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 .
Claims 1-20 are presented for examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 11-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating retinal ischemia, does not reasonably provide enablement for preventing retinal ischemia. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The claims are drawn to a method of preventing or treating retinal ischemia disease in a subject, comprising: administering an effective amount of a preservative-free ophthalmic pharmaceutical emulsion to eyes of the subject, wherein the preservative-free ophthalmic pharmaceutical emulsion comprises 0.01% w/v to 0.1% w/v latanoprostene bunod or a pharmaceutically acceptable salt thereof, 0.2% w/v to 0.7% w/v an oil, 0.4% w/v to 1.4% w/v a surfactant, and at least one pharmaceutical excipient, wherein the HLB values of the oil and the surfactant are calculated together to form a required hydrophilic-lipophilic balance (rHLB) value in a range from 10 to 16.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1) The Nature of the Invention:
The rejected claims are drawn to a method of preventing or treating retinal ischemia disease in a subject, comprising: administering an effective amount of a preservative-free ophthalmic pharmaceutical emulsion to eyes of the subject, wherein the preservative-free ophthalmic pharmaceutical emulsion comprises 0.01% w/v to 0.1% w/v latanoprostene bunod or a pharmaceutically acceptable salt thereof, 0.2% w/v to 0.7% w/v an oil, 0.4% w/v to 1.4% w/v a surfactant, and at least one pharmaceutical excipient, wherein the HLB values of the oil and the surfactant are calculated together to form a required hydrophilic-lipophilic balance (rHLB) value in a range from 10 to 16.
(2) Breadth of the Claims:
The instant claims embrace a method of preventing retinal ischemia.
(3) Guidance of the Specification / Working Examples:
In the instant case, no working examples are presented in the specification as filed showing how to prevent retinal ischemia in a human or animal totally, or permanently or not even occurring at the first time.
(4) State/Predictability of the Art:
The relative skill of those in the art is high with respect to treating a specific eye disease employing a specific compound.
However, the relative skill of those in the art is low with respect to preventing retinal ischemia using latanoprostene bunod or a pharmaceutically acceptable salt thereof in a human or animal, not even occurring at the first time. The relative skill in the art and predictability is low with respect “To prevent”, which actually means to anticipate or counter in advance, to keep from happening. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher, 427 F.2d 833, 839 (1970). Applicant’s attention is drawn to the attached article by Fortmann (Molecular mechanisms of retinal ischemia), which teaches that the retina is particularly susceptible to ischemia given its immense metabolic needs. The molecular responses to
retinal ischemia are multifaceted, and include pathways involved in metabolism, inflammation, and vascular homeostasis, among others. While these pathways are designed to protect the retina from hypoxia and nutrient deprivation, they often lead to exudation, pathological vessel growth, and vision loss. A current focus in the field is to determine which of these molecular responses are
causative versus consequential, so that clinical interventions may be developed that effectively prevent disease progression. The discovery of VEGF as a central mediator in the progression of retinal ischemia and the subsequent development of anti-VEGF agents has preserved vision in millions of patients [56,57]. Even with the remarkable benefits of anti-VEGF agents, some patients still experience disease progression, highlighting the need for new treatments that target ischemic retinopathies from different perspectives. The recent studies highlighted in this review represent significant advances in understanding the molecular mechanisms responsible for retinal ischemia and may be influential in the development of novel treatment. Such teaching by the attached article indicates the difficulties in treating retinal ischemia, nevertheless preventing such disorder.
Additionally, in order to prevent the occurrence of a condition/disease, one has to be able to determine a person susceptible to said condition/disease. The state of the art is such that no method(s) is known for said determination. In essence, if one cannot determine a person in need of preventative therapy and/or the art nor the present specification teach how the skilled artisan could utilize the claimed composition to "prevent" retinal ischemia recited by the instant claims, applicant has not enabled the full scope of the claimed invention.
Thus, the skilled artisan would view that preventing retinal ischemia in a patient in need of such treatment is highly unpredictable by employing latanoprostene bunod or pharmaceutically acceptable salt thereof. Therefore, the skilled artisan would view that the ability to prevent retinal ischemia in a human or animal totally, or permanently, not even occurring at the first time is highly unpredictable.
(5) The Quantity of Experimentation Necessary:
Applicant fails to provide information sufficient to practice the claimed invention, absent undue experimentation.
Genentech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors, e.g., the amount of direction or guidance provided, absence of working examples, and the predictability of the art discussed above, to practice the claimed invention herein, a person of skill in the art would have to test the compound in the instant claims to be administered to a host employed in the claimed methods of the particular treatments herein, with no assurance of success.
Accordingly, the claims are evaluated as a method of treating retinal ischemia and not he method of prevention retinal ischemia.
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.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Belkin (US 20230064711) in view of Karavas et al. (US 2019117562) and further in view of Khopade et al. (US 20100137432), Ishida et al. (US 9,138,438) and Mehran et al. (New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost).
The Claims are drawn to a preservative-free ophthalmic pharmaceutical emulsion, comprising:
0.01% w/v to 0.1% w/v latanoprostene bunod or a pharmaceutically acceptable salt thereof,
0.2% w/v to 0.7% w/v an oil,
0.4% w/v to 1.4% w/v a surfactant, and
at least one pharmaceutical excipient,
wherein the HLB values of the oil and the surfactant are calculated together to form a required hydrophilic-lipophilic balance (rHLB) value in a range from 10 to 16.
Claims 11-16 are drawn to a method of preventing or treating retinal ischemia using the composition of claim 1.
Claims 17-20 are drawn to a method of treating glaucoma using the composition of claim 1.
Regarding claim 1, Belkin teaches a pharmaceutical composition comprising between about 0.001% and about 10% of one or more of latanoprost, bimatoprost, travoprost, taflupros, latanoprostene bound, any pharmaceutically acceptable salt thereof, solvate thereof, hydrate thereof, any stereoisomer therefore, physiologically functional derivative thereof or any combinations thereof. See Para [0164]. The use of oils, such as vegetable derived oils is taught in Paras [0177] and [0216]. The use of anionic, cationic and non-ionic surfactants is taught in Para [0216]. The use of carriers is taught in Para [0074]. The composition being in an oil in water emulsion, water in oil emulsion is taught in Para [0219]. The use of an excipient is taught in Para [0054].
Belkin does not teach a preservative free composition, the concentrations and the HLB values of the oil and the surfactant.
Karavas teaches a preservative-free ophthalmic composition for the reduction of elevated intraocular pressure containing Latanoprost. See the abstract. Karavas makes clear that latanoprost ophthalmic formulation is prepared without preservatives. It would have been obvious to a person skilled in the art to prepare the claimed compound, latanoprostene bunod, which is a derivative of latanoprost, preservative free in the absence of evidence to the contrary. Khopade teaches the use of surfactants having HLB value of more than 10. See Para [0056]. The determination of optimum proportions or amounts are considered to be within the skill of artisan in the absence of evidence to the contrary. Applicant’s attention is drawn to In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955, where the court stated, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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”.
Regarding claim 2, Belkin does not teach the use of castor oil, olive oil or sesame oil. However, Khopade et al. teach a pharmaceutical composition suitable for ophthalmic use comprising one or more prostaglandin derivatives or salts, a stabilizing amount of polyethylene glycol hydroxystearate and pharmaceutically acceptable vehicle. See the abstract. The use of castor, olive and sesame oil is taught in Para [0056].
Regarding claim 3, Belkin does not teach the use of polyethylene glycol hydroxystearate. However, Khopade teaches the use of polyethylene glycol hydroxystearate as a surfactant in an ophthalmic composition comprising prostaglandin derivatives. See Para [0057].
Regarding claims 4 and 5, Belkin does not teach at least one excipient being a chelating agent, a pH adjuster or a solvent. However, Khopade teaches the use of a chelating agent, such as EDTA in ophthalmic formulations with prostaglandins as old and well known. See Para [0072].
Regarding claim 6, Belkin teaches the use of propylene glycol in an ophthalmic composition comprising latanoprostene bunod. See Para [0188]. The determination of optimum proportions and amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claims 7-9, Belkin does not teach the use of olive, sesame and castor oil. However, Khopade et al. teach a pharmaceutical composition suitable for ophthalmic use comprising one or more prostaglandin derivatives or salts, a stabilizing amount of polyethylene glycol hydroxystearate as claimed in claims 7-9 and pharmaceutically acceptable vehicle. See the abstract. The use of castor, olive and sesame oil as claimed in claims 7-9 is taught in Para [0056]. The use of EDTA as claimed in claims 7-9 is taught in Para [0072] of Khopade. The determination of optimum proportions or amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 10, Belkin does not teach the particle size of the composition. However, the determination of particle size distribution of the composition is considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claims 11-15, Belkin does not teach the use of the claimed prostaglandin for the treatment of retinal ischemia. However, Ishida et al. teach the use of prostaglandin F2alpha, such as latanoprost derivatives for the treatment of retinal neuronal death due to ischemia. See the abstract and column 1, lines 55-65.
Mehran et al. teach the use of the claimed compound, latanoprostene bunod for the treatment of glaucoma and regulation of ocular blood flow , which may promote retinal ganglion cell survival in the eye.
Regarding claim 16, Belkin teaches that the pharmaceutical compositions may be prepared in a dosage form that is suitable to be administrated topically to the conjunctiva, the cornea or the eyelid or administrated parenterally, e.g. intraocular injection to the anterior, posterior and vitreous chambers.
Regarding claims 17 and 18 Belkin teaches the use latanoprostene bunod for the treatment of glaucoma. See Claim 41. The use of oils, such as vegetable derived oils is taught in Paras [0177] and [0216]. The use of anionic, cationic and non-ionic surfactants is taught in Para [0216]. The use of carriers is taught in Para [0074]. The composition being in oil in water emulsion, water in oil emulsion is taught in Para [0219]. Belkin does not teach the use of the composition being preservative free, the use of castor, olive and sesame oil and HLB values of the oil and the surfactant being from 110-16. However, Khopade teaches the use of surfactants and oils having HLB value of more than 10 in ophthalmic formulations comprising prostaglandins. See Para [0056]. The use of castor, olive and sesame oil as claimed in claim 18 is taught in Para [0056]. Karavas teaches a preservative-free ophthalmic composition for the reduction of elevated intraocular pressure containing Latanoprost. See the abstract.
Regarding claim 19, Belkin teaches the use of latanoprostene bunod for the treatment of glaucoma. The reduction of intraocular pressure and increase blur rate of retinal vessel area is the inherent property of using latanoprostene bunod for treating glaucoma as taught by Belkin.
Regarding claim 20, Belkin teaches, the pharmaceutical compositions may be prepared in a dosage form that is suitable to be administrated topically to the conjunctiva, the cornea or the eyelid or administrated parenterally, e.g. intraocular injection to the anterior, posterior and vitreous chambers. See Para [0171].
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617