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 I, including claims 5-7, 23-25, 34-38, and 42, in the reply filed on 12/03/2024, is acknowledged. Election was made without traverse in the reply filed on 12/03/2024.
Claim Status
Claims 5-10, 15-18, 23-25, 34-38, and 41-47 are currently pending. Claims 8-10, 15-18, 24, 37, 38, and 41 are withdrawn. Claim 42 has been cancelled. Claims 5-7, 23, 25, and 34-36 are under current examination.
Specification
The objection to the specification has been withdrawn in light of the amendment submitted on 6/18/25.
Claim Objections
The objection to claim 23 has been withdrawn in light of the amendment submitted on 6/18/25.
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.
The rejection of claims 5 and 42 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
Claim Rejections - 35 USC § 103 Maintained in Modified Form
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.
Claims 5-7, 23, 25, and 34-36 are rejected under 35 U.S.C. 103 as being unpatentable over Yoo et al. (WO 2019067540 A1; pub. date 04/04/2019; ISR of record 09/30/2021) in view of Matteoli et al. (Infrared Physics & Technology 76 (2016) 402-407).
Regarding claim 5, Yoo teaches a method of treating a human subject diagnosed with neovascular age-related macular degeneration ("nAMD"), also known as "wet" age-related macular degeneration ("W AMD" or "wet AMD") comprising administering to the
suprachoroidal space in the eye of said human subject a composition comprising an expression vector encoding an anti-human vascular endothelial growth factor (h VEGF) antibody (page 68, set 2, #1). Yoo teaches AAV2 inverted terminal repeats that flank the expression cassette; (2) Control elements, which include a) the CB7 promoter, comprising the CMV enhancer/chicken β-actin promoter, b) a chicken β-actin intron and c) a rabbit β-globin poly A signal; and (3) nucleic acid sequences coding for the heavy and light chains of anti-VEGF antigen-binding fragment, separated by a self-cleaving furin (F)/F2A linker, ensuring expression of equal amounts of the heavy and the light chain polypeptides (page 99, paragraph 00174), thereby teaching expression of the anti-hVEGF antigen-binding fragment as claimed. Additionally, the sequences disclosed in Yoo (WO 2019067540 A1) demonstrate a 100% similarity to “a nucleotide sequence encoding: an IL-2 signal peptide; a heavy chain of the anti-hVEGF antigen-binding fragment comprising the amino acid sequence of SEQ ID NO: 2 and a second IL-2 signal peptide a light chain of the anti-hVEGF antigen-binding fragment comprising the amino acid sequence of SEQ ID NO: 1” as required for claim 5 (sequence alignments below).
However, Yoo does not teach monitoring the post ocular injection thermal profile of the composition in the eye using an infrared thermal camera.
Matteoli teaches eyes treated with intravitreal anti-VEGF drugs prior to thermographic examination (page 403, Materials and Methods, 2.1 Subjects). Matteoli teaches the use of infrared thermography using an FLIR A320 camera (page 402, Abstract). Matteoli teaches a thermographic profile characterized by higher temperatures at the extremities (P1 and P5), and a lower temperature in the central area (P3) was found in all subjects (both pathological and controls) (page 404, Results, and Fig. 1 & 2).
These disclosures teach administering an expression vector to the suprachoroidal space in the eye and infrared thermography following post ocular injection.
It would have been obvious to an artisan of ordinary skill in the art, before the effective filing date of the claimed invention to modify the method of suprachoroidal administration disclosed in Yoo by incorporating the thermographic examination techniques taught by Matteoli. An artisan of ordinary skill in the art would have been motivated to combine these references because Yoo teaches administering an expression vector to the suprachoroidal space of a human eye with neovascular age-related macular degeneration (nAMD), while Matteoli demonstrates the evaluation of the thermographic profile may be a reliable tool to appreciate large vascular changes (page 406, Discussion) and infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the evaluation of patients with AMD (page 406, Conclusions). The ordinary artisan would reasonably expect success because Matteoli discloses infrared thermography could be used to detect possible choroidal atrophic changes consequent to repeated anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection and may be a helpful, non-invasive and not time-consuming method to be used in the evaluation of patients with AMD (page 406, Discussion & Conclusion).
Regarding claim 6, Yoo teaches administering is by injecting the expression vector into the suprachoroidal space using a drug delivery service (page 193, claim 2).
Regarding claim 7, Yoo teaches the suprachoroidal drug delivery service is a microinjector (page 193, claim 3).
Regarding claim 23, Yoo teaches the anti-h VEGF antibody comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 17-19 or SEQ ID NOs: 20, 18, and 21 (page 194, claim 23). The CDR sequences recited in claim 23 are part of SEQ ID NOs: 1 and 2 recited in claim 5, as demonstrated by sequence analysis showing 100% match.
Regarding claim 25, Yoo teaches methods of treating a human subject diagnosed with neovascular age-related macular degeneration (nAMD) (page 4, paragraph 0010).
Regarding claim 34, Yoo teaches delivering to the retina of said human subject a therapeutically effective amount of anti-hVEGF antigen-binding fragment by administering via the suprachoroidal space (page 54, lines 7-11, Illustrative Embodiments 3.1, #2)
Regarding claim 35, Yoo teaches a therapeutically effective amount of anti-hVEGF antigen-binding fragment produced by human retinal cells by administering via the suprachoroidal space in the eye of said human subject. (page 54, lines 7-8, Illustrative Embodiments 3.1, #2).
Regarding claim 36, Yoo teaches a therapeutically effective amount of anti-h VEGF antigen-binding fragment produced by retinal pigment epithelial cells in the external limiting membrane (page 54, lines 19-24, Illustrative Embodiments 3.1, #4).
Regarding claim 42, Matteoli teaches the thermocamera used was the FLIR 320A (page 404, 2.2 Thermographic procedure).
Therefore, the combined prior art references render the claims obvious.
Heavy Chain SEQ ID NO: 2 (claim 5)
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Light Chain SEQ ID NO: 1 (claim 5)
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Response to Arguments
Applicant argues that while a passage of Matteoli at page 403 refers to “eyes treated with intravitreal anti-VEGF drugs prior to thermographic examination”, there is not disclosure, teaching or suggestion in the Matteoli of the feature “…after the administering, monitoring a thermal profile of the composition in the eye using an infrared thermal camera as recited in claim 5. See page 12 of the response submitted on 6/18/25. Applicant goes on to assert that Matteoli describes a study investigating ocular surface temperature (OST) in eyes affected by AMD using infrared thermography. Applicant continues that the purpose of Matteoli’s study was to compare OST between AMD and healthy eyes, not to monitor injections. See page 12 of Applicant’s response. Further, Applicant argues that there is no disclosure, teaching or suggestion in Matteoli of monitoring a thermal profile of an administered compound. See the top of page 13 of Applicant’s response.
In response, these arguments are not persuasive. It is appreciated that applicant is attempting to distinguish monitoring the thermal profile of the administered composition from monitoring OST, which is a thermal profile, after administration of anti-VEGF drgus. It is not apparent though how these can be separate, particularly since the specification has not provided a definition for “monitoring a thermal profile” and “thermal profile of the composition”. Figure 6 shows use of an infrared camera to monitor thermal profile post suprachoroidal injection but does not explain if the thermal profile is of the eye or composition. Paragraph [0042] discusses monitoring temperature of the surface of the eye using an infrared camera; paragraph [0175] discusses how an infrared thermal camera can be used to detect changes in the thermal profile of the ocular surface after administering a solution which is cooler than body temperature that allows for visualization of the spread of the solution; paragraph [0176] discusses that thermal cameras can detect small changes in temperature via any method of administration to the eye; paragraph [0178] discusses that an iron filer is used with the infrared thermal camera to detect changes in the thermal profile of the ocular surface; paragraph [0179] discusses how the thermal profile for different routes of administration [to the eye] can be different; Example 21, paragraph [0458] discusses how an infrared thermal camera could be characterize post ocular injection thermal profiles in pigs by characterizing the spread injected solution by temperature gradients, which appears to be done by detecting changes in the thermal profile of the ocular surface as discussed in paragraph [0175]; and Example 22, paragraph [0461] extrapolates Example 21 to human subjects. Given all the recitations and examples provided by the specification directed to monitoring thermal profiles of the ocular surface it would be reasonable to interpret the claim language, “monitoring the thermal profile of the composition” as including monitoring the thermal profile of the ocular surface after administration [of anti-VEGF drugs] as they do not appear to be mutually exclusive. This interpretation would embrace monitoring the ocular thermal profile post-injection of anti-VEGF drugs as discussed by Matteoli. See the rejection above.
Applicant argues Matteoli only measured OSTs at superficial points such as the cornea and surrounding areas. A composition administered to deeper ocular areas such as the suprachoroidal space may not have been reasonably expected to produce a detectable thermal profile.
In response, the examiner asserts that Matteoli sought to investigate the effect of intravitreal anti-VEGF drug injection on the OST. See page 404, right column, 5 paragraph in the results section. Additionally, Yoo taught administration of their treatment to the suprachoroidal space. See the at the beginning of the 103 rejection above. Matteoli provides motivation for measuring OST post anti-VEGF injection by suggesting that thermography could be used to detect possible choroidal atrophic changes in AMD patients (see page 406, first column, in the first full paragraph) and more general motivation by stating “infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the evaluation of patients with AMD”. Since both Yoo and Matteoli relate to treating and evaluating AMD in patients receiving anti-VEGF treatments there is ample motivation for combining the references.
It is noted that applicant has not provided any arguments towards the Yoo reference. Accordingly, the rejection is maintained for the reasons of record.
Conclusion
No claim is 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.
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/PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632