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 .
Receipt is acknowledged of Remarks filed on 12/03/25 and a Terminal Disclaimer filed on 12/16/2025. No claims have been amended, cancelled or added. Accordingly, claims 1-2, 5-16 remain pending and under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Terminal Disclaimer
The terminal disclaimer filed on 12/16/25 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application Nos. 16810095 and 17699405 has been reviewed and is accepted. The terminal disclaimer has been recorded.
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 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 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 1-2, 5-12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Graham et al (US 20140249153) in view of Alm (Latanoprost in the treatment of glaucoma) and Horn et al (US 20150290126).
Graham et al teach ophthalmic compositions comprising combinations of brimonidine and bimatoprost useful for lowering intraocular pressure in a patient and for the treatment of glaucoma (See Abstract, [0024], [0029]-[0043]).
Graham et al teach and claim a method of lowering intraocular pressure or treating glaucoma in a human patient comprising administering the composition of embodiment 3, which is a composition comprising bimatoprost in the concentration range of 0.001-0.03% w/w and the brimonidine in the concentration range of 0.005%-0.2% w/w (See [0018]-[0022]).
Graham et al then states that “the method of embodiments 22-24 wherein the method is effective in treating glaucoma and lower ocular hypertension” (See [0043]-[0044]). That is, the composition of embodiment 22 is related to the composition of embodiment 20 wherein the concentration of brimonidine tartrate is 0.005%-0.2% w/w.
Typical concentration of brimonidine is exemplified as 0.01% in the ophthalmic product (See Table 1).
As evidenced by at least the Specification at [0004], bimatoprost is a known glaucoma drug.
Graham et al lack a specific disclosure on combining brimonidine with latanoprost. This is obvious over Alm. Graham et al also lack a disclosure on the said compositions comprising a nonionic surfactant or a sorbate. This is known in the art as shown by Horn et al.
Alm teaches that prostaglandins are approved by the European Glaucoma Society guidelines as firstline treatment for glaucoma including latanoprost, an ester prodrug of prostaglandin (PG) F2α, which was the first of the currently available topical PGF2α analogs to be launched for glaucoma or ocular hypertension and which still accounts for the majority of prescriptions. Latanoprost (0.005%) has been very well studied in clinical trials and meta-analyses that show it to be generally as effective as the other PG analogs (bimatoprost, travoprost, and tafluprost) and more effective than timolol, dorzolamide, and brimonidine. Latanoprost has good short- and long-term safety and tolerability profiles. Latanoprost is significantly better tolerated than either bimatoprost or travoprost (See abstract).
It is disclosed that latanoprost (0.005%) was launched in 1996 and was the first of the currently available topical PGF2α analogs on the market for glaucoma treatment (See page 1968, 2nd col). The considerable amount of data available indicates that latanoprost is equally as effective as bimatoprost (See page 1969, 2nd col). Specific studies strongly suggest that compliance and persistence with latanoprost is superior to that with other glaucoma treatments (See page 1981, 2nd col).
Horn et al teach compositions and methods for the treatment of presbyopia (See abstract and [0011]). In certain embodiments, the said ophthalmological composition for the treatment of presbyopia comprises aceclidine and a selective a-2 adrenergic receptor agonist (See [0018]).
In a more preferred embodiment, the selective a-2 agonist is brimonidine, and is present at a concentration
Horn et al disclose that “Comfort, safety, and efficacy of a preferred embodiment of an ophthalmological composition … results from the presence of a nonionic surfactant, such as cyclodextrin alpha, beta, or gamma chains, poloxamer 407; a viscosity enhancing agent, such as carboxymethyl cellulose ("CMC"); a tonicity adjustor, such as sodium chloride; a preservative, such as benzalkonium chloride and a pH from about 5.0 to about 8.0. Further, an increase in the concentration of the viscosity agent and the electrolyte may result in reduced redness. Specifically, increasing CMC from 0.50% to 0.75% w/v (preferably 0.80% w/v) and sodium chloride from 0.25% to 0.50% w/v results in reduced redness” (See [0067]).
It is also disclosed that the formulations may contain a viscosity enhancers including carboxymethyl cellulose, at a concentration from about 0.5% to about 6.0% w/v, preferably from about 0.09% to about 1.0% w/v (See 0099]-[0100]).
The said formulations may also comprise a nonionic surfactant such as a polysorbate, or polysorbate 80 present at a concentration from about 1 to about 15% w/v (See [0034], [0095] and [0097]). Horn et al disclose that a pH less than physiologic pH is found to enhance the whitening effect for brimonidine (See [0061] and [0111]).
The combination of aceclidine and a low concentration of a selective α-2 adrenergic receptor agonist such as brimonidine, allows for the desired miotic effect with diminished or no redness. The use of low concentrations of brimonidine results in substantial reduction of hyperemia with greatly reduced risk of rebound hyperemia that is found in concentrations of about 0.06% w/v or more (See [0063]). The addition of 0.03% w/v brimonidine reduced redness of the eye after instillation of the topical formulation (See [0238]).
Various buffers and means for adjusting pH can be used to prepare said ophthalmological compositions. Such buffers include, citrate buffers, phosphate buffers and borate buffers, added at preferably of 1 to 10 mM concentration, and more preferably about 5 mM. In a preferred embodiment the pH is from about 4.0 to about 8.0 (See [0121]).
It would have been obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Horn et al and Alm with that of Graham et al to arrive at the instant invention. One of ordinary skill in the art would have been motivated to do so because both Graham et al and Horn et al teach ophthalmic formulations comprising two or more active agents for their given benefits. The active agents and their concentration ranges as well as the suitable excipients are disclosed and one of ordinary skill in the art would have been motivated to combine the teachings and take advantage of the combined active agents in ophthalmic formulations. It is known in the art that multiple active agents in the same formulations treats multiple disorders with one treatment. Alm also provides studies and evidence that latanoprost is as effective as bimatoprost in treating glaucoma. Thus, one of ordinary skill in the art would have been motivated to have selected latanoprost of Alm as the therapeutic agent to combine with brimonidine of Graham et al or Horn et al to treat glaucoma. It further would have been obvious to one of ordinary skill in the art to recommend the ophthalmic formulations of Graham et al and Alm comprising brimonidine and bimatoprost or latanoprost as the active agents for reducing redness or increasing eye whitening based on the disclosures of Horn et al.
Also, with regard to the concentration ranges the courts have held that “Where 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, 105 USPQ 233 (CCPA 1955). The references provide the same concentrations or sufficient guidance to one of ordinary skill in the art to determine the desired amounts.
Claims 1-2, 5-12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Horn (US 20100029662) in view of Alm (Latanoprost in the treatment of glaucoma) and Horn et al (US 20150290126).
Horn ‘662 teach compositions for inducing vasoconstriction. The compositions comprise highly selective alpha-2 adrenergic receptor agonists, at low concentrations, such as below 0.05% weight by volume. The compositions preferably comprise brimonidine (See abstract).
The said selective a-2 adrenergic receptor agonist is selected from the group consisting of apraclonidine, mivazerol, clonidine, brimonidine, alpha methyl dopa, guanfacine, dexemeditomidine, (+)-(S)-4-[1-(2,3-dimethyl-phenyl)-ethyl]-1,3-dihydro-imidazole-2-thione, 1-[(imidazolidin-2-yl)imino]indazole, and mixtures of these compounds (See [0044] and claim 4).
Horn teach that “In another embodiment, the invention relates to a surprising finding that an aqueous composition comprising a selective a-2 adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, can be used for the prevention or treatment of a disease or a condition by administering said aqueous composition to a patient in need thereof, wherein the concentration of said agonist in said aqueous composition is substantially lower than the concentration of said agonist normally used in the treatment of glaucoma (See [0038]).
Horn discloses that in a preferred embodiment, the composition comprises brimonidine at a concentration between about 0.001% and about 0.025% weight by volume (w/v) (See [0045]).
In another preferred embodiment, the method comprises administering to a patient having an ocular condition a composition comprising brimonidine, wherein said brimonidine concentration is between about 0.001% and about 0.025% w/v (See [0057]). Said ocular conditions include glaucoma, elevated intraocular pressure; excessive redness of the eye, etc, (See [0110]).
Horn further discloses that the said compositions are topical compositions, including compositions formulated for treating and/or preventing an ocular condition. The said topical compositions, which are ophthalmic compositions include ocular drops, ocular ointments, gels and creams. The said compositions may also include additional non-therapeutic components, which include buffers, preservatives, delivery vehicles, tonicity adjustors, pH adjustors, antioxidants, and water. Such components include polyvinyl alcohol, povidone, poloxamers, carboxymethyl cellulose, potassium chloride, mannitol, sodium chloride, and purified water. Various buffers and means for adjusting pH can be used including citrate buffers, phosphate buffers and borate buffers (See [0149]-[0155]).
Horn ‘662 is silent with regard to combining brimonidine with latanoprost. This is obvious over Alm. Horn ‘662 also lacks a disclosure on the said compositions comprising the nonionic surfactant, sorbate. This is known in the art as shown by Horn et al.
The teachings of Alm and Horn et al ‘126 are delineated above and incorporated herein.
It would have been obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Horn et al and Alm with that of Horn ‘662 to arrive at the instant invention. One of ordinary skill in the art would have been motivated to do so because both Horn ‘662 and Horn et al teach ophthalmic formulations comprising two or more active agents for their given benefits. The said compositions comprise brimonidine at low concentrations and disclosed as being surprisingly effective in treating ocular conditions including glaucoma and IOP. The active agents and their concentration ranges as well as the suitable excipients are disclosed and one of ordinary skill in the art would have been motivated to combine the teachings and take advantage of the combined active agents in ophthalmic formulations. It is known in the art that multiple active agents in the same formulations treats multiple disorders with one treatment. Alm also provides studies and evidence that latanoprost is as effective as bimatoprost in treating glaucoma. Thus, one of ordinary skill in the art would have been motivated to have selected latanoprost of Alm as the therapeutic agent to combine with brimonidine of Horn ‘662 or Horn et al to treat glaucoma. It further would have been obvious to one of ordinary skill in the art to recommend the ophthalmic formulations of Horn ‘662 and Alm comprising brimonidine and bimatoprost or latanoprost as the active agents for reducing redness or increasing eye whitening based on the disclosures of Horn et al.
Claims 1-2, 5-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gore et al (US 20130157963).
Gore et al teach ophthalmic compositions for treating a disease of the eye comprising one or more therapeutically active agents such as an alpha-adrenergic antagonist, a steroid, a prostaglandin, an alpha agonist, an antibiotic, an anti-infective agent, an anti-inflammatory, a beta blocker, or a combination thereof. The said therapeutically active agent comprises prednisolone, bimatoprost, latanoprost, brimonidine, ketorolac, a steroid, timolol, or a combination thereof. The said composition may be a solution (See [0012]-[0015] and [0046]).
Gore et al disclose that the said composition may comprise an osmolality agent such as mannitol, sodium chloride or a combination thereof, a buffer such as a borate buffer (See [0018]-[0021], [0047]-[0049] and [0054]). The amount of osmolality agent may be from 0.0001% to 5% (See [0055]).
Gore et al especially disclose a method of treating a disease of the eye wherein bimatoprost and brimonidine are the active agents (See [0003], [0028]-[0029]).
The said ophthalmic formulations may comprise the buffer at a concentration of from 1 to about 100 mM (See [0049]), and also comprise a surfactant such as a sorbitan derivative, polysorbate 80, etc. The amount of surfactant is typically from about 0.001 to about 5% (See [0051]). The said formulations may comprise a co-solubilizing agent such as carboxymethyl cellulose (See [0053]), a chelating agent such as edetate disodium and a preservative such as potassium sorbate in an amount of from 0.1 to about 4% (See [0057] and [0062]).
The ophthalmic disease to be treated may be neovasular glaucoma (See [0073]).
Typical concentration of brimonidine is from 0.001% to 1% and of latanoprost from 0.001% to 0.1% in the ophthalmic product (See Table 8).
Gore et al teach that the formulation may comprise a prostaglandin such as bimatoprost or latanoprost (See Table 8). In Table 15, Gore et al disclose a formulation comprising EDTA at a range of from 0-0.05%, mannitol at 0-5% and wherein the pH is from 5-8, typically 7.4.
Gore et al do not exemplify a formulation comprising the claimed components in the claimed ranges, but teach each and every element and provide sufficient guidance to one of ordinary skill in the art to make and use the claimed invention.
Thus, it would have been obvious to a person of ordinary skilled in the art at the time the invention was made to have followed the teachings of Gore et al to arrive at the instant invention. Gore et al teach ophthalmic compositions for treating diseases of the ye such as glaucoma and wherein the composition may comprise two or more active agents for the desired treatment. It is disclosed that the said compositions may comprise one of more active agents selected from prostaglandins and alpha agonists. In one embodiment, Gore et al disclose a method of treating a disease of the eye by a combination of brimonidine and bimatoprost. It is also disclosed that prostaglandins include bimatoprost and latanoprost. As such one of ordinary skill in the art would have been motivated to have selected latanoprost as the prostaglandine as they are disclosed as equivalent and alternative species with a reasonable expectation of success.
Additionally, Gore et al disclose a number of suitable e excipients and additives to prepare the said ophthalmic formulation and provides suggestions to their suitable concentration ranges. As such one of ordinary skill in the art is more than capable of selecting the said additives in their desired range with a reasonable e expectation of success.
With regard to the concentration ranges, it is considered that one of ordinary skill in the art is capable of optimization of ranges. Courts have held that “Where 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, 105 USPQ 233 (CCPA 1955).
It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to provide a composition comprising brimonidine and latanoprost and the claimed additives at desired concentration ranges for treating eye diseases such as glaucoma. If not expressly taught, the adjustment of particular conventional working conditions is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of the reference, 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 was 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 1-2, 5-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chapin et al (US 20100311688) in view of Horn et al (US 20140038974) and Gore et al (US 20130157963).
Chapin et al teach compositions for treating signs and symptoms associated with dry eye and/or ocular irritation, and methods of use thereof. Such compositions are provided in novel ophthalmic formulations that are comfortable upon instillation in the eye (See abstract).
It is disclosed that dry eye can cause keratitis, conjunctival and corneal staining, redness, blurry vision, increased conjunctival redness, ocular dryness, ocular grittiness, ocular burning, ocular itching due to a combination of ocular allergy and dry eye symptoms, etc, (See [0004]).
Chapin et al disclose an aqueous ophthalmic solution containing a viscosity enhancing agent or combination of viscosity enhancing agents, a tonicity agent or combination of tonicity agents, and a buffer or combination of buffers. The viscosity enhancing agent may be hydroxypropyl methylcellulose, carboxymethyl cellulose, etc, present in an amount of from 0.5 to 2% (See [0039] and [0040]-[0041]). The formulations also comprise sorbate (See [0010]-[0012]).
The said buffering components are present from 0.05% to 2.5% (w/v) or from 0.1% to 1.5% (w/v) and comprise of borate buffers, phosphate buffers, citrate buffers, and combinations and mixtures thereof (See [0047]-[0048]).
In a combined boric/citrate buffer system, the solution comprises about 0.05 to 2.5% (w/v) of a citric acid or its salt and 0.1 to 5.0% (w/v) of boric acid or its salt. The citrate buffer is used (in total) at a concentration of 0.004 to 0.2 M (Molar), preferably 0.04 to 0.1 M (See [0052]). The pH of the aqueous ophthalmic solution is at or near physiological pH, i.e. between about 6.8 to about 7.7 (See [0054]). The said viscosity enhancing agent may be polysorbate 80, CMC, etc, or combinations thereof present at a concentration range from about 0.2% to about 10% w/v (See [0039]-[0040]). The said formulations may also comprise a solubilizer such as polysorbate 20 or polysorbate 80 (See [0070]).
Chapin et al disclose that the said aqueous ophthalmic formulations are suitable for use as artificial tear products to relieve symptoms of dry eye and as a vehicle for an ophthalmic drug. Ophthalmic drugs suitable for use in the said formulations include antiglaucoma agents, such as brimonidine and a prostagalndine such as latanoprost, etc, and combinations thereof (See [0060]). The total concentration of drug will generally be about 5% or less (See [0064]).
Chapin et al lack a specific disclosure on the concentration range of brimonidine and latanoprost, potassium sorbate, EDTA in the formulation. These are known in the art as shown by Horn et al ‘974 and Gore et al.
Horn et al ‘974 teach compositions and methods for whitening of eyes and/or reducing redness of eyes. The compositions preferably include brimonidine (See abstract). The said compositions and methods may be used to whiten healthy eyes and/or to reduce hyperemia in an eye which is due to a disease or a condition (See [0010]).
Disclosed is a method of increasing whiteness of an eye comprising administering to a subject in need thereof a composition comprising a selective α-2 adrenergic receptor agonist including brimonidine, present at a concentration from about 0.001% to about 0.06% weight by volume (See [0015]-[0016] and [0081]).
Horn et al disclose a patient with glaucoma who was receiving LumiganRTM (bimatoprost ophthalmic solution 0.03%), treatment, was administered 0.025% brimonidine to reduce redness and increase whiteness of an eye. This Example demonstrates that 0.025% brimonidine resulted in significant reduction of redness and increase of whiteness of an eye (See [0121]-[0122]).
Horn et al state that some compounds having selective α-2 agonist activity, including brimonidine has been used for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension (See [0005]).
The pH of the said compositions is less than about 8.0, preferably, from about 5.5 to about 8.0, more preferably from about 6.0 to about 8.0 (See [0095]). The pH is adjusted by a buffer system such as borate buffer (See [0107]).
Horn et al disclose an aqueous composition for use in increasing whiteness of an eye, comprising from about 0.01% to about 0.025% weight by volume of brimonidine, wherein pH of said composition is from about 7.0 to about 8.0, and wherein said composition is formulated for a topical administration (See [0090]).
Gore et al’s teaching are delineated above and incorporated herein. Specifically, Gore et al disclose that typical concentration of latanoprost in an ophthalmic product is from 0.001 to 0.1% (See at least Table 8).
It would have been obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Horn et al and Gore et al with that of Chapin et al to arrive at the instant invention. One of ordinary skill in the art would have been motivated to do so because Chapin et al, Gore et al and Horn et al teach ophthalmic formulations comprising two or more active agents for their given benefits. The active agents and their concentration ranges as well as the suitable excipients are disclosed and one of ordinary skill in the art would have been motivated to combine the teachings and take advantage of the combined active agents in ophthalmic formulations. It is known in the art that multiple active agents in the same formulations treats multiple disorders with one treatment. It further would have been obvious to one of ordinary skill in the art to recommend the ophthalmic formulations of Chapin et al comprising brimonidine as one of the active agents for reducing redness or increasing eye whitening based on the disclosures of Horn et al.
One of ordinary skill in the art given the teaching of Chapin et al in combining latanoprost with brimonidine would have been motivated to look in the art for suggestion on concentration levels as disclosed by Gore et al.
Also, with regard to the concentration ranges the courts have held that “Where 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, 105 USPQ 233 (CCPA 1955). The references provide the same concentrations or sufficient guidance to one of ordinary skill in the art to determine the desired amounts.
Response to Arguments
Applicant's arguments filed 12/03/25 have been fully considered but they are not persuasive.
Applicant’s first argument is regarding the rejection of claims over Graham et al, Alm et al and Horn et al, and reads “Graham teaches that 0.01% brimonidine is ineffective alone. See Example 1…. The only amount of brimonidine that is taught as effective by Graham is 0.1% brimonidine in combination with 0.01% bimatoprost. See Example 1. A skilled artisan would thus understand that the use of 0.01% w/v brimonidine to treat glaucoma is ineffective. This is evidence that the teaching in Graham of 0.05-0.2% brimonidine, whether or not it is combined with a 2nd glaucoma drug, is incorrect. A skilled artisan, in light of the entire scope of the prior art, would understand that Graham does not teach that brimonidine is effective at the claimed concentration range”. Applicant argues that Horn ‘126 would not motivate one of ordinary skill in the art to lower the amount of brimonidine to treat glaucoma (See Remarks, pages 4-5).
The above argument is not persuasive. Firstly, Graham discloses that a combination of two agents, i.e. brimonidine and bimatoprost is more effective than monotherapy. Example 1 is related to monotherapy of each compound. Secondly, in Example 3, Graham et al disclose that formulation 3, which comprises brimonidine and bimatoprost (same dose as in Example 1) were therapeutically effective in treating IOP and open-angle glaucoma. Thirdly, Graham et al’s disclosure is regarding a composition and method of treating glaucoma wherein the composition comprises bimatoprost in the concentration range of 0.001-0.03% w/w and the brimonidine in the concentration range of 0.005-0.2% w/w. Graham et al then states that “the method of embodiments 22-24 wherein the method is effective in treating glaucoma and lower ocular hypertension” (See [0018]-[0022] and [0043]-[0044]). The composition of embodiment 22 is related to the composition of embodiment 20 wherein the concentration of brimonidine tartrate is 0.005-0.2% w/w. Thus, while the exemplified dose appears to be 0.1%, Graham et al clearly envisioned and disclosed a concentration range of 0.005-0.2% as being effective in treating glaucoma and elevated ocular pressure. Additionally, Horn et al disclose an ophthalmological formulation comprising brimonidine at a concentration of 0.025% to 0.065% w/v, more preferably from 0.03% to 0.035% w/v (See [0107]). As such one of ordinary skill in the art having possession of both references would have easily realized that a low concentration of brimonidine is effective in an ophthalmological composition. Furthermore, both Graham et al and Horn et al teach their formulation as effective in treating redness or increasing whitening. Accordingly, providing further motivation to one of ordinary skill in the art.
Regarding the rejection of claims over Gore et al, Applicant argues that “Gore is cited as teaching from 0.001% to 0.1% brimonidine and 0.001% to 0.1% latanoprost. This is not “sufficient guidance....to make and use the claimed invention.” …… The only guidance provided by Gore as to what concentrations from this broad range might be useful is the example of brimonidine is 0.1%. Further, at the time of filing the present application, brimonidine was used to treat glaucoma at a concentration of 0.1% (Alphagan®). A skilled artisan would not have been motivated to use a much lower concentration of brimonidine as claimed for a combination with latanoprost.” (See Remarks, page 5).
The above arguments are also not found persuasive. Firstly, it is noted that a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). While Gore et al do not teach the narrower ranges, they do disclose the claimed range. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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”. Additionally, MPEP states that - Regarding the claimed ranges, it is considered that where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists-See MPEP § 2144.05 [R-5]. Thus, Gore et al’s disclosure of the claimed concentration ranges is sufficient to make the claimed composition and method obvious to one of ordinary skill in the art.
Also, regarding the argument of Gore et al’s examples being drawn to a concentration of 0.1% brimonidine, the courts have held that “It is well-established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the submitted knowledge in the art, to a person of ordinary skill in the art”. In re Boe, 355, F.2d 961, 148 USPQ 510, 510 (CCPA 1966).
With respect to the rejection of claims over Chapin et al, Gore et al and Horn et al, Applicant argues that “Chapin is directed to treating dry eye, while Horn is directed to cosmetic eye whitening. These two references are not within the same field. Thus, a skilled artisan would not combine Chapin with Horn to arrive at the instant invention directed to compositions and methods for the treatment of glaucoma. Chapin further teaches that redness is a symptom of dry eye. However, cosmetic eye whitening is whitening beyond redness.” (See Remarks, page 6).
The above argument is also not found persuasive. Again, the examined claims are drawn to an ophthalmological formulation comprising brimonidine and latanoprost at given concentration ranges. The claims are not limited or affected by treatment of glaucoma. Chapin et al teach that the formulations comprising glaucoma agents including brimonidine and latanoprost can treat dry eye, redness, blurry vision, increased conjunctival redness, ocular dryness, ocular grittiness, ocular burning, ocular itching due to a combination of ocular allergy and dry eye. Horn et al teach treating redness with a formulation comprising brimonidine, present at a concentration from about 0.001% to about 0.06% weight by volume (See [0015]-[0016] and [0081]). Gore et al teach that typical concentration of latanoprost in an ophthalmic product is from 0.001 to 0.1% (See at least Table 8).
Accordingly, not only one of ordinary skill in the art has been given motivation to incorporate the concentration ranges of brimonidine and latanoprost from Horn et al and Gore et al’s disclosures into the formulations of Chapin et al, but they would expect a reasonable expectation of success.
Additionally, the argument of treating glaucoma is not commensurate with the scope of claims 1-2 and 5-15, which are drawn to a composition comprising brimonidine and latanoprost at given concentration ranges. The term “for the treatment of glaucoma” is an intended use limitation that does not in any way materially affect the structure of the claimed composition. Secondly, while the references have not exemplified a composition comprising 0.059% or less of brimonidine to treat glaucoma, they do teach the compositions comprising brimonidine at low doses and teach that brimonidine and latanoprost are effective in treating glaucoma.
Claims 1-2, 5-16 remain rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached on M-F, 7-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X. Liu can be reached on 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
Prosecution Insights