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 .
Claim Rejections - 35 USC § 112
The following is a quotation 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 of carrying out his invention.
Claims 23-25 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 formulations that treat lens diseases in humans or animals, does not reasonably provide enablement for formulations that prevent lens diseases of humans and animals. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by 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 quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The invention relates to compositions that treat and prevent lens diseases in humans and animal composed of oxysterols as the drug active along with excipients that include surfactant, cosolvent, thickener, and water. The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. Lens diseases are known to include those that are genetic or acquired over time. Cataracts are a known lens disease that can be congenital and occur at birth, due to a traumatic impact, or develop over time due to age or other conditions (see Liu et al. Lancet 2017 390:600-612; page 600).
The claims embrace compositions with a prescribed relative ratio of surfactant, cosolvent, thickener, and oxysterol that can prevent all lens disease. Lanosterol and 25-hydroxycholesterol are the two specifically claimed oxysterol compounds. The compositions are also recited as topical. As such, the opportunity to employ a topical eye composition for a condition that occurs at birth or occurs due to a trauma is not available. While cataracts are treated and the severity of the occurrence of chemically induced cataracts is reduced in animal experiments detailed in the instant specification, cataract prevention was not achieved.
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed product could be made. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites ‘active substances…are oxysterols”. It is unclear if a combination of oxysterols is required or if a single oxysterol is sufficient. Since subsequent claims refer to “the oxysterol”, the latter interpretation will be employed for the sake of the application of prior art.
Regarding claims 5, 11-12, 18, 20, and 24-25, the term "preferably" renders the claims indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 1, 8-10, and 18, the term "including" or “include” renders the claims indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d).
Claim 18 has several instances of a parenthetical recitation following a generic term. The recitation in the paratheses recites a subset of options within the generic category, thus it is a broad limitation followed by a narrower limitation. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The recitations are indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The scope of claims 24 and 25 is unclear. Both claims recite “the use according to claim 23”, but claim 23 is drawn to a formulation, not a use. In addition, there are no method steps recited by claims 24 and 25 that make use of the formulation of claim 23. Thus it is unclear if a product is being claimed and how the recitations further limit the scope of the formulation of the parent claim.
Claims not explicitly elaborated upon are also indefinite because they depend from an indefinite claim and do not add clarity.
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.
Claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (CN 106344587 – English translation referenced for citations).
Cheng et al. teach a composition for topical application to the eye for the treatment of cataracts (see abstract and paragraphs 2 and 25). They go on teach the composition to contain lanosterol as well as a pharmaceutically acceptable carrier that may include a combination of water, solubilizer (cosolvent), surfactant, and thickening agent as well as preservative and buffer (see paragraphs 11, 30, 40-50, and 83-88; instant claims 1 and 12). They further detail the composition with 10 to 50 mM lanosterol, 0.1 to 50 wt% polyhydroxy compound (cosolvent), 0 to 1 wt% solubilizer/surfactant, 0.2 to 0.4 wt% thickener, 0 to 0.5 wt% preservative, and the remainder water (see paragraphs 80-87). The lanosterol concentration corresponds to approximately 0.43 to 2 wt% (as calculated by the examiner based on a 426 g/mol molar mass and composition density of 1 g/ml). Broader teachings of the composition envision the polyhydroxy compound at up to 50 wt%, surfactant at up to 2 wt%, and thickener up to 6 wt% (see paragraphs 71-73). They teach parabens as a preferred preservative, propylene glycol as a preferred polyhydroxy compound, and polysorbate as a preferred surfactant (see paragraphs 56, 59, and 84-85; instant claims 6-7, 13, and 18). Zheng et al. also teach hydroxypropylmethylcellulose as well as povidone as thickeners employed individually and in combination (see paragraph 60; instant claims 8 and 10). Further, they teach production of the composition, where the lanosterol is dispersed in the pharmaceutical carrier (see paragraphs 90-98; instant claim 18). They additionally teach topical administration to treat cataracts (see paragraph 99; instant claims 23-25).
While a full example for each embodiment that follows from the teachings of Zheng et al. is not detailed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the composition of Zheng et al. where lanosterol, water, propylene glycol, polysorbate, and parabens along with hydroxypropylmethylcellulose and/or povidone are the pharmaceutically acceptable carrier. This choice would have been obvious because these components are preferred options for the combination of excipient categories discussed by Zheng et al. It additionally would have been obvious to apply their taught proportions for these ingredients. The result is greater than 0 to 2 wt% polysorbate (surfactant), 0.2 to 6 wt% thickening agent, 0.1 to 50 wt% propylene glycol (cosolvent), and 0.43 to 2 wt% (4.3 to 20 mg/ml) lanosterol, due to the teachings of Zheng et al. of ranges or discrete values that produce a range (see MPEP2144.05; instant claims 1 and 4). These ranges yield a range of ratios that overlap with those instantly claimed, thereby rendering the claimed ranges obvious. “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)” (see MPEP 2144.05). In addition, it would have been obvious to prepare the composition where the pharmaceutically acceptable carrier is provided and lanosterol is dispersed within it because they suggest to do so. There is no evidence of record of an unexpectedly superior result occurring due to the order of addition of the claimed components, thus the claimed order of addition is obvious (see MPEP 2144.04(I)(V)(C)). Therefore claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 are obvious over Zheng et al.
Claims 1, 4, 6-8, 10-13, 18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. as applied to claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 above, and further in view of Halder et al. (US PGPub No. 2011/0003816).
Zheng et al. render obvious the limitations of instant claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25, where the composition is a topical ophthalmic composition that can include a combination of povidone and hydroxypropylmethylcellulose. Relative proportions for combinations of these thickeners is not detailed.
Halder et al. teach a topical ophthalmic composition that includes thickeners to prolong residence time (see abstract and paragraphs 4-5). They detail the combination of polyvinyl pyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC), in particular, for their synergistic function in this role (see paragraph 13). The ratio of PVP to HPMC can vary and the greater the relative amount of HPMC, the higher the viscosity, for the tested varieties of each (see table 5). Discrete examples of 1:1, 2:8, and 9:10, respectively, are detailed.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a combination of PVP and HPMC at relative proportions as taught by Halder et al. for the thickener of Zheng et al. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The choice of a particular value amongst those taught would render those instantly claimed obvious as a matter of routine optimization. Therefore claims 1, 4, 6-8, 10-13, 18, 21, and 23-25 are obvious over Zheng et al. in view of Halder et al.
Claims 1-8, 10, 12-13, 18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. as applied to claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 above, and further in view of Zhang et al. (US PGPub No. 2017/0239273).
Zheng et al. render obvious the limitations of instant claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 where the composition provides lanosterol for treating cataracts. The instantly claimed concentration of lanosterol is not detailed.
Zhang et al. teach topical compositions of steroid compounds where lanosterol is embraced and exemplified for treating cataracts and other lens conditions (see paragraph 2-10, 25, 54, 62, and claim 30). They detail concentrations of the compound that range from 1 mg/ml to 500 mg/ml (0.001 mg/ml to 0.5 mg/ml; instant claims 2-3) (see paragraph 61).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the lanosterol at a proportion as detailed by Zhang et al. because they teach their concentrations as also being suitable for treating the lens. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The result is a range of proportions that overlap with those instantly claimed which renders the claimed range obvious (see MPEP 2144.05). These concentrations of lanosterol then yield ratios of surfactant to thickener to cosolvent to lanosterol that overlap with those of instant claim 5, due to the collection of proportions that result which is greater than 0 to 2 wt% : 0.2 to 6 wt% : 0.1 to 50 wt% : 0.0001 to 0.05 wt%. The overlap renders the instant range obvious (see MPEP 2144.05). Therefore claims 1-8, 10, 12-13, 18, 21, and 23-25 are obvious over Zheng et al. in view of Zhang et al.
Claims 1-8, 10-15, 18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. in view of Zhang et al. as applied to claims 1-8, 10, 12-13, 18, 21, and 23-25 above, and further in view of Halder et al.
Zheng et al. render obvious the limitations of instant claims 1-8, 10, 12-13, 18, 21, and 23-25 where the composition is a topical ophthalmic composition that can include a combination of povidone and hydroxypropylmethylcellulose. Relative proportions for combinations of these thickeners is not detailed.
Halder et al. teach a topical ophthalmic composition that includes thickeners to prolong residence time (see abstract and paragraphs 4-5). They detail the combination of PVP and HPMC, in particular, for their synergistic function in this role (see paragraph 13). The ratio of PVP to HPMC can vary and the greater the relative amount of HPMC, the higher the viscosity, for the tested varieties of each (see table 5). Discrete examples of 1:1, 2:8, and 9:10, respectively, are detailed (see instant claims 5 and 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a combination of PVP and HPMC at relative proportions as taught by Halder et al. for the thickener of Zheng et al. in view of Zhang et al. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The choice of a particular value amongst those taught would render those instantly claimed obvious as a matter of routine optimization. Therefore claims 1-8, 10-15, 18, 21, and 23-25 are obvious over Zheng et al. in view of Zhang et al. and Halder et al.
Claims 1, 4, 6-8, 10, 12-13, 18, and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. as applied to claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 above, and further in view of Ogidigben et al. (WO 2008027340).
Zheng et al. render obvious the limitations of instant claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25, where the composition is made by dispersing the lanosterol in a pharmaceutically acceptable carrier. The device employed to perform the dispersion is not detailed.
Ogidigben et al. teach the preparation of a topical ophthalmic composition where a drug active is dispersed in a pharmaceutically acceptable carrier (see abstract and example 2). Here the drug is combined with a pharmaceutically acceptable carrier and the mixture is homogenized with a homogenizer (see example 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ a homogenizer to mix the dispersion of Zheng et al. in light of Ogidigben et al. because it was detailed to be suitable to disperse a similar composition intended for a similar use. The modification is obvious as the application of the same technique to a similar product in order to yield the same improvement. Therefore claims 1, 4, 6-8, 10, 12-13, 18, and 21-25 are obvious over Zheng et al. in view of Ogidigben et al.
Claims 1-10, 12-13, 18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. as applied to claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25 above, and further in view of Zheng et al. (US PGPub No. 2019/0192427 – henceforth Zheng B).
Zheng et al. render obvious the limitations of instant claims 1, 4, 6-8, 10, 12-13, 18, 21, and 23-25, where lanosterol is present for cataract treatment. They additionally envision the inclusion of a second drug active that is an azole (see paragraph 32). The presence of 25-hydroxycholesterol is not detailed.
Zheng B teaches a composition, much like that of Zheng et al., to teach cataracts (see abstract). They detail pairing a steroid compound with an azole compound for superior performance over the steroid alone (see example 4). The steroid compound is envisioned as selected from a short listing that includes lanosterol and 25-hydroxycholesterol and their combination (see paragraphs 116-120 and 122-126; instant claim 9). As the second drug of Zheng B, the steroid is envisioned present at 0.01 to 20 wt% (0.1 to 2000 mg/ml) (see paragraph 120).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make an azole containing embodiment of Zheng et al. where 25-hydroxycholesterol is included along with or in place of the lanosterol. This modification would have been obvious in light of Zheng B as the application of the same technique to a similar product in order to yield the same improvement and as the simple substitution of one known element for another in order to yield a predictable outcome. The result is a range of proportions that overlap with those instantly claimed which renders the claimed range obvious (see MPEP 2144.05; instant claims 2-5). Therefore claims 1-10, 12-13, 18, 21, and 23-25 are obvious over Zheng et al. in view of Zheng B.
Claims 1-13, 16-18, 21, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. in view of Zheng B as applied to claims 1-10, 12-13, 18, 21, and 23-25 above, and further in view of Halder et al.
Zheng et al. in view of Zheng B render obvious the limitations of instant claims 1-10, 12-13, 18, 21, and 23-25, where the composition is a topical ophthalmic composition that can include a combination of povidone and hydroxypropylmethylcellulose. Relative proportions for combinations of these thickeners is not detailed.
Halder et al. teach a topical ophthalmic composition that includes thickeners to prolong residence time (see abstract and paragraphs 4-5). They detail the combination of PVP and HPMC, in particular, for their synergistic function in this role (see paragraph 13). The ratio of PVP to HPMC can vary and the greater the relative amount of HPMC, the higher the viscosity, for the tested varieties of each (see table 5). Discrete examples of 1:1, 2:8, and 9:10, respectively, are detailed (see instant claim 16).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a combination of PVP and HPMC at relative proportions as taught by Halder et al. for the thickener of Zheng et al. in view of Zheng B et al. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The choice of a particular value amongst those taught would render those instantly claimed obvious as a matter of routine optimization. Therefore claims 1-13, 16-18, 21, and 23-25 are obvious over Zheng et al. in view of Zheng B and Halder et al.
Claims 11-5, 12-13, 19-20, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US PGPub No. 2013/0150335 – henceforth Liu B).
Liu B teaches submicron emulsions of paclitaxel complexed with a steroid, where the molar ratio of paclitaxel to steroid is 1:0.2 to 4 (see abstract). They teach the emulsion (self-assembled nanoparticles) with a diameter of less than 600 nm (spherical particles) and exemplify sizes ranging from about 120 to about 520 nm (see paragraph 8 and table 8; instant claims 19-20). Submicron emulsion 2 employes a 1:1 molar ratio of the steroid to paclitaxel and includes 145 mg of the combination with water, 2 g lecithin (surfactant), 1 g poloxamer (thickener), and 5 g glycerol (cosolvent) (see table at paragraph 101; instant claims 1 and 12-13). Liu B teaches lanosterol as an envisioned steroid (see paragraph 16).
While a full example for each embodiment that follows from the teachings of Liu et al. is not detailed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an embodiment of Liu et al. where lanosterol is the steroid, for example, by modifying their submicron emulsion 2. The 1:1 molar ratio of paclitaxel to lanosterol corresponds to a 2:1 mass ratio (as calculated by the examiner based on a 426 g/mol lanosterol molar mass and 853 g/mol paclitaxel molar mass). The composition would then provide 200 ml with 2000 mg surfactant, 1000 mg thickener, 5000 mg cosolvent, and 48 mg lanosterol which is a 50:41:104:1 ratio with 0.24 mg/ml lanosterol (as calculated by the examiner; instant claims 1-5). Claims 23-25 recite an intended use for the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Here the composition of Liu et al. is capable of performing the recited use since it has the claimed active at the claimed concentration, therefore it meets the intended use limitations. Thus claims 1-5, 12-13, 19-20, and 23-25 are obvious over Liu et al.
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/Examiner, Art Unit 1615