, and the metes and bounds of SUMO are indefinite. This affects the scope of all claims that fail to provide structure for this limitation, namely, claims 2, 6, 8 and 9. Claims 8-9 are rejected for recitation of intended effects without conferring some structural, material, or manipulative difference upon the scope of the parent claim, claim 1. Claim 8 recites, “The fusion protein of claim 1, wherein the fusion protein is resistant to de-SUMOylation”. It is unclear if this limitation is intending to further limit the protein of claim 1 by confer a different property. If so, it is unclear what material limitations are encompassed by the functional language of being “resistant to de-SUMOylation”. Further, the invention is directed to a product but this claim implies methodology; it is unclear if resistance to de-SUMOylation is required for direct infringement of this claim. Absent imposing a material or methodological difference upon the scope of claim 1, claim 8 will be interpreted as merely reciting a property of the fusion protein of claim 1, and prior art applicable to claim 1 will also read upon this claim. Similarly claim 9 is indefinite wherein it recites: “The fusion protein of claim 1, wherein the fusion protein displays increased binding to a G protein-coupled receptor (GPCR) upon expression in cells, wherein the increased binding is measured relative to the wild-type form of the arrestin polypeptide.” Claim 9 is indefinite because it recites a product and process in the same claim. MPEP 2173.05(p)(II) states: “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112, second paragraph.” See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303 (Fed. Cir. 2011). In Katz, a claim directed to “A system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data” was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. In re Katz, 639 F.3d at 1318 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited “an input means” and required a user to use the input means was found to be indefinite because it was unclear “whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means.”); < Ex parteLyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph). The case law applies to the instant claim(s) which recites a product that has increased binding relative to arrestin. It is unclear whether or not assessing increased binding to a GPCR is required for infringement because methodology is implicit, but there are no positively stated active steps. Absent method steps or a material difference that confers this increased binding, it is unclear how these claims further limit the scope of the protein recited in the parent claim. Absent a clear material or methodological difference upon the scope of claim 1, this claim will be interpreted as merely reciting a property of the fusion protein of claim 1, and any prior art applicable to claim 1 will also teach the invention of claim 9. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since these claims fail to meet all (3) criteria set forth in MPEP 2173.05(g), then Claims 8 and 9 are rejected. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-2, 5-6 and 8-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more. The claim(s) recite(s) an arrestin polypeptide fused to a small ubiquitin like modifier (SUMO) protein (claim 1); wherein the SUMO protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO:7 (claim 4); wherein the fusion protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO:1 or SEQ ID NO:2. The claimed product does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the arrestin polypeptide fused to a small ubiquitin like modifier (SUMO) protein, wherein the fusion protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO:1 or SEQ ID NO:2, is not markedly-different from its naturally-occurring counterpart. The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state, thus, the first step in the analysis is to select the appropriate counterpart(s) to the nature-based product. A pBLAST search for an amino acid sequence having at least 80% identity to SEQ ID NO:1 and at least 80% identity to SEQ ID NO:2 yields the following naturally-occurring proteins: Alignment with SEQ ID NO:1, which is 82% identical (see attached search report) PNG media_image1.png 580 819 media_image1.png Greyscale Alignment with SEQ ID NO:2, which is 97% identical (see attached search report) PNG media_image2.png 582 844 media_image2.png Greyscale The first result above (KAL1266690) is a naturally-occurring protein found in Cirrhinus molitorella (mud carp). The second result above (VTJ59087) is a naturally-occurring protein from Marmota monax (woodchuck). Both of these alignments “comprises an amino acid sequence having at least 80% identity to SEQ ID NO:1 or SEQ ID NO:2”, which fulfills the limitations of the instant claims. MPEP 2106.04(C)(ii)(A) states: “When there are multiple counterparts to the nature-based product, the comparison should be made to the closest naturally occurring counterpart. For example, assume that the inventor creates a cloned sheep D by transferring nuclear DNA from a Finn-Dorset sheep into an egg cell (which contains mitochondrial DNA) from a Scottish Blackface sheep. Applicant then claims sheep D. Here, because sheep D was created via combining DNA from two different naturally occurring sheep of different breeds, there is no single closest natural counterpart. The examiner should therefore select the counterpart most closely related to sheep D based on the examiner’s expertise in the particular art. For the example discussed here, the closest counterparts might be naturally occurring Finn-Dorset or Scottish Blackface sheep, as opposed to sheep of a different breed such as Bighorn sheep. Cf. Roslin, 750 F.3d at 1337, 110 USPQ2d at 1671-72. When the nature-based product is a combination produced from multiple components, the closest counterpart may be the individual nature-based components of the combination. For example, assume that applicant claims an inoculant comprising a mixture of bacteria from different species, e.g., some bacteria of species E and some bacteria of species F. Because there is no counterpart mixture in nature, the closest counterparts to the claimed mixture are the individual components of the mixture, i.e., each naturally occurring species by itself. See, e.g., Funk Bros., 333 U.S. at 130, 76 USPQ at 281.” The protein of the instant claims is a combination of two naturally-occurring polypeptides, namely, arrestin and small ubiquitin like modifier (hereafter SUMO). All conjoined peptides are linked by peptide bonds, thus fulfilling the peptide linker of instant claim 2. In light of this guidance pertaining to combinations of naturally-occurring products, there is no evidence that the fusion protein of the invention differs markedly in structure or function from the natural proteins of arrestin and SUMO. Since the naturally-occurring protein(s) aligned above, comprise at least 80% identity to the protein of the claimed invention, then the invention as claimed fails to markedly-differ from the nature-based product. Therefore, the invention of claims 1-2, 5-6 and 8-9. Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 1-2, 5-6 and 8-9 are rejected under 35 U.S.C. 102(a)(1), or in the alternative under 35 U.S.C. 102(a)(2), as being anticipated by . (hereafter “the ‘717 publication”), published 12 August 2004, and having an earliest effective US filing date (“effectively filed”) on 24 January 2003. It should be noted that the SUMO of the instant claims is a family of small proteins covalently attached to target proteins to regulate their function, location and stability. SUMO proteins are similar to ubiquitin and are considered members of the ubiquitin-like protein family. SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. Although SUMO has very little sequence identity with ubiquitin (less than 20%) at the amino acid level, it has a nearly identical structural fold. SUMO protein has a unique N-terminal extension of 10-25 amino acids which other ubiquitin-like proteins do not have. (See Wikipedia page for SUMO protein attached as search notes.) Regarding claims 1, 8, and 9, the ‘717 publication teaches a fusion protein comprising modified arrestins and arrestin chimeras. The arrestin chimeras include arrestins that have been modified by ubiquitination, that is, the addition of an ubiquitin molecule or moiety to the arrestin (pg. 1, lines 15-18). As stated in the rejection under 112 above, claims 8-9 are interpreted as reciting a property of the fusion protein of instant claim 1. Therefore, the ‘717 publication teaches the fusion protein of claims 8-9. Regarding claim 2, the ‘717 publication states: “The invention also relates to arrestin and ubiquitin that are expressed as a chimera linked via an amide bond at the 5' end of one protein to the 3' end of the other” (pg. 5, lines 3-5). Thus, the prior art teachers the arrestin polypeptide is fused to the ubiquitin protein via a peptide linker. Regarding claim 5, the ‘717 publication teaches a fusion protein comprising an amino acid sequence having at least 80% identity to SEQ ID NO:1 or SEQ ID NO:2. The alignment below depicts this fusion protein which is 84% similar to instant SEQ ID NO: 1. PNG media_image3.png 809 864 media_image3.png Greyscale Regarding claim 6, the ‘717 publication states, “The modified arrestin will have both an ubiquitin moiety and a label molecule attached to arrestin” (pg. 4, lines 2-3). The publication defines: “’Label molecule’ means any detectable molecule capable of improved detection by spectroscopic, photochemical, biochemical, immunochemical, radiochemical, electrical, and optical means, including but not limited to, fluorescence, phosphorescence, radioactivity, and bioluminescence when compared with the detection of the molecule to which the label molecule is attached. In one embodiment, the label molecule makes detection of the moiety it is attached to, e.g. the arrestin ubiquitin complex, easier than without the label molecule. Label molecules include, but are not limited to GFP, YFP, luciferase, rhodamine-conjugated antibody, and the like” (pg. 20, lines 16-24). Thus, the fusion protein of the prior art further comprises a detectable moiety. Thus, the invention of Claims 1-2, 5-6 and 8-9 fails to distinguish over the proteins disclosed in the prior art, and the claims are rejected. Allowable Subject Matter Claim 4 is 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. Conclusion No claim is allowed at this time. Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M.. 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, Jeffrey Stucker can be reached at 571-272-0911. 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. /STACEY N MACFARLANE/Examiner, Art Unit 1675
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Prosecution Timeline

Sep 26, 2022
Application Filed
Mar 12, 2026
Non-Final Rejection — §101, §102, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
53%
Grant Probability
92%
With Interview (+38.9%)
3y 5m
Median Time to Grant
Low
PTA Risk
Based on 819 resolved cases by this examiner. Grant probability derived from career allow rate.

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