Prosecution Insights
Last updated: April 19, 2026
Application No. 17/504,500

GLP-1R AGONIST REDUCES RETINAL INFLAMMATION AND NEURON DEATH SECONDARY TO OCULAR HYPERTENSION

Final Rejection §102§103
Filed
Oct 18, 2021
Examiner
BRADLEY, CHRISTINA
Art Unit
1654
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Trustees of the University of Pennsylvania
OA Round
6 (Final)
63%
Grant Probability
Moderate
7-8
OA Rounds
2y 10m
To Grant
96%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allow Rate
638 granted / 1018 resolved
+2.7% vs TC avg
Strong +33% interview lift
Without
With
+32.9%
Interview Lift
resolved cases with interview
Typical timeline
2y 10m
Avg Prosecution
50 currently pending
Career history
1068
Total Applications
across all art units

Statute-Specific Performance

§101
4.8%
-35.2% vs TC avg
§103
28.4%
-11.6% vs TC avg
§102
23.3%
-16.7% vs TC avg
§112
23.2%
-16.8% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1018 resolved cases

Office Action

§102 §103
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 § 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, 4-6, 13, 15-18, 20-22, 29, 33-34, 36-38, 45, and 51-53 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Sinclair (US 2024/0024427 A1). Sinclair teaches a method of reducing intraocular pressure (IOP) in a subject, wherein the method comprises administering the GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof to the subject, to treat a disorder associated with intraocular pressure, such as a disorder associated with elevated IOP (¶ [0008]-[0009]). Sinclair teaches that the GLP-1 receptor agonist is preferably liraglutide, dulaglutide, or semaglutide (¶ [0076]). Sinclair teaches that the GLP-1 receptor agonists reduce IOP and, independently provide a neuroprotective effect. Sinclair teaches that the GLP-1 receptor agonists reduce IOP and prevent progressive loss of retinal ganglion cells (¶ [0103]). Therefore, Sinclair teaches all of the limitations of instant claims 1-2. With respect to claim 4, Sinclair teaches reducing the IOP in the subject by at least 30% from baseline and to less than 21 mmHg (¶ [0096]). With respect to claims 5-6, Sinclair teaches that the GLP-1 receptor agonist can be combined with administration of a prostaglandin derivates (such as bimatoprost, latanoprost, tafluprost, latanoprostene bunod and travoprost), adrenergic antagonist (such as betaxolol, carteolol, levobunolol, metipranolol, timolol maleate and timolol hemihydrate), adrenergic agonists (such as apraclonidine and brimonidine), carbonic anhydrase inhibitors (such as dorzolamide, brinzolamide, methazolamide and acetazolamide), Rho kinase inhibitors (such as netarsudil and ripasudil), or combinations thereof (¶ [0125]). With respect to claim 13, Sinclair teaches that the GLP-1 receptor agonist can be combined with glaucoma surgery (¶ [0046]). With respect to claims 15-16, Sinclair teaches reducing the IOP in the subject by at least 30% from baseline and to less than 21 mmHg (¶ [0096]). With respect to claims 17-18, 20-22, 29, 33-34, 36-38, and 45, the reference is silent on the effect on production of IL-l, TNF-, and Clq by CD11b+ CD11c+ and CD11b+ CD11c- cells, and transformation of astrocytes to an Al neurotoxic phenotype and activation of the Al astrocytes. These effects are inherent to the prior art method which teaches administering the same active agent, to the same patients, in the same manner as in the instant claims. With respect to claims 51-53, Sinclair teaches that the GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof as described herein is administered by means of subcutaneous administration (¶ [0083]). Response to Arguments In the response filed December 17, 2025, Applicant invokes the prior art exception under AIA 35 U.S.C. 102(b)(2)(B), which provides that a disclosure shall not be prior art to a claimed invention under AIA 35 U.S.C. 102(a)(2) if the subject matter disclosed had, before such subject matter was effectively filed under AIA 35 U.S.C. 102(a)(2), been publicly disclosed by the inventor or a joint inventor. In order to invoke this exception, Applicant must show that the subject matter disclosed had been publicly disclosed by the inventor or a joint inventor before the disclosure or effective filing date of the subject matter on which the rejection was based by way of an affidavit or declaration under 37 CFR 1.130(b) (an affidavit or declaration of prior public disclosure). Specifically, the affidavit or declaration must identify the subject matter publicly disclosed and establish the date and content of their earlier public disclosure. See MPEP § 2155.02. No affidavit or declaration has been filed. Therefore, the reference is not disqualified as prior art. In addition, Applicant should consider MPEP § 2154.02(b) which states: “The exception in AIA 35 U.S.C. 102(b)(2)(B) applies only to the subject matter in the intervening U.S. patent document being relied upon for a rejection under AIA 35 U.S.C. 102(a)(2) that was also publicly disclosed by the inventor or a joint inventor (or another who obtained the subject matter directly or indirectly from the inventor or joint inventor) before the date the subject matter relied upon was effectively filed. The subject matter of an intervening U.S. patent document that was not previously publicly disclosed by the inventor or a joint inventor (or by another who obtained the subject matter from the inventor or joint inventor) is available as prior art under AIA 35 U.S.C. 102(a)(2). For example, if the inventor or a joint inventor had publicly disclosed A, B, and C, and a subsequent intervening U.S. patent document discloses A, B, C, and D, then D of the intervening U.S. patent document remains available as prior art under AIA 35 U.S.C. 102(a)(2). In other words, the exception in AIA 35 U.S.C. 102(b)(2)(B) does not necessarily remove the entire disclosure in the intervening reference from being prior art.” In the instant case, Applicant cites Sterling et al. and states that Sterling et al. teaches reducing retinal inflammation, Al astrocyte activation, and loss of retinal ganglion cells secondary to elevated intraocular pressure (eIOP) in a subject, by administering the GLP-1 receptor agonist NLY01. Sterling et al. does not disclose liraglutide, dulaglutide, or semaglutide taught by Sinclair. If Applicant continues to invoke the prior art exception under AIA 35 U.S.C. 102(b)(2)(B) using Sterling et al., these facts should be addressed and considered. The rejection is maintained. Claim Rejections - 35 USC § 103 - withdrawn The rejection of claims 1-2, 4-6, 13, 15-18, 20-22, 29, 33-34, 36-38, 45 and 51-53 under 35 U.S.C. 103 as being unpatentable over US 2016/0000882 in view of Bell (“The Different Types of Glaucoma Explained” [online]. Posted October 3, 2019 [retrieved May 23, 2024]. Retrieved from the internet: <https://www.eyecenteroftexas.com/2019/10/different-types-of-glaucoma/>), Conlon et al. (“Glaucoma treatment trends: a review,” Can J Ophthalmol, Vol. 52, No. 1, February 2017, pp. 114-124) and Gonçalves et al. (“Protective Effect of a GLP-1 Analog on Ischemia-Reperfusion Induced Blood-Retinal Barrier Breakdown and Inflammation,” Invest Ophthalmol Vis Sci. 2016;57:2584–2592) is withdrawn in view of the arguments filed December 17, 2025. Claim Rejections - 35 USC § 103 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 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. Goncalves Claims 1-2, 17-18, 33-34, and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over Gonçalves et al. (“Protective Effect of a GLP-1 Analog on Ischemia-Reperfusion Induced Blood-Retinal Barrier Breakdown and Inflammation,” Invest Ophthalmol Vis Sci. 2016;57:2584–2592) in view of Hernández et al. (“Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes,” Diabetes 2016;65:172–187). Gonçalves et al. teach a method of administering the GLP-1 receptor agonist exendin-4 prior to and following by a period of increased intraocular pressure. The period of increased IOP followed by reperfusion induced ischemia-reperfusion injury (p. 2585, col. 1). Gonçalves et al. teach that exendin-4 reduced the BRB permeability induced by IR injury, which was associated with suppression of inflammatory gene expression (p. 2586, col. 2). Gonçalves et al. teach that exendin-4 also reduced the inflammatory response to LPS and inhibited NF-kB activation (p. 2588, col. 2). Gonçalves et al. suggest that exendin-4 can prevent IR injury-induced BRB breakdown and inflammation through inhibition of inflammatory cytokine production by activated microglia and may provide a novel option for therapeutic intervention in diseases involving retinal inflammation (p. 2591, col 1). Gonçalves et al. do not teach administration of liraglutide as the GLP-1 agonist. Hernandez et al. teach that GLP-1R is abundantly expressed in the human retina (p. 175). Hernandez et al. teach that systemic administration of the GLP-1R agonist liraglutide prevents retinal neurodegeneration (glial activation, neural apoptosis, and electroretinographical abnormalities) due to a significant reduction of extracellular glutamate and an increase of prosurvival signaling pathways (p. 175-176). Hernandez et al. teach that topical administration of GLP-1R agonists liraglutide, lixisenatide, and exenatide also has a neuroprotective effect without any reduction in blood glucose levels (p. 176-177). Hernandez et al. teach that GLP-1R activation itself prevents retinal neurodegeneration (p. 185). It would have been obvious to substitute liraglutide taught by Hernandez et al. in the method taught by Gonçalves et al. because these are art-recognized equivalents, as evidenced by the fact that they are each known GLP-1 agonists. Furthermore, Hernandez et al. demonstrates that liraglutide has neuroprotective effects in the retina upon systemic and topical administration. The resulting method would comprise administering liraglutide to reduce retinal inflammation in a subject with elevated IOP, satisfying all of the limitations of claims 1-2. With respect to claims 17-18 and 33-34, effects on production of IL-l, TNF-, and Clq by CD11b+ CD11c+ and CD11b+ CD11c- cells, and transformation of astrocytes to would occur as a result of administering the same active agent, to the same patients, in the same manner as in the instant claims. With respect to claims 51-53, both references teach administration by injection. Response to Arguments Applicant's arguments filed December 17, 2026 have been fully considered but they are not persuasive. In response to applicant's argument that Gonçalves et al. and Hernandez et al. do not motivate a skilled artisan to reduce retinal inflammation and neuron death secondary to ocular hypertension in a subject with elevated IOP, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Gonçalves et al. teach a method of administering the GLP-1 receptor agonist exendin-4 prior to and following a period of elevated IOP (p. 2585, col. 1). Hernandez et al. teach the GLP-1 receptor agonist liraglutide (p. 176-177). It would have been obvious to substitute one GLP-1 receptor agonist for another because one of ordinary skill in the art would expect compounds of the same class to function the same way. In doing so, one of ordinary skill in the art would practice a method of administering the GLP-1 receptor agonist liraglutide prior to and following a period of elevated IOP. The effect of this action on retinal inflammation and neuron death secondary to ocular hypertension would occur as a result of practicing the obvious method of administering the same drug, to the same subject, and in the same manner as required by the claims. The record does not include any evidence that the claimed method has properties that are unexpected in view of the prior art. For these reasons, the rejection is maintained. Conclusion No claims are allowed. THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm. 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, Lianko G Garyu can be reached on (571) 270-7367. 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. /CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
Read full office action

Prosecution Timeline

Oct 18, 2021
Application Filed
Jan 11, 2023
Non-Final Rejection — §102, §103
Jul 13, 2023
Response Filed
Sep 21, 2023
Final Rejection — §102, §103
Mar 26, 2024
Request for Continued Examination
Mar 29, 2024
Response after Non-Final Action
May 23, 2024
Non-Final Rejection — §102, §103
Nov 21, 2024
Response Filed
Dec 06, 2024
Final Rejection — §102, §103
Apr 10, 2025
Request for Continued Examination
Apr 11, 2025
Response after Non-Final Action
Apr 21, 2025
Response Filed
Jun 16, 2025
Non-Final Rejection — §102, §103
Dec 17, 2025
Response Filed
Feb 20, 2026
Final Rejection — §102, §103 (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

7-8
Expected OA Rounds
63%
Grant Probability
96%
With Interview (+32.9%)
2y 10m
Median Time to Grant
High
PTA Risk
Based on 1018 resolved cases by this examiner. Grant probability derived from career allow rate.

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