The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of Claims
Claims 1-14 are pending and are currently under examination.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
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 1-6 and 12-14 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Gil (WO 2010/093930) in view of Chow et al. (WO1999/28300).
Gil teaches a pharmaceutical composition comprising (3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol and methods of using the composition to treat chronic pain (abstract). Also, the reference discloses that (3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol occurs as two enantiomers: (R)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol (Compound II) and (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol (Compound III), which are formed by the in vivo hydroxylation of medetomidine (5-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole) (p1, line 20-p2, line 11). Gil further teaches metabolites of medetomidine and dexmedetomidine and their synthesis are known (p2, line 17-p3, line 7). Gil discloses agonist and antagonist activities of Compounds, I, II, and III at the alpha-1A, alpha-1B, alpha-2A, alpha-2B, and alpha-2C adrenergic receptors (data in the first line in each column shows agonism):
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(p20, line 3-12 and Table 2). Gil teaches that the compounds of the invention may be used to treat chronic pain without sedation and the Compounds of the invention may be administered topically (p3, lines 5-7 and p15, lines 10-12). In addition, Gil teaches that the compounds of the invention may be administered at pharmaceutically effective doses and the actual amount of the compound to be administered in any given case will be determined by a physician taking into account the relevant circumstances, such as the severity of the pain, the age and weight of the patient, the patient's general physical condition, the cause of the pain, and the route of administration (p16, lines 11-21).
The reference differs from the instant claims insofar as it does not specifically teach the use of (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol (Compound III) for lowering intraocular pressure. Also, it does not specifically teach the claimed weight percentage.
Chow et al. teach that substituted imidazole derivatives having alpha-2B or alpha-2B/ alpha-2C adrenoceptor agonist activities are useful for treating glaucoma or elevated intraocular pressure as well as pain with substantially reduced cardiovascular or sedative effects wherein the imidazole derivative is at least ten times more potent at alpha-2B or alpha-2C adrenoceptor subtype than at the alpha-2A adrenoceptor receptor (abstract, p68, table 1, claims 1, 72 and 74). In particular, Chow et al. disclose compound structurally very close to the claimed compound is effective for reducing ocular pressure without sedation (see p68, Table 1, compound C-8 and p85, table 2). Chow et al. further teach that the pharmaceutical composition having an adrenergic compound are useful for treating glaucoma and reducing intraocular pressure as well as chronic pain (p1, lines 19-26, p2, lines 19-26, and claim 79). Chow et al. further teach that the compound 0.01% to 3% by weight of the compound is administered topically to the host mammal daily or twice daily doses (claim 76). Chow et al. further teach that for topical administration, any common topical formulation such as solution, suspension, gel, ointment, or salve and the like may be applied to the eye in glaucoma and preparation of such topical formulations are well described in the art of pharmaceutical formulations as exemplified, for example, by Remington’s Pharmaceutical Science, Ed. 17 (p4, lines 19-25).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol taught by Gil for lowering intraocular pressure as taught by Chow et al. because of the following reasons. From the teachings of Gil, one of ordinary skill in the art would have recognized that (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol is more potent (e.g., at least ten times) at alpha-2B or alpha-2C adrenoceptor subtype than at the alpha-2A adrenoceptor receptor (see Table 2) and can be used for treating chronic pain without sedation. Chow et al. teach, motivate, and suggest the use of structurally similar imidazole derivatives having greater agonistic activity at alpha-2B or alpha-2B/ alpha-2C adrenoceptor than at alpha-2A adrenoceptor for the treatment of glaucoma or elevated intraocular pressure as well as chronic pain with a minimum of sedation or other side effects. Therefore, one of ordinary skill in the art at the time the invention was made would have been motivated to use (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol for treating elevated intraocular pressure and glaucoma as well as chronic pain on the reasonable expectation that (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol taught by Gil would be effective for lowering intraocular pressure similarly to the imidazole derivatives taught by Chow et al. without sedation effects.
As claims 4-6, Chow et al. teach ranges of concentrations of the active ingredient that overlap with the claimed concentrations as stated above. Accordingly, at the time of the instant invention, it would have been obvious to a person of ordinary skill in the art to vary and/or optimize the amount of ingredients provided in the composition, according to the guidance provided by Chow et al. in order to provide a composition having the desired properties such as the desired ratios, concentrations, percentages, etc. It is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In addition, it has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
As to the recitations: "having an intraocular pressure less than the baseline intraocular pressure for at least 10 or 12 hours in claims 2-3 and maintaining an intraocular pressure less than the baseline intraocular pressure throughout the day in claim 12, those are intended results of the active method step (i.e., administering (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol to the affected eye), and as such are non-limiting since such language does not result in manipulative difference in steps of claims. The references in combination teach, suggest or motivate the same method step as instantly claimed (i.e. topically administering (S)-(3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol to the affected eye), thus the method necessarily performs the functions as recited in claims when the composition is topically administered to a subject as taught by the prior art in combination. “[N]ewly discovered results of known processes directed to the same purpose are not patentable." Bristol-Myers Squibb, 246 F.3d at 1376. Also, see In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980) (a case indicating that the burden of proof can be shifted to the applicant to show that the subject matter of the prior art does not possess the characteristic relied on whether the rejection is based on inherency under 35 U.S.C.102 or obviousness under 35 U.S.C. 103).
As to claim 14, the printed matter on a label or package insert of a kit or container does not lend patentable weight as a limitation of the claimed product, composition, or article of manufacture since there is no functional relationship between the label or package insert of a kit and the product, composition, or article of manufacture of a kit or container. See In re Haller 73 USPQ 403 (CCPA 1947), where it is held that application of printed matter to old article cannot render the article patentable. In the opinion text of In re Haller, it is stated that: Whether the statement of intended use appears merely in the claim or in label on the product is immaterial so far as the question of patentability is concerned. In the instant case, the claim is drawn to an old article or composition, which further comprises labeling instructions since the prior art teaches a pharmaceutical composition comprising an effective amount of the same compound as claimed. The intended use, which is recited on the label or package of the insert, lacks a function relationship because the insert or label does not physically or chemically affect the chemical nature within the article of manufacture, and furthermore, the old article or old composition of the kit can still be used by the skilled artisan for other purposes. Therefore, the old article or composition which are comprised with the claimed compound are unpatentable over the prior art, because they function equally effectively with or without the labeling, and accordingly no functional relationship exists between the instructions for use and the composition. Thus, the claim is addressed as being drawn to an article comprising an old composition and a package insert, the instructions on the insert bearing no patentable weight with regard to double patenting, 102 and 103 rejections. See MPEP § 2112.01: Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) (Claim at issue was a kit requiring instructions and a buffer agent. The Federal Circuit held that the claim was anticipated by a prior art reference that taught a kit that included instructions and a buffer agent, even though the content of the instructions differed, explaining "[i]f we were to adopt [applicant’s] position, anyone could continue patenting a product indefinitely provided that they add a new instruction sheet to the product.").
From the teachings of the references in combination, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 7-11 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Gil (WO 2010/093930) in view of Chow et al. (WO1999/28300) in further view of US 2008/0103153.
Gil and Chow et al. as applied supra are herein applied for the same teachings in their entirety.
The prior art does not specifically teach a preservative, a co-solvent, and a viscosity building agent and their concentrations. However, it was well known in the art to incorporate those excipients for ophthalmic preparations. Chow et al. already teaches that for topical administration, any common topical formulation such as solution, suspension, gel, ointment, or salve and the like may be applied to the eye in glaucoma and preparation of such topical formulations are well described in the art of pharmaceutical formulations. As evidence by US 2008/0103153, which teaches ophthalmic compositions for treating glaucoma and elevated intraocular pressure (abstract), ophthalmic products are typically packaged in multidose form, and preservatives are thus required to prevent microbial contamination during use, and typically such preservatives are employed at a level of from 0.004% to 0.02% ([0013]). Also, US 2008/0103153 teaches that a surfactant or other appropriate co-solvents such as polysorbate 20, 60, and 80, Pluronic F68, F-84 and P-103, cyclodextrin, or other agents known to those skilled in the art may be included to enhance the solubility of the components and typically such co-solvents are employed at a level of from 0.01% to 2% by weight ([0014]). In addition, US 2008/0103153 teaches that viscosity agents are included to increase ocular absorption of the active compound, to decrease variability in dispensing the formulation, to decrease physical separation of components of a suspension or emulsion of the formulation and/or to otherwise improve the ophthalmic formulation and such agents are at a level of from 0.01% to 2% by weight ([0015]). Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was to incorporate those known excipients in amounts typically employed into topical compositions for ophthalmic use. Generally, it is prima facie obvious to select a known material for incorporation into a composition based on its recognized suitability for its intended use. See MPEP 2144.07.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611
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