DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Preliminary Amendment filed 29 February 2024, Applicant cancelled claims 1-24 and added twenty-three new claims, i.e., claims 25-47. Claims 25-47 are pending.
Claim Objections
Claims 28, 36, and 43 are objected to because of the following informality: The use of capital letters for generic names of materials, devices, or delivery systems is inappropriate. Generally, capital letters are reserved for the beginning of a claim, for abbreviations, and for trademarks/tradenames. Appropriate correction is required.
Claim Rejections - 35 U.S.C. 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 25-27, 29-35, 37-42, and 44-47 are rejected under 35 U.S.C. 103 as being unpatentable over Yorio (US 2003/0176356 A1) in view of Davenport (“Endothelin.” Pharmacological reviews 68.2 (2016): 357-418), Eggenweiler (US 2004/0063731 A1), and Shoshani (“Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma.” Current eye research 37.1 (2012): 1-11).
Yorio is directed to endothelin antagonists for the treatment of glaucoma. Title/Abstract.
Yorio discloses that “Endothelins (‘ET’) are potent vasoactive peptides that are implicated in the development and progression of certain forms of glaucoma (e.g. primary open-angle and normal tension glaucomas), which results in the apoptotic death of retinal ganglion cells and progressive cell death leads to blindness.” Para. [0010].
Yorio discloses that an effective amount of an ET antagonist in a pharmaceutically acceptable vehicle can be administered to treat glaucoma. Paras. [0014], [0015], [0088], and [0095].
Yorio discloses that the “ET antagonist(s) may be administered systemically, topically, by intraocular injection, intraocular perfusion, periocular injection or retrobulbar injection.” (Emphasis added) Para. [0087]; see also paras. [0014] and [0026]. An exemplary intraocular injection formulation is disclosed in Example 10. Para. [0097].
Yorio discloses: “ET antagonist(s) of the present invention are represented generically in the examples as ‘ET antagonist.’ However, the drugs listed in Tables 1 and Table 2 are representative agents in these classes. The invention includes any agent related in structure and pharmacology to these agents.” (Emphasis added) Para. [0095].
Although Yorio identifies several compounds as exemplary ET antagonists in Table 2 (para. [0132]), Yorio is silent regarding edonentan. Consequently, Yorio does not satisfy any of the three independent claims of the present application (i.e., claims 25, 33, and 41). As explained below, the following three references compensate for this deficiency: Davenport, Eggenweiler, and Shoshani.
Davenport is a pharmacological review directed to endothelins and antagonists thereof. Abstract.
Davenport teaches that edonentan, also known as BMS-207940, is an endothelin (ET) antagonist undergoing clinical trials. Page 392 at Table 5.
Eggenweiler is directed to a pharmaceutical preparation comprising at least one phosphodiesterase V inhibitor have, and/or physiologically acceptable salts and/or solvates thereof and at least one endothelin receptor antagonist for the preparation of a medicament for the treatment of various medical conditions, for example, glaucoma. Abstract.
Eggenweiler teaches that BMS-207940 (edonentan) is a preferred endothelin receptor antagonist. Para. [0117]; see also claims 10, 25, and 40.
Eggenweiler teaches that the endothelin receptor antagonist can be administered to treat glaucoma. Paras. [0043], [0453], [0667], and [0870]; see also claims 13, 28, and 43.
Shoshani is directed to endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma. Title.
Shoshani teaches that “several endothelin antagonists have shown benefit in the treatment of pulmonary arterial hypertension and have been shown to have a potential role in glaucoma therapy” and the “[r]ecent findings suggest that endothelin inhibition may improve ocular blood flow, thus affecting ocular function and ocular vascular parameters.” (Emphasis added) Page 2, left column.
Shoshani teaches that the efficacy of endothelin antagonists can be evaluated by improvement in choroidal and optic nerve head blood flow. Page 2 at paragraph bridging the left and right columns; see also page 4, right column (“In anesthetized cats, intravitreal injection of ET-1 [endothelin] resulted in a dose-dependent and sustained reduction of optic nerve head blood flow”).
Before the effective filing date of the claimed invention, the teachings of Davenport, Eggenweiler, and Shoshani would have motivated a person having ordinary skill in the art to modify Yorio by selecting edonentan as the endothelin antagonist, in an effort to yield a more effective treatment for glaucoma. The foregoing modification would have been made with a reasonable expectation of success, especially considering (i) Davenport teaches edonentan is undergoing clinical trials as an endothelin antagonist and (ii) Eggenweiler teaches edonentan can be administered to treat glaucoma. MPEP § 2143.02(I) (“Where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success.”).
Eggenweiler teaches that the endothelin receptor antagonists identified therein (e.g., edonentan) are preferably administered in doses of between about 1 and 500 mg per dosage unit to treat glaucoma. Paras. [0452]-[0453], [0666]-[0667], and [0869]-[0870]. The low end of the foregoing range (about 1 mg) is overlapped by the corresponding range recited in claim 33 (“about 50 µg to about 4 mg”). MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”). Additionally, Yorio discloses: “The exact dosage of one or more ET antagonist(s) to be administered to the patient will vary, but will be determined by clinicians skilled in the art. Various factors affecting the dosage amount include the actual disease to be treated, the severity of condition, the health of the patient, the potency and specific efficacy of the ET antagonist(s), and so on. The amount dosed, however, will be an ‘effective amount.’ As used herein, the term ‘effective amount’ is an amount, which inhibits ET’s activity at a level effective for therapy.” Para. [0088]. The foregoing disclosure is also sufficient to establish prima facie obviousness on the basis of routine experimentation. MPEP § 214405(II)(A) (“‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’”), quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Both the patient population (glaucoma patients) and the treatment regimen (injecting an effective amount of edonentan into optical tissue) recited in claims 25, 33, and 41 of the present application are taught by Yorio in view of Davenport, Eggenweiler, and Shoshani, as applied above. Those three claims, along with claims 26 and 34, focus on alleviating symptoms or complications closely associated with glaucoma, rather than treating glaucoma, itself. See claim 25 (“improving a visual function”), claim 33 (“improving a visual function”), and claim 41 (“improving optic nerve head blood flow”). However, that difference is not patentably significant because the “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” MPEP § 2145(II), citing In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Stated another way, the claimed additional advantage of alleviating various symptoms or complications closely associated with glaucoma flows naturally from following the teachings of Yorio in view of Davenport, Eggenweiler, and Shoshani. MPEP § 2145(II) (“‘The fact that appellant 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.’”), quoting Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). The recitation of an additional advantage associated with doing what is suggested by Yorio in view of Davenport, Eggenweiler, and Shoshani does not lend patentability to an otherwise unpatentable invention. MPEP § 2145(II).
Therefore, claims 25-26, 33-34, and 41 are prima facie obvious.
Regarding claims 27, 29-32, 35, 37-40, 42 and 44-47, Yorio discloses that “endothelin levels may be high in the back of the eye from retinal sources, and these increases in endothelin have detrimental and pathophysiological effects on the optic nerve” (para. [0047]) and suggests delivering the endothelin antagonist to the back of the eye for that reason (para. [0080]). Yorio additionally discloses intravitreal delivery, intraocular injections, and retrobulbar injections. Paras. [0087]-[0089] and page 14 at claim 17 (“whereby administering the effective amount of one the ET antagonist is selected from a group consisting of retrobulbar injection, intracameral delivery, intravitreal delivery”). In further regard to claims 29-32, 37-40 and 44-47, the dosing frequency is subject to routine experimentation. MPEP § 214405(II)(A) (“‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’”), quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955). Applicant is referred above to the discussion of claim 33 and to paragraph [0088] of Yorio.
Claims 28, 36, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Yorio in view of Davenport, Eggenweiler and Shoshani, as applied above to claims 25-27, 29-35, 37-42, and 44-47, and further in view of Morrison (US 5,364,374).
Although Yorio discloses that the endothelin antagonist can be administered by intravitreal, intraocular, or retrobulbar injection, Yorio is silent as to whether those injections can be performed using a microneedle injector, which is recited in claims 28, 36, and 43. As explained below, Morrison compensates for this deficiency.
Morrison is directed to a microneedle for injection of ocular blood vessels. Title.
Morrison teaches that the microneedle disclosed therein is specifically intended for use in treating glaucoma. Abstract and column 1, lines 14-19.
Morrison teaches that the microneedle permits the efficient delivery of glaucoma medication into the eye, thereby overcoming the problem of poor drug penetration by eye drop formulations, while advantageously avoiding undesirable systemic effects. Column 1, lines 42-51; column 1, line 65 to column 2, line 6; and column 2, lines 39-58.
Before the effective filing date of the claimed invention, a person having ordinary skill in the art would have been motivated to modify Yorio by selecting the microneedle taught in Morrison as the injection device for the anti-glaucoma edonentan formulation. Therefore, claims 28, 36, and 43 are prima facie obvious. MPEP § 2144.07 (the selection of a known device based on its suitability for its intended use can support a prima facie obviousness determination).
Claim Rejections - Double Patenting (Non-Statutory)
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 obviousness-type 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR1.321(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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 eTerminalDisclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/ eTD-info-I.jsp.
Claims 25-47 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-11 of Patent No. 11,738,007 alone or in view of Shoshani (“Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma.” Current eye research 37.1 (2012): 1-11).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 1 of the ’007 Patent is directed to “[a] method of treating glaucoma in a subject in need thereof, comprising: injecting a composition comprising a therapeutically effective amount of edonentan or a pharmaceutically acceptable salt thereof, into an optical tissue of said subject having glaucoma.” The effective amounts recited in conflicting claims 3-5, the drug delivery systems recited in conflicting claim 6, the modes of delivery (i.e., injection to the back of the eye) recited in conflicting claims 7-8, and the dosing frequencies recited in conflicting claims 9-11 match the corresponding limitations recited in the claims of the present application.
Both the patient population (glaucoma patients) and the treatment regimen (injecting edonentan to the back of the eye) recited in the conflicting claims are the same as those recited in the present claims. The difference, to the extent there is one, is that the three independent claims of the present application focus on alleviating symptoms or complications closely associated with glaucoma, rather than treating glaucoma, itself. See claim 25 (“improving a visual function”), claim 33 (“improving a visual function”), and claim 41 (“improving optic nerve head blood flow”). However, that difference is not patentably significant because the “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” MPEP § 2145(II), citing In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Stated another way, the claimed advantage of alleviating various symptoms or complications closely associated with glaucoma flows naturally from following the treatment protocol for glaucoma disclosed in the conflicting claims of the ’007 Patent. The recitation of an additional advantage associated with doing what the claims of the ’007 Patent disclose does not lend patentability to an otherwise unpatentable invention. MPEP § 2145(II).
Even if there were a deficiency in the conflicting claims regarding “improving optic nerve head blood flow” (present claim 41) and/or “improving a visual function” (present claims 25 and 33), Shoshani compensates for any such deficiency by teaching that “several endothelin antagonists have shown benefit in the treatment of pulmonary arterial hypertension and have been shown to have a potential role in glaucoma therapy” and the “[r]ecent findings suggest that endothelin inhibition may improve ocular blood flow, thus affecting ocular function and ocular vascular parameters.” (Emphasis added) Page 2, left column.
In conclusion, the present claims are not patentably distinguishable over conflicting claims 1-11 of the ’007 Patent.
Conclusion
Claims 25-47 are rejected.
Claims 28, 36, and 43 are also objected to.
No claim is allowed.
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/P.A./
01 November 2025
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611