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 .
Priority
This Application is a 371 of PCT/EP2021/057126, filed Mar. 19, 2021, and claims foreign priority to EP20164345.9, filed Mar. 19, 2020.
Claim Status
Claims 1 and 5-20 are currently pending and subject to examination.
Claim Rejections- Overcome by Amendment
The rejection of claims 2-4 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn.
The rejection of claims 1-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
The above rejections were overcome by Applicant’s amendment to the claims.
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.
The rejection of claim(s) 1 and 5-20 under 35 U.S.C. 103 as being unpatentable over Maltas et al. (US 9,682,967 B2, published June 20, 2017) in view of Peterson et al. (US 8,377,701 B2, published Feb. 19, 2013) is maintained.
The rejection of claim(s) 1 and 5-20 under 35 U.S.C. 103 as being unpatentable over Maltas et al. (US 9,682,967 B2, published June 20, 2017) in view of Peterson et al. (US 8,377,701 B2, published Feb. 19, 2013) and Schroder et al. (Bioorganic & Medicinal Chemistry Letters, Vol. 24, Issue 1, 1 Jan. 2014, p. 177-180) (of record IDS 12/16/2022 Cite no. 4) is maintained.
Response to Arguments
The Applicant argues that there is no motivation to combine Maltas with Peterson and no reasonable expectation of success because the compounds in Peterson are different from those of Maltas and there is no data or evidence in Peterson that sortilin inhibitors can treat diabetic retinopathy or any disease. (Remarks, p. 8-9). Applicant's arguments filed Sept. 24, 2025 have been fully considered but they are not persuasive.
First, in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385 (2007), the Supreme court rejected an explicit teaching-suggestion-motivation test for obviousness. There are many rationales to support a conclusion of obviousness and “Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention” is only one such rationale (MPEP § 2143.I).
Moreover, ‘"It's enough … to show that there was a known problem … in the art, that [another reference] … helped address that issue, and that combining the teachings of [the two references] wasn't beyond the skill of an ordinary artisan. Nothing more is required to show a motivation to combine under KSR." See Intel Corp. v. PACT XPP Schweiz AG, 61 F.4th 1373, 1380-81, 2023 USPQ2d 297 (Fed. Cir. 2023) (finding that both prior art references "address the same problem and that [the secondary reference’s] cache was a known way to address that problem is precisely the reason that there's a motivation to combine under KSR and our precedent.")” (MPEP § 2143.I.C). Here, there is an identified problem in the art, diabetic retinopathy. Peterson helped address this problem by providing sortilin inhibitors and combining Peterson and Maltas was well within the level of ordinary skill because both references are on the subject of sortilin inhibitors for the treatment of retinal degeneration.
One of ordinary skill in the art would have a reasonable expectation of success to apply the sortilin inhibitors of Maltas for the treatment of diabetic retinopathy because Maltas specifically teaches that these compounds treat retinal degeneration, there are only a finite number of causes of retinal degeneration, and Peterson explicitly teaches that sortilin inhibitors are useful for retinal degeneration caused by diabetic retinopathy. It is not persuasive that the structural differences in the sortilin inhibitors of Maltas and Peterson would undermine the reasonable expectation of success because both references are intended to accomplish the same function: inhibition of sortilin for the treatment of retinal degeneration.
The Applicant argues that diabetic retinopathy is speculative because it is mentioned among a long list of possible diseases in Peterson (Remarks, p. 9). These arguments were fully considered but are not persuasive. Maltas teaches the identical compounds for the treatment of retinal degeneration. It is known that retinal degeneration is caused by a finite number of conditions, one of which is diabetic retinopathy. One of ordinary skill in the art could apply the compounds of Maltas with a reasonable expectation of success because Peterson teaches diabetic retinopathy as the cause of retinal degeneration relevant for treatment with sortilin inhibitors. In the context of Maltas, the other conditions referenced by Peterson are irrelevant.
Reiterated Rejection
Claim(s) 1 and 5-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maltas et al. (US 9,682,967 B2, published June 20, 2017) in view of Peterson et al. (US 8,377,701 B2, published Feb. 19, 2013).
Claim 1 is directed towards a method of prevention or treatment of diabetic retinopathy comprising administration of a therapeutic amount of a sortilin antagonist to a subject in need thereof, wherein the sortilin antagonist is a compound of formula (I):
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. One of ordinary skill in the art would have a reasonable expectation of success to treat diabetic retinopathy with sortilin inhibitors of formula (I) because Maltas teaches sortilin inhibitors of formula (I) for the treatment of retinal degeneration and Peterson teaches that sortilin inhibitors are useful for the treatment of neuronal diseases such as diabetic retinopathy.
Maltas teaches sortilin antagonists of formula A with overlapping scope to instant formula (I):
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(Maltas, Specification, col. 4, lines 10-25). Maltas teaches the same sortilin antagonists of formula (I) as in the instant invention, for example:
Instant Specification
Maltas Specification
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Ex. 1, p. 22.
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Ex. 2, col. 47.
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Ex. 5, p. 23.
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Ex. 4, col. 48.
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Ex. 6, p. 23.
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Ex. 3, col. 48.
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Ex. 8, p. 23.
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Ex. 1, col. 57.
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Ex. 14, p. 24.
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Ex. 5, col. 49.
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Ex. 21, p. 26.
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Ex. 21, col. 56.
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Ex. 22, p. 26.
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Ex. 22, col. 56.
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Ex. 27, p. 26.
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Ex. 34, col. 62.
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Ex. 28, p. 27.
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Ex. 37, col. 63.
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Ex. 30, p. 27.
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Ex. 46, col. 66.
Maltas teaches that the above sortilin inhibitors may be used in a method for treatment of retinal degeneration (Maltas, Specification, column 13, line 40). While Maltas does not teach that the retinal degeneration is due to diabetic retinopathy, one of ordinary skill in the art would have a reasonable expectation of success to apply the sortilin inhibitor to diabetic retinopathy because Peterson teaches sortilin inhibitors for damage involving the retina including diabetic retinopathy:
In one aspect the present invention relates to a medicament comprising an inhibitor of Sortilin and/or of Sortilin:proNGF:p75NTR induced apoptosis.
In one embodiment of the present invention the at least one ligand as identified by the methods described herein above is used for the manufacture of a medicament, wherein said medicament is for the treatment, and prevention or treatment and prevention of and/or protection against a disease, disorder, or damage of the nervous system in an individual.
Peterson, Specification, col. 37, lines 14-22;
In one embodiment of the present invention the nervous system disorder, disease, or damage involves the retina, photoreceptors, and associated nerves.
In one embodiment of the present invention the nervous system disorder, disease, or damage involving the retina, photoreceptors, and associated nerves is selected from the group consisting of retinitis pigmentosa, macular degeneration, glaucoma, and diabetic retinopathy.
Peterson, Specification, col. 38, lines 14-21 (emphasis added).
Therefore, claim 1 was prima facie obvious at the time of filing.
Claim 2 is directed towards the method of claim 1, wherein:
the sortilin antagonist disrupts an interaction between a sortilin or sortilin- related molecule and a pro-neurotrophin molecule; or
the sortilin antagonist disrupts an interaction between a sortilin or sortilin- related molecule and a p75NTR molecule.
Claim 3 is directed towards the method of claim 2, wherein the sortilin is mature sortilin or wherein the isortilin related molecule is SorCS2. Claim 4 is directed towards the method of claim 1, wherein the sortilin antagonist is a sortilin inhibitor. These are all inherent properties of the compound of formula (I) which are de facto present in the disclosure of Maltas. Therefore, claims 2-4 were prima facie obvious at the time of filing.
Claim 5 is directed towards the method of claim 1, wherein the sotrilin antagonist has a molecular weight of less than 2000 Da, preferably less than 1000 Da. The compounds shown above taught by Maltas all have molecular weights of less than 1000 Da. Therefore, claim 5 was prima facie obvious at the time of filing.
Claim 6 is directed towards the method of claim 1, wherein Y is -NR5- preferably -NH-. In the compounds taught by Maltas, Y is -NH-. Therefore, claim 6 was prima facie obvious at the time of filing.
Claim 7 is directed towards the method of claim 1, wherein A and D are H. In the compounds taught by Maltas, A and D are H. Therefore, claim 7 was prima facie obvious at the time of filing.
Claim 8 is directed towards the method of claim 1, wherein B and C are independently selected from H, halo, CF3, NO2, C1-3 alkyl, and C4 alkyl. Maltas teaches compounds of claim 1 wherein B and C are independently H, halo, CF3, or C1-3 alkyl. Therefore, claim 8 was prima facie obvious at the time of filing.
Claim 9 is directed towards the method of claim 1, wherein C is H. In the compounds taught by Maltas, C is H. Therefore, claim 9 was prima facie obvious at the time of filing.
Claim 10 is directed towards the method of claim 1, wherein B is halo or CF3, preferably Br or CF3. Maltas teaches compounds wherein B is Br or CF3. Therefore, claim 10 was prima facie obvious at the time of filing.
Claim 11 is directed towards the method of claim 1, wherein Z is substituted or unsubstituted C6-10 aryl or C1-9 heteroaryl, preferably substituted or unsubstituted phenyl or pyrimidinyl. Maltas teaches compounds wherein Z is substituted or unsubstituted pyridinyl or pyrimidinyl. Therefore, claim 11 was prima facie obvious at the time of filing.
Claim 12 is directed towards the method of claim 1, wherein the C6-10 aryl or C1-9 heteroaryl are unsubstituted or substituted with one or more substituents selected from the group consititing of Cl, -OMe-, and Me and/or wherein an alkylene group is attached to two adjacent atoms of the aryl or heteroaryl group to form a 5- or 6-membered partially saturated or saturated ring. Maltas teaches that the heteroaryl is unsubstituted or may be substituted with Cl, -OMe-, or Me and a saturated dual ring structure as in claim 12 (e.g. Ex. 46, col. 66). Therefore, claim 12 was prima facie obvious at the time of filing.
Claim 13 is directed towards the specific species of sortilin antagonist of formula (I) as in claim 1. The rejection of claim 1 is incorporated herein by reference. Therefore, claim 13 was prima facie obvious at the time of filing.
Claim 14 is directed towards a method of treatment or prevention of diabetic retinopathy comprising administering to a subject in need therefore a pharmaceutical formulation comprising the sortilin antagonist of claim 1, and or one more pharmaceutically acceptable carriers or excipients. Maltas teaches that “The compounds of the present invention may be administered alone as a pure compound or in combination with pharmaceutically acceptable carriers or excipients, in either single or multiple doses. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents.” (Maltas, Specification, col. 13-14). Therefore, claim 14 was prima facie obvious at the time of filing.
Claim 15 is directed towards the method of claim 14, wherein the formulation is an ophthalmic formulation. Maltas teaches that:
The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) route. It will be appreciated that the preferred route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen.
Maltas, Specification, lines 8-18.
Maltas also expressly teaches that the compounds of the instant invention may be used for disorders of the eye including retinal degeneration and light-induced photoreceptor degeneration (Maltas, Specification, col. 13, lines 40-41).
While Maltas does not exemplify an ophthalmic formulation, one of ordinary skill in the art would have a reasonable expectation of success to formulate the compound of claim 1 in an ophthalmic formulation because Maltas teaches topical/ transmucosal routes as well as aqueous solutions (Maltas, Specification, col. 14, line 26) and ointments (Maltas, Specification, col. 14, line 31) and Peterson teaches that sortilin inhibitors can be administered through any mucosal membrane including the eye (Peterson, col. 38, line 56). Therefore, claim 15 was prima facie obvious at the time of filing.
Claims 16-20 are newly added, but read on the compounds mentioned in the rejection of claim 1. As such, these claims are rejected on the same grounds as claim 1 and were prima facie obvious at the time of filing.
Claim(s) 1 and 5-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maltas et al. (US 9,682,967 B2, published June 20, 2017) in view of Peterson et al. (US 8,377,701 B2, published Feb. 19, 2013) and Schroder et al. (Bioorganic & Medicinal Chemistry Letters, Vol. 24, Issue 1, 1 Jan. 2014, p. 177-180) (of record IDS 12/16/2022 Cite no. 4).
The rejection of claims 1 and 5-20 under 35 U.S.C. 103 as being unpatentable over Maltas in view of Peterson is incorporated here by reference.
Schroder is cited herein to show that the compounds of the instant invention are commonly known as sortilin inhibitors. While Maltas does not teach sortilin inhibitors wherein Z is alkyl or phenyl, sortilin inhibitors of formula (I) wherein Z is alkyl or phenyl are known in the art. For example, Schroder teaches the following compounds of the instant invention:
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Schroder, Table 2, p. 179.
Therefore, claims 1 and 5-20 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
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. 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 provisional rejection of claims 1 and 5-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/030,639 in view of Peterson et al. (US 8,377,701 B2, published Feb. 19, 2013) is maintained.
Response to Arguments
The Applicant argues that one of ordinary skill in the art would not have a motivation or reasonable expectation of success to combine Peterson with the copending Application because the compounds of the instant and copending Application are different from those of Peterson (Remarks, p. 10). These arguments were fully considered but are not persuasive. Both Peterson, the instant application and the copending Application are directed towards sortilin inhibitors. It would be well within the level of ordinary skill to apply a method of treating a condition with one sortilin inhibitor to a method of treating that same condition with another sortilin inhibitor. There is a clear reasonable expectation of success because the biochemical target is the same and the intended outcome is the same. The exact structure of the compound accomplishing this function is irrelevant because it is clear from the copending application and the prior art that either structure can accomplish the intended result.
Reiterated Rejection
Although the claims at issue are not identical, they are not patentably distinct because the instant claims are directed towards a method of treating diabetic retinopathy with sortilin inhibitors of formula (I) and the copending claims are directed towards a method of treating hearing loss with sortilin inhibitors of formula (I). One of ordinary skill in the art would have a reasonable expectation of success to apply the compounds of formula (I) to either diabetic retinopathy or hearing loss because Peterson teaches that sortilin inhibitors are useful for both the treatment of diabetic retinopathy and hearing loss:
In one aspect the present invention relates to a medicament comprising an inhibitor of Sortilin and/or of Sortilin:proNGF:p75NTR induced apoptosis.
In one embodiment of the present invention the at least one ligand as identified by the methods described herein above is used for the manufacture of a medicament, wherein said medicament is for the treatment, and prevention or treatment and prevention of and/or protection against a disease, disorder, or damage of the nervous system in an individual.
Peterson, Specification, col. 37, lines 14-22;
In one embodiment of the present invention the nervous system disorder, disease, or damage involves the retina, photoreceptors, and associated nerves.
In one embodiment of the present invention the nervous system disorder, disease, or damage involving the retina, photoreceptors, and associated nerves is selected from the group consisting of retinitis pigmentosa, macular degeneration, glaucoma, and diabetic retinopathy.
In one embodiment of the present invention the nervous system disorder, disease, or damage involves the sensory epithelium and associated ganglia of the vestibuloacoustic complex.
In one embodiment of the present invention said nervous system disorder, disease, or damage involving the sensory epithelium and associated ganglia of the vestibuloacoustic complex is selected from the group consisting of noise-induced hearing loss, deafness, tinnitus, otitis, labyrintitis, hereditary and cochleovestibular atrophies, and Menieres Disease.
Peterson, Specification, col. 38, lines 14-32 (emphasis added).
Claims 16-20 are newly added but read on the same compounds of formula (I) mentioned above and are thus rejected on the same grounds as above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is found to be allowable.
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 extension fee 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 HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629