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
Applicant’s amendment filed 08/26/2025 is acknowledged. Claim 1 is amended. According to Applicant’s Remarks filed 08/26/2025, claim 1 has been amended and claim 12 has been canceled, however, in the instant claim set filed 08/26/2025, claim 12 has not been canceled. Claims 1-16 are under examination.
Objections Withdrawn
Specification
The objection to the specification because the title of the invention is not descriptive is withdrawn in response to Applicant’s submission of an amended title as suggested by examiner: NEURAL REGENERATION WITH SYNTHETIC NORRIN TRUNCATE ADMINISTRATION.
Claim Objections
The objection to claim 1 for minor informalities is withdrawn in response to Applicant’s amendment to claim 1 fixing the grammatical/typographical error.
The amendment to claim 1 to define the acronym LGR4 as “leucine-rich repeat containing G-protein coupled receptor 4 (see p. 31, paragraph [0106] of the instant specification) is acknowledged. The examiner presumes that LGR5 and LGR6 have not been defined in order to avoid adding new matter.
Rejections Maintained
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
The rejection of claims 1-3, 5-12, 15 and 16 under 35 U.S.C. 103 as being unpatentable over Trese et al. (US 2016/0355559) in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15) is maintained for reasons of record and the following. As noted in the previous Office action mailed 05/20/2025, Trese et al. teach administering via intraocular injection to a subject an effective amount of norrin polypeptide comprising SEQ ID NO: 2 to the retinal vessel cells or the choroidal vessel cells or a fragment of SEQ ID. NO. 1 that binds a frizzled-4 receptor of the retinal vessel cells, wherein said subject is a human, a cow, a horse, a sheep, a pig, a goat, a chicken, a cat, a dog, a mouse, a guinea pig, a hamster, a rabbit, or a rat. The alignment between the norrin mutant taught by Trese and colleagues and instant SEQ ID NO: 2 is as follows:
Query Match 100.0%; Score 597; Length 109;
Best Local Similarity 100.0%;
Matches 109; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KTDSSFIMDSDPRRCMRHHYVDSISHPLYKCSSKMVLLARCEGHCSQASRSEPLVSFSTV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 KTDSSFIMDSDPRRCMRHHYVDSISHPLYKCSSKMVLLARCEGHCSQASRSEPLVSFSTV 60
Qy 61 LKQPFRSSCHCCRPQTSKLKALRLRCSGGMRLTATYRYILSCHCEECNS 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LKQPFRSSCHCCRPQTSKLKALRLRCSGGMRLTATYRYILSCHCEECNS 109
In addition, at paragraph [0052], Trese et al. teach that the encompassed mutations include an amino acid substitution of R→E at residue 64 relative to SEQ ID NO: 1, which is the same as instant SEQ ID NO: 3, or of E→A at residue 130 relative to SEQ ID NO: 1, which is the same as instant SEQ ID NO: 14, for example. Trese et al. teach tightening inter-cellular junctions in retinal vessel cells or choroidal vessel cells to treat retinal edema, and do not disclose the effects on expression of LGR4, LGR5 or LGR6 and activating a Wnt signaling pathway to reverse clinical conditions associated with nerve degradation or disease, as recited in amended claim 1.
The instant specification discloses “reversing clinical conditions associated with
the nerve degradation or disease” and “specific clinical conditions reversed” include “hearing loss, tinnitus, and a host of neurotrophic retinopathies, diabetes, [and] Norrie disease” (see paragraph [0032]). The specification contemplates the invention is relevant to “the treatment of many eye and ear diseases characterized by anomalous vasculature and anomalous nerve development…illustratively including FEVR” (see paragraph [0123]). Similarly, Trese et al. contemplate a patient population with “familial exudative vitreoretinopathy (FEVR) and related vitreoretinopathies”. Since Trese et al. teach administration of the same agent in situs, i.e., to the eye, to treat an eye disease, they encompass treatment of the same patient population with the same agent.
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that the methods of Trese et al. would reverse clinical conditions associated with nerve degradation and disease because Leopold et al. teach that norrin itself is protective against retinal degeneration (see abstract; p. 2, 1st paragraph). The effects on expression of LGR4, LGR5 and LGR6 or activating a Wnt signaling pathway to effect this reversal would have been inherent to the combined prior art teachings because they teach administering the same norrin truncate to the same patient population as recited in the instant claims. The same clinically significant improvements as recited in claim 1 must occur as a result of administering the norrin truncate taught in Trese et al. to the retina of the patient population being treated for eye diseases. The recitation of the effects of the norrin truncates on the patient population are part of to the understandings and expectations disclosed in the prior art.
The method of treating retinal disease and the structure of the norrin truncate for carrying out that treatment was part of the disclosure of the combined prior art teachings, so the effects upon the body of the patients are inherent. Further, for the record, the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983) and MPEP 2112. Furthermore, the person of ordinary skill in the art could have reasonably expected success because the prior art taught that norrin was protective of nerves in the retina; one having ordinary skill in the art, upon reading the claims of the reference patent, would understand that the same effects as recited in the instant claims would occur as a result of the methods recited in the reference claims.
Thus, the claims do not contribute anything non-obvious over the prior art.
Response to Arguments
At pages 7-8, Applicant argues that in the absence of an explicit teaching or suggestion of all claim limitations, a prima facie case of obviousness is not met, citing In re Royka. Specifically, Applicant argues that Trese et al. is silent with regard to nerve regeneration or reversing clinical conditions associated with nerve degradation or disease, but rather teaches limiting degradation of beta-catenin and tightening inter-cellular junctions in retinal or choroidal vessel cells. Finally, Applicant argues that Leopold et al. teaches Wnt activation of the catenin signaling pathway is implicated in retinal ganglion cell regeneration only after acute injury, and not clinical conditions associated with nerve degradation or disease.
These arguments have been fully considered, but are not found persuasive. To clarify the record, the rejection was made under 35 USC 103, not 102, as stated by Applicant at p. 7, 3rd paragraph of the Remarks. The case law cited by Applicant does not appear in the MPEP, and a Google search indicates that with the exception of two claims, all of the claims in Royka were rejected as anticipated under 35 USC 102. The instant claims were rejected under 35 USC 103 as being obvious over Trese et al. in view of Leopold.
Trese et al. teach treating a patient population suffering from eye disease comprising administering via intraocular injection an effective amount of norrin polypeptide (see teachings outlined above). As noted by Applicant, Trese et al. discloses norrin binds to a frizzled-4 receptor and limits β-catenin degradation. However, it is not persuasive that Leopold teaches Wnt activation of the catenin signaling pathway is implicated in retinal ganglion cell regeneration only after acute injury. While Leopold et al. teach that Wnt/β-catenin signaling is activated during acute eye injury (see p. 1, 2nd paragraph), they also conclude that both norrin and Wnt/β-catenin signaling are involved in chronic eye disease, noting that norrin protects retinal ganglion cells and their axons from chronic damage via the Wnt/β-catenin pathway and its downstream neuroprotective effects (see p. 7, last paragraph). See also p. 11, under “Conclusions”:
[W]e identified important components of a protective signaling network that is powerful to attenuate optic nerve degeneration in chronic glaucoma. Norrin, canonical Wnt/β-catenin signaling, IGF-1 and enhanced activity of PI3K-Akt signaling are involved, each of which might be a promising target to further develop therapeutic strategies to prevent glaucomatous damage in human patients.
Thus, the teachings of Leopold et al. provide a nexus between the mechanism of action proposed by Trese et al. and activating Wnt/β-catenin signaling. The broadest reasonable interpretation of clinical conditions associated with nerve degradation or disease encompasses both acute and chronic conditions. Many chronic conditions, for example, diabetes, can result in acute injuries and complications; there is no bright line distinction. Moreover, there is nothing in the claims that precludes treatment of acute injury. Applicant is arguing limitations not present in the claims.
The rejection of claim 4 under 35 U.S.C. 103 as being unpatentable over Trese et al. (US 2016/0355559) in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15) as applied to claims 1-3, 5-12, 15 and 16 above, and further in view of Renner et al. (Front. Cell. Neurosci. (2017) 11: 254) is maintained for reasons of record and the following.
Response to Arguments
While the heading at p. 9 correctly states the remarks are directed to the rejection under 35 U.S.C. § 103 over Trese et al., Leopold et al., and Renner et al., the arguments are made with respect to a rejection under 35 USC 102 of claims 1, 3, 5 and 11 as being anticipated by Wu et al. A careful review of the Office action mailed 05/20/2025 did not reveal any rejections under 35 USC 102 over Wu et al. Applicant argues Wu et al. omits LRP5 and an unexpected result of treatment effectiveness. Applicant argues further that claim 1 is now in “closed form”, thereby excluding the teaching of additional therapeutics.
These arguments have been fully considered, but are not found persuasive. First, the claims do not recite LRP5, nor is any rejection made over Wu and colleagues. Further, claim 1 recites a method “comprising”, and is therefore not in closed form. The rejection is maintained based upon the record and the aforementioned Response to Arguments regarding claims 1-3, 5-12, 15 and 16 over Trese et al. in view of Leopold et al.
The rejection of claims 13 and 14 under 35 U.S.C. 103 as being unpatentable over Trese et al. (US 2016/0355559) in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15) as applied to claims 1-3, 5-12, 15 and 16 above, and further in view of Zhang et al. (WO 2018/140821) is maintained for reasons of record and the following. Specifically, Applicant’s Remarks at p. 10 address a rejection of claims 1, 3, 5, 11 and 12 over Wu et al., Drenser and Patel et al., however, no such rejection was made in the Office action mailed 05/20/2025. The rejection is maintained based upon the record and the aforementioned Response to Arguments regarding claims 1-3, 5-12, 15 and 16 over Trese et al. in view of Leopold et al.
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. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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); 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
The following rejections on the ground of nonstatutory double patenting are maintained for reasons of record and the following.
The rejection of claims 1-16 as being unpatentable over claims 1-13 of U.S. Patent No. 10,703,787 in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15), Renner et al. (Front. Cell. Neurosci. (2017) 11: 254) and Zhang et al. (WO 2018/140821).
The rejection of claims 1-16 as being unpatentable over claims 1-13 of U.S. Patent No. 10,202,429 in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15), Renner et al. (Front. Cell. Neurosci. (2017) 11: 254) and Zhang et al. (WO 2018/140821).
The rejection of claims 1-3, 7-9, 11 and 13-16 as being unpatentable over claims 1-9 of U.S. Patent No. 10,669,321 in view of in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15) and Zhang et al. (WO 2018/140821).
The provisional rejection of claims 1-16 as being unpatentable over claims 1-8, 11-14, 16-20 and 24-26 of copending Application No. 17/910,467 (mistyped as 17/710,467 in the Office action mailed 05/20/2025) in view of in view of Leopold et al. (Scientific Reports, 2017; 7: 14274; pages 1-15), Renner et al. (Front. Cell. Neurosci. (2017) 11: 254) and Zhang et al. (WO 2018/140821).
Response to Arguments
Applicant argues at p. 11 that “the double patenting rejections are overcome in view of the above amendments and remarks” with regard to 35 USC 103 and that “[i]n the event that the double patenting rejections are maintained, Applicant is willing to provide a terminal disclaimer in order to progress prosecution.”
This argument has been fully considered but is not found persuasive. The rejections are maintained based upon reasons of record. See the aforementioned “Response to Arguments” regarding the rejections under 35 USC 103, hereby incorporated, for the explanation as to why the rejections are maintained. Furthermore, Applicant’s apparent request for deferral of this issue is not proper; an argument after the claims have been found otherwise allowable that obviousness type double patenting does not exist will not be considered timely. Accordingly, the rejections are maintained.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675