DETAILED CORRESPONDENCE
This office action is in response to applicant’s filing dated August 26, 2026.
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 .
Status of Claims
Claims 1-19 are pending in the instant application.
Election of Species
Applicant’s election of i) age-related macular degeneration as the elected disease species, ii) spironolactone as the elected mineralocorticoid receptor antagonist species; and iii) a formulation species further comprising bevacizumab in the reply filed on August 26, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 4-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 26, 2026.
Claims 1-3 and 7-19 are presently under examination as they relate to the elected species: age-related macular degeneration, spironolactone, and bevacizumab.
Priority
The present application is a CON of US Application No. 17/701,884 filed on March 23, 2022, which is a CON of US Application No. 15/765,756 filed on April 4, 2018, which is a 371 of PCT/EP2016/074470 filed on October 12, 2016, which claims benefit of foreign priority to EPO 15306617.0 filed on October 13, 2015.
Drawings
Acknowledgement is made of the drawings on July 29, 2024. These drawings are accepted.
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.
Claims 1-3, 7, and 10-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Behar-Cohen et al (WO 2011/141456 A1).
Regarding claims 1-3, 7 and 11, Behar-Cohen teaches a mineralocorticoid receptor antagonist for use in the treatment of age related macular degeneration (claim 1); the mineralocorticoid receptor antagonists according to the invention generally are spirolactone-type steroidal compounds; a subclass of spirolactone-type antagonist compounds consists of non-epoxy-steroidal mineralocorticoid receptor antagonist compounds (page 5, 3rd paragraph); of particular interest is the compound spironolactone (page 12, last paragraph).
Regarding the limitation wherein the MR antagonist is administered to the subject in the form of micro or nanospheres, the Examiner notes that the instant specification discloses the term “microsphere” has general meaning in the art and refers to a small diameter or dimension device or clement that is structured, sized, or otherwise configured to be administered subconjunctivally (i.e. sub-tenon) or into the vitreous; microspheres included particles (see instant specification page 17, 1st paragraph) and that microspheres may be of any particulate geometry including micro and nanospheres, micro and nanoparticles, spheres, powders, fragments and the like. The upper limit for the microsphere size will be determined by factors such as toleration for the implant, size limitations on insertion, desired rate of release, case of handling, etc. Spheres may be in the range of about 0.5 μm to 4 mm in diameter, with comparable volumes for other shaped particles (see instant specification 18, last bridge paragraph).
Behar-Cohen teaches the active ingredient can comprise from about 10% to about 90% by weight of the implant (page 30, lines 1-2); the implants may be formed as particles, may be of any size or shape compatible with the selected site of implantation; for example, the vitreous chamber is able to accommodate relatively large rod-shaped implants, generally having diameters of about 0.05 mm to 3 mm and a length of about 0.5 to about 10 mm; in one variation, the rods have diameters of about 0.1 mm to about 1 mm (page 32, lines 6-13).
Thus, Behar-Cohen specifically teaches administration of the composition in the form of microspheres into the vitreous.
Regarding claims 10 and 12, Behar-Cohen teaches preferably local ocular routes should be used such as intravitreous and periocular injections including supra choroidal (page 26, 2nd paragraph). Intravitreous reads on into the vitreous.
Thus, the teachings of Behar-Cohen anticipates the method of instant claims 1-3, 7, and 10-12.
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 should 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.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al (WO 2011/141456 A1) as applied to claims 1-3, 7, and 10-12 above.
As set forth above, Behar-Cohen teaches a method of treating age related macular degeneration comprising administering a composition comprising spironolactone, wherein the composition is in the form of microspheres, and the composition is injected into the vitreous.
Regarding the claimed amount of the MR antagonist of instant claims 13 and 14, Behar-Cohen teaches the active ingredient can comprise from about 10% to about 90% by weight of the implant (page 30, lines 1-2); the implants may be formed as particles, may be of any size or shape compatible with the selected site of implantation; for example, the vitreous chamber is able to accommodate relatively large rod-shaped implants, generally having diameters of about 0.05 mm to 3 mm and a length of about 0.5 to about 10 mm; in one variation, the rods have diameters of about 0.1 mm to about 1 mm (page 32, lines 6-13).
MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Taken together, all this would result in the practice of the method of claims 13 and 14 with a reasonable expectation of success.
Claims 8 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al (WO 2011/141456 A1) as applied to claims 1-3, 7, and 10-14 above, and further in view of Naveed et al (WO 2008/063932 A2).
Behar-Cohen teaches all the limitations of claims 8 and 15 (see above 102 and 103 rejections), except wherein the MR antagonist is administered to the subject in combination with an anti-VEGF agent.
However, Naveed teaches a method of treating wet-form age-related macular degeneration (AMD) in an eye of a patient who has had previous VEGF antagonist therapy comprising administering a dose of a VEGF antagonist (claim 1) where in the VEGF antagonist is an anti-VEGF antibody (claim 6). Moreover, Naveed teaches anti-VEGF antagonistic antibodies include rhuMAB VEGF (bevacizumab).
Before the effective filing date of the invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat age-related macular degeneration combining two compositions (spironolactone and bevacizumab) each of which is taught by the prior art to be useful for the same purpose (i.e., age-related macular degeneration), in order to form a third composition to be used for the same purpose. The idea of combining them flows logically from there having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Taken together, all this would result in the practice of the method of claims 8 and 15 with a reasonable expectation of success.
Claims 9 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al (WO 2011/141456 A1) as applied to claims 1-3, 7, and 10-12 above, and further in view of Oliveira Dias et al (Br J Ophthalmol, 2011; 95:2631-1637).
Behar-Cohen teaches all the limitations of claim 9 (see above 102 rejection), except wherein the subject is refractory to an anti-VEGF treatment.
However, Behar-Cohen does teach that high doses of corticosteroids are currently injected into the vitreous cavity of patients with macular edema because of their anti-inflammatory effects (page 34, lines 1-2) and MR antagonism reduced the pathological angiogenesis associated with inflammation (page 44, lines 13-14). Thus, Behar-Cohen teaches mineralocorticosteroid antagonists are anti-inflammatory agents.
Moreover, Oliveira Dias teaches inflammatory and angiogenic pathways become more numerous and redundant as disease progresses; considering this, it is unlikely that inhibiting one factor or pathway will produce a sustained clinical effect in patients with previously treated, highly refractory disease; the fact that inflammation appears early in age-related macular degeneration (AMD) pathology may explain why anti-inflammatory agents are beneficial as preventive or adjunctive therapies for patients who do not respond to conventional anti-VEGF therapy (page 1635, left, last paragraph).
As such, since Behar-Cohen teaches a method of treating age-related macular degeneration comprising administering a mineralocorticosteroid antagonist, spironolactone and that mineralocorticosteroid antagonists are anti-inflammatory agents, and since Oliveira Dias teaches anti-inflammatory agents are beneficial as preventive or adjunctive therapies for patients who do not respond to conventional anti-VEGF therapy, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the invention to treat age-related macular degeneration in a subject that is refractory to anti-VEGF treatment with spironolactone with an expectation of success, since the prior art establishes that spironolactone is a mineralocorticosteroid antagonist useful for treating age-related macular degeneration, mineralocorticosteroid antagonists are anti-inflammatory agents and anti-inflammatory agents are beneficial as preventive or adjunctive therapies for patients who do not respond to conventional anti-VEGF therapy.
Taken together, all this would result in the practice of the method of claims 9 and 16-19 with a reasonable expectation of success.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al (WO 2011/141456 A1) in view of Naveed et al (WO 2008/063932 A2) and Oliveira Dias et al (Br J Ophthalmol, 2011; 95:2631-1637).
As set forth above, Behar-Cohen teaches a method of treating age related macular degeneration comprising administering a composition comprising spironolactone, wherein the composition is in the form of microspheres, and the composition is injected into the vitreous.
Behar-Cohen does not explicitly teach the method comprises administering spironolactone in combination with an anti-VEGF treatment or that the age-related macular degeneration is non-responsive or insufficiently responsive to anti-VEGF.
However, Behar-Cohen does teach that high doses of corticosteroids are currently injected into the vitreous cavity of patients with macular edema because of their anti-inflammatory effects (page 34, lines 1-2) and MR antagonism reduced the pathological angiogenesis associated with inflammation (page 44, lines 13-14). Thus, Behar-Cohen teaches mineralocorticosteroid antagonists are anti-inflammatory agents.
Moreover, Oliveira Dias teaches inflammatory and angiogenic pathways become more numerous and redundant as disease progresses; considering this, it is unlikely that inhibiting one factor or pathway will produce a sustained clinical effect in patients with previously treated, highly refractory disease; the fact that inflammation appears early in age-related macular degeneration (AMD) pathology may explain why anti-inflammatory agents are beneficial as preventive or adjunctive therapies for patients who do not respond to conventional anti-VEGF therapy (page 1635, left, last paragraph).
Naveed teaches a method of treating wet-form age-related macular degeneration (AMD) in an eye of a patient who has had previous VEGF antagonist therapy comprising administering a dose of a VEGF antagonist (claim 1) where in the VEGF antagonist is an anti-VEGF antibody (claim 6). Moreover, Naveed teaches anti-VEGF antagonistic antibodies include rhuMAB VEGF (bevacizumab).
Before the effective filing date of the invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat age-related macular degeneration combining two compositions (spironolactone and bevacizumab) each of which is taught by the prior art to be useful for the same purpose (i.e., age-related macular degeneration), in order to form a third composition to be used for the same purpose. The idea of combining them flows logically from there having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Furthermore, one of ordinary skill in the art before the effective filing date would have a reasonable expectation of success of utilizing the combined treatment of spironolactone and bevacizumab for treating age-related macular degeneration for treating age-related macular degeneration refractory (non-responsive or insufficiently responsive) to anti-VEGF treatment alone, since the prior art teaches both spironolactone and bevacizumab are useful for treating age-related macular degeneration, mineralocorticosteroid antagonists are anti-inflammatory agents and anti-inflammatory agents are beneficial as preventive or adjunctive therapies for patients who do not respond to conventional anti-VEGF therapy.
Taken together, all this would result in the practice of the method of claim 19 with a reasonable expectation of success.
Conclusion
Claims 1-3 and 7-19 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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