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 .
Change of Examiner
Applicant is advised that the Examiner assigned to the prosecution of the instant application has changed.
Status of the Claims
This action is in response to papers filed 09/11/2025 in which claims 1-11 were amended. All the amendments have been thoroughly reviewed and entered.
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn.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.
Claim Objection
Claim 5 is objected for following reason: 1) “a viscosity agent, wherein viscosity agent” should be replaced to “the viscosity agent, wherein the viscosity agent” to properly refer back to a viscosity agent in claim 1.
Claim Rejections - 35 USC § 112
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 1-11 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 “brimonidine or pharmaceutically acceptable salts thereof as a sole pharmaceutically active agent.” When read in light of the specification, the scope of “sole pharmaceutically active agent” is ambiguous. The specification teaches that beta blockers such as timolol are typically added to brimonidine therapy (page 2, para. 6) and that “these two active ingredients decrease elevated IOP by complementary mechanism of action and the combined effect results in additional IOP reduction compared to either compound administered alone” (page 3, para. 1). Accordingly, it is unclear whether claim 1 excludes timolol or encompasses compositions that include timolol as an additional pharmaceutically active agent. Because a person of ordinary skill would not be able to determine the metes and bounds of claim 1 with reasonable certainty, claim 1 is indefinite under 35 U.S.C. § 112(b). For purposes of examination, the phrase “as a sole pharmaceutically active agent” is treated as non-limiting and is not given patentable weight.
Claim 5 recites “a viscosity agent, wherein viscosity agent….” This phrasing is indefinite because it is unclear whether the “viscosity agent” in claim 5 is the same as, or different from, the “viscosity agent” in claim 1 (poly(vinyl alcohol)). Additionally, within the “wherein” clause of claim 5, it is unclear whether “viscosity agent” refers back to the viscosity agent introduced in claim 5 or to the viscosity agent of claim 1. For purposes of examination, “a viscosity agent, wherein viscosity agent…” in claim 5 is interpreted as referring to the poly(vinyl alcohol) recited in claim 1.
Claim 6, which depends from claim 5, presents a similar issue by reciting “the viscosity agent” without proper antecedent basis. It is unclear whether “the viscosity agent” refers to the same viscosity agent as in claim 5, or to the viscosity agent of claim 1.
Claims 7 and 8 are included in this rejection because they depend from the rejected claims 5 and 6, respectively.
Claims 2-10 are included in this rejection because they depend from the rejected claim 1.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ionna Rassia (EP 2886130; in IDS dated: 02/02/2013, hereinafter “Rassia”).
Rassia (para. [0006] – para. [0009]; para. [0035]; para. [0037] – para. [0040]; example 6; claims) discloses ophthalmic compositions comprising e.g. brimonidine without the use of any antimicrobial preservative compound. In example 6 such a composition is disclosed comprising 0.2 % w/v %brimonidine tartrate, 4.30 % w/v PVA, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, NaOH or HCI, and water, pH 6.2. The composition is filled in preservative-free multi-dose containers.
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Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mallard et al. (WO2020065085 A1-machine translation), published 04/02/2020.
Mallard discloses a topical pharmaceutical composition comprising brimonidine, its salts or derivatives (i.e., brimonidine tartrate), in between 0.01% and 1%, preferably between 0.05%-0.5% W/W, in oil-in-water (O/W) emulsion, wherein an aqueous phase comprising at least 0.01%by weight of the total weight of the composition (w/w) of water-soluble polyvinyl alcohol (PVA), (see claims 1-3).
Regarding “preservative free”, even though the prior art does not specifically identify said composition as “preservative free”, the composition prepared according to the Mallard may not include a preservative, thus the Mallard clearly anticipates the claim 1.
Regarding “ophthalmic” pharmaceutical composition, it is noted that statements in the preamble reciting the purpose or intended of the claimed invention is not automatically limiting or entitled to patentable weight: during examination, such statements must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference. In the instant application, when reading the preamble in the context of the entire claim, the recitation of "ophthalmic" is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention's limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. V. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein. See also MPEP § 2112 - MPEP § 2112.02. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dorr, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation".
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 5 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Likitler-Suang et al. (WO2012016000A2, hereinafter “Likitler-Suang”) in view of Jiao et al. (WO 2016149498 A1, hereinafter “Jiao”) and Olejnik et al. (WO 2002/05822 A2, hereinafter “Olejnik”).
The amended claim 1 recites “a preservative-free ophthalmic pharmaceutical composition comprising brimonidine or pharmaceutically acceptable salts thereof as a sole pharmaceutically active agent or in combination with timolol or pharmaceutically acceptable salts thereof, and poly(vinly alcohol) as a viscosity agent.
Likitler-Suang teaches or suggests a preservative free brimonidine and timolol composition(Page 1, lines 14 and 15), for lowering intraocular pressure, i.e., a preservative free ophthalmic composition (Claim 1), wherein the brimonidine in the preservative-free ophthalmic composition that is in the form of brimonidine tartrate in a weight percentage of 0.2% w/v (Claim 1 and claim 3 and Table 1); and the preservative-free ophthalmic composition also include timolol in the form of timolol maleate in a quantity of 0.68% (Table 1).
Likitler-Suang teaches or suggests that the composition contains “tonicity and buffer agents, and purified water…such as sodium phosphate dibasic heptahydrate and citric acid monohydrate and suitable tonicity agents such as sodium chloride” (page 2, lines 12-16; Table 1). As the specific embodiments of the invention, Table 1 discloses a composition comprising brimonidine tartrate, timolol maleate, sodium hydroxide, hydrochloric acid, sodium phosphate monobasic dihydrate, and purified water/water for injections in the preservative-free brimonidine and timolol composition.
Likitler-Suang teaches or suggests that the pH of the preservative free brimonidine and timolol composition is within the range of about 6.5 to about 7.3, which reads on about 6.4 or about 6.9 (page 2, lines 16-18); the composition is contained in a unit dose kit form (page 3, lines 1-2; claim 6); and the preservative-free brimonidine and timolol solutions that are tolerable, safe, provides the same or better drug bioavailability of similar compositions with preservatives, and that is safe for patients wearing contacts (page 2, lines 6-10).
Jiao that discloses an ophthalmic composition comprising brimonidine tartrate and timolol maleate (abstract; para. [0002]); the reference discloses a composition comprising 0.1% or 0.2% w/v of brimonidine tartrate and 0.68% w/v or 0.5% w/v of timolol maleate, sodium chloride, sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate and water (para. [0003], [0005]-[0008]) wherein the composition has a pH of about 7 or a pH of 7.0 and further comprises one or both sodium hydroxide and hydrochloric acid (para. [0004]). The reference also teaches or suggests that the composition can be prepared with or without preservative (para. [0009]; the formulation can be prepared with one or more viscosity enhancing agents, e.g., polyvinyl alcohol, that prolongs the residence time of brimonidine and timolol on corneal surface of the eye, thereby providing better ocular absorption (para. [0028]); the composition can be prepared in a unit dose or multidose package, free of preservatives (para. [0032]).
Olejnik is cited to demonstrate that polyvinyl alcohol and sodium citrate dihydrate are well-known excipients routinely used in ophthalmic compositions. Olejnik discloses an ophthalmic solution comprising 0.5% w/v brimonidine tartrate that contains 1.4% w/v polyvinyl alcohol and includes sodium citrate dihydrate (see, e.g., Abstract; Example, Table I).
Primarily, Likitler‑Suang does not disclose (i) the use of poly(vinyl alcohol) as a viscosity‑enhancing agent as recited in claim 1, and (ii) the limitation in claim 5 that the viscosity agent is present at a maximum of 1.4% w/v. In addition, Likitler‑Suang is silent as to preparing the composition in a multi‑dose preservative‑free container.
However, it would have been prima facie obvious to a person of ordinary skill in the art to add a viscosity‑enhancing agent, such as poly(vinyl alcohol) (PVA), at 1.4% w/v to the Likitler‑Suang composition as required by the instant claims. A skilled artisan would have been motivated to do so because increasing viscosity with PVA is known to prolong the residence time of brimonidine and timolol on the corneal surface, thereby improving ocular absorption, as taught by Jiao. The artisan would also have had a reasonable expectation of success because PVA is a well‑known viscosity‑enhancing agent, and the 1.4% w/v amount is taught by Jiao and/or Olejnik. Furthermore, Jiao teaches that preparing the preservative‑free formulation for packaging in a unit‑dose preservative‑free container or a multi‑dose container is within the purview of ordinary skill in the art.
Regarding “0.683% 2/v of timolol maleate” in claim 3, the instant specification discloses that timolol maleate in a concentration of 0.683% w/v is equivalent to 0.500% w/v timolol (Table 23). Likitler-Suang discloses 0.5% w/v timolol (claim 1), i.e., 0.500% w/v timolol, which suggests the 0.68% of timolol maleate disclosed by Likitler-Suang and the 0.683% timolol maleate of the instant claims are equivalent.
Even if assuming arguendo that the prior art concentration 0.68% w/v of timolol maleate is not equivalent to the instantly claimed concentration 0.683% w/v of timolol maleate, it would be prima facie obvious to one of ordinary skill in the art that 0.683% w/v timolol maleate, as required by the instant claims, and 0.68% timolol maleate, as disclosed by Likitler-Suang, that are sufficiently close such as to make the difference between the two a matter of routine optimization. As indicated in MPEP §2144.05(I): “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).”
Claims 1 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Likitler-Suang et al. (WO2012016000A2) in view of Jiao et al. (WO 2016149498 A1, hereinafter “Jiao”), Olejnik et al. (WO 2002/05822 A2), and further in view of JP 2020-33290 (machine translation, hereinafter “JP’290)).
The modified teaching of Likitler-Suang has been discussed above.
The modified teaching of Likitler-Suang differs from the claimed invention in adding “sodium phosphate monobasic dihydrate” to said composition in claim 9.
JP’290 is being supplied as a reference to demonstrate that sodium phosphate monobasic dihydrate or sodium phosphate monobasic monohydrate are well known additives that are utilized in a composition containing brimonidine or salt thereof (page 3).
The modified teaching of Likitler-Suang differs from the claimed invention in adding sodium phosphate monobasic dihydrate to said composition. However, it would be prima facie obvious to one of ordinary skill in the art to replace sodium phosphate monobasic monohydrate with sodium phosphate monobasic dihydrate as taught by JP’290. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention because both sodium phosphate monobasic dihydrate and sodium phosphate monobasic monohydrate are well known additives in brimonidine solution, and its prima facie obvious to substitute one art recognized equivalent for another.
Regarding the pH value of “about 6.9” in claim 10, the cited reference(s) disclose(s) ophthalmic formulations with pH ranges that encompass or overlap pH 6.4 (e.g., approximately 6.0–7.0). Where a claimed range overlaps or lies within a range disclosed by the prior art, a prima facie case of obviousness is established. See MPEP §2144.05(I); In re Peterson, 315 F.3d 1325, 1330–31 (Fed. Cir. 2003); Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Absent a showing of criticality for pH 6.4 or unexpected results, selection of a value within a known range constitutes routine optimization of a result-effective variable. See MPEP §2144.05(II); In re Aller, 220 F.2d 454, 456 (CCPA 1955). Accordingly, the recitation “about 6.4” does not patentably distinguish the claimed composition over the prior art.
Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Likitler-Suang et al. (WO2012016000A2) in view of Jiao et al. (WO 2016149498 A1), Olejnik et al. (WO 2002/05822 A2) as applied to claims 1-3 and 5 above, and further in view of Birk et al. (WO2018108764A1, hereinafter “Birk”).
The modified teaching of Likitler-Suang has been discussed above.
Primarily, the modified teaching of Likitler-Suang differs from the claimed invention in the selection of PVA grade 40-88 among polyvinyl alcohol in claim 6 and further inclusion of “citric acid monohydrate, sodium, citrate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide and water of injection” in claim 7, and the resultant composition of claim 7 having pH of “about 6.4”.
Birk et al. disclose that PVA grade 40-88 is high-viscosity and pharmacopoeia-compliant (Section 0006).
One having ordinary skill in the art would have been motivated to do so because grade40-88 PVA has a high viscosity and is pharmacopeia-compliant as taught by Birk. The skilled artisan would have a reasonable expectation of success because the modification would simply entail using PVA of a specific grade that is drug-compatible.
With respect to the further inclusion of citric acid monohydrate, sodium citrate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection, the cited reference(s) alone or in combination teach(es) that these are conventional components routinely used in ophthalmic solutions containing brimonidine and/or timolol. A person of ordinary skill in the art would have been motivated to incorporate these ingredients for their well‑established functions—namely, a citrate buffer system (citric acid monohydrate/sodium citrate dihydrate) to maintain the target pH, sodium chloride to adjust tonicity, hydrochloric acid and sodium hydroxide to fine‑tune pH, and water for injection as the vehicle—with a reasonable expectation of success and predictable results. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) (combining familiar elements according to known methods to yield predictable results); MPEP §§ 2143, 2144, and 2144.07. The proposed combination reflects the predictable use of prior‑art elements according to their established functions in brimonidine/timolol ophthalmic formulations and does not require more than routine optimization.
Regarding the pH value of “about 6.4” in claim 8, the cited reference(s) disclose(s) ophthalmic formulations with pH ranges that encompass or overlap pH 6.4 (e.g., approximately 6.0–7.0). Where a claimed range overlaps or lies within a range disclosed by the prior art, a prima facie case of obviousness is established. See MPEP §2144.05(I); In re Peterson, 315 F.3d 1325, 1330–31 (Fed. Cir. 2003); Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Absent a showing of criticality for pH 6.4 or unexpected results, selection of a value within a known range constitutes routine optimization of a result-effective variable. See MPEP §2144.05(II); In re Aller, 220 F.2d 454, 456 (CCPA 1955). Accordingly, the recitation “about 6.4” does not patentably distinguish the claimed composition over the prior art.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Likitler-Suang et al. (WO2012016000A2) in view of Jiao et al. (WO 2016149498 A1), Olejnik et al. (WO 2002/05822 A2and further in view of Ionna Rassia (EP 2886130 ) and Ranna et al. (US2018235873A1).
As discussed above, the modified teachings of Likitler-Suang disclose ophthalmic brimonidine formulations in combination with routine excipients. While Likitler-Suang does not expressly recite the specific physical parameter ranges of claim 4—namely, “a) viscosity of less than 10 cP at 25 °C …” and “b) surface tension of less than 70 mN/m …”—it would have been obvious to a person of ordinary skill in the art to arrive at those ranges for at least the following reasons:
The modified teaching of Likitler-Suang is silent as to the pharmaceutical composition having the specific parameters recited in claim 4, namely “a) viscosity of less than 10cP at 25 celcius…” and “b) surface tension of less than 70 mN/m …”.
Rassia (para.[0006]–[0009]; para.[0035]; para.[0037]–[0040], [0066]-[0072]; Example 6; Table 3a; claims) discloses ophthalmic compositions that include brimonidine and explicitly omit any antimicrobial preservative. Example 6 discloses a composition comprising 0.2 % w/v brimonidine tartrate, 4.30 % w/v PVA, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, NaOH or HCl, and water (pH 6.2) wherein the viscosity of the composition is 3.41 cP, and states that the composition is filled into preservative‑free multi‑dose containers. Rassia further teaches or suggests that optimization of drop size, pH, osmolality and viscosity—and avoidance of antimicrobial preservatives—to improve stability and permeability of ophthalmic formulations containing timolol and brimonidine is within the skill of the ordinary artisan (see para.[0033], [00423] and claims); and that “The surface tension is another parameter that needs to be considered…Reduction of the surface tension in an ophthalmic solution causes an increase of the surface area wetted by the solution during ophthalmic use, thereby ensuring better contact of the solution with the tear fluid on the eye surface and thus increase the absorption…The surface tension of the solution is adjusted by adding to the formulation of a suitable surfactant such as surfactants and wetting agents….(para. [0026]).
Rana et al. disclose that the surface tension of tear fluid has been found to be between 44 mN/m to 50 mN/m, that ophthalmic solutions should have a surface tension equal to the surface tension of tear fluid, and that the surface tension of an ophthalmic composition is a major determination of size of drop (Paragraph 0124).
Claim 4 does not identify specific excipients; it recites only that the composition of claim 1 “further comprising adequate quantity of pharmaceutically acceptable excipients selected so as to provide the following physical parameters to the solution…”. The specification itself discloses the same or similar excipients (e.g., citric acid monohydrate, sodium citrate dihydrate, sodium chloride, sodium hydroxide, hydrochloric acid, water for injection; Tables 2, 4, and 6), which are well known in the art as taught by Rassia (Table 3), Likitler‑Suang (page 2, lines 12–16; Table 1), Jiao (Table I) and Olejnik (Table 1).
Although the cited prior art does not expressly disclose the specific viscosity range measured by the European Pharmacopoeia or the particular surface‑tension range recited in claim 4, the prior art compositions contain the same ingredients, and the applicant’s own disclosure supports that those prior compositions can yield the claimed physical characteristics. Under these circumstances, the burden properly shifts to the applicant to demonstrate otherwise. As noted in MPEP §2113.III: “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” See also In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
To the extent claim 4 specifies viscosity “measured by” a particular standard (e.g., a European Pharmacopoeia method), selecting a conventional test protocol to characterize an inherent property does not patentably distinguish over the prior art where the same compositions would meet the recited range when measured by that standard. See MPEP § 2112.
Alternatively, even assuming arguendo that the exact parameter ranges are not inherently disclosed in the prior art, a person of ordinary skill would have been motivated to adjust viscosity and surface tension—together with pH, osmolality, specific gravity, and drop size—to improve stability, ocular retention, comfort, and permeability of preservative‑free brimonidine solutions. A skilled artisan would have had a reasonable expectation of success in doing so using routine excipient adjustments taught by Likitler-Suang, Jiao, Olejnik, and Rassia. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) (combination of familiar elements according to known methods to yield predictable results); MPEP § 2144.05 (optimization of result‑effective variables); In re Aller, 220 F.2d 454 (CCPA 1955). It would have been routine to vary the amounts of known excipients to arrive at the claimed composition, which reasonably includes viscosity < 10 cP at 25 °C and surface tension < 70 mN/m and < 50 mN/m at 25 °C.
Surface tension is a classic result‑effective parameter that a person of ordinary skill would routinely optimize. Optimization of such parameters is standard practice and would have been obvious to attempt with a reasonable expectation of success. Determining the optimal surface tension would have been customary to obtain advantageous drop size and to approximate tear fluid properties. Where the general conditions of a claim are disclosed in the prior art, discovering optimum or workable ranges by routine experimentation is not inventive. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955). Rana et al. disclose that tear fluid surface tension falls between 44 and 50 mN/m, state that ophthalmic solutions should match tear fluid surface tension, and identify surface tension as a major determinant of drop size. Given these teachings, the Examiner correctly views optimization of surface tension to achieve a known effect as prima facie obvious, absent evidence of unexpected superior properties.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application,
or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-8 and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11229596 in view of Ionna Rassia (EP 288613) and Olejnik et al. (WO 2002/05822 A2), and further in view of Birk et al. (WO2018108764A1) or Ranna et al. (US2018235873A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to essentially the similar or same ophthalmic composition comprising brimonidine or pharmaceutically acceptable salts thereof and a viscosity agent.
Patented claim:
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Since the transitional phrase “comprising” is an open-ended (inclusive) term. It generally permits additional ingredients to be present in the claimed composition. Thus, the examiner determines that the scope of the patented claim 1 falls within the scope of the instant claim 1.
It is noted that a phrase like “sole active ingredient”
With respect to claims 1, 2 and 11,
Regarding the instantly claimed “a preservative free” and inclusion of poly(vinyl alcohol) as the specific viscosity agent recited in claim 1 and 0.2% w/v of brimonidine tartrate, Rassia teaches an ophthalmic compositions comprising e.g. brimonidine without the use of any antimicrobial preservative compound, specifically Example 6 such discloses a composition comprising 0.2 wt% brimonidine tartrate, 4.30 wt% PVA, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, NaOH or HCI, and water, pH 6.2, wherein the viscosity of the composition is 3.41 cP and the composition is filled in preservative-free multi-dose containers (para. [0006] – para. [0009]; para. [0025], [0035]; para. [0037] – para. [0040]; example 6; claims). Rassia also teaches that “the high incidence of local side effects attributed to preservative…preservative can cause serious inflammatory effects such as chemical irritation, hyper-reactivity and true allergies…” (para. [0036]; and that by addition to the formulation of suitable viscosity enhancing agents, cause a reduced flow of liquid in the application to the eye, prolongation of the contact time with cornea tissue and eventually increase the adsorption of the active substance (para. [0024]).
One having ordinary skill in the art would have been motivated to modify the patented claim 1 of US’596 with reasonable expectation of success to arrive at the instant claimed invention. It would have been primary facies obvious to one of the ordinary skill in the art to select polyvinyl alcohol which is one of most commonly used viscosity-increasing agent and furthermore motivated to formulate the ophthalmic composition without a preservative to prevent adverse effects associated with the preservative.
With respect to the claim 4,
Rana et al. disclose that the surface tension of tear fluid has been found to be between 44 mN/m to 50 mN/m, that ophthalmic solutions should have a surface tension equal to the surface tension of tear fluid, and that the surface tension of an ophthalmic composition is a major determination of size of drop (Paragraph 0124).
Claim 4 does not identify specific excipients; it recites only that the composition of claim 1 “further comprising adequate quantity of pharmaceutically acceptable excipients selected so as to provide the following physical parameters to the solution…”. The specification itself discloses the same or similar excipients (e.g., citric acid monohydrate, sodium citrate dihydrate, sodium chloride, sodium hydroxide, hydrochloric acid, water for injection; Tables 2, 4, and 6), which are well known in the art as taught by Rassia (Table 3), Likitler‑Suang (page 2, lines 12–16; Table 1), Jiao (Table I) and Olejnik (Table 1).
Although the cited prior art does not expressly disclose the specific viscosity range measured by the European Pharmacopoeia or the particular surface‑tension range recited in claim 4, the prior art compositions contain the same ingredients, and the applicant’s own disclosure supports that those prior compositions can yield the claimed physical characteristics. Under these circumstances, the burden properly shifts to the applicant to demonstrate otherwise. As noted in MPEP §2113.III: “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” See also In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
To the extent claim 4 specifies viscosity “measured by” a particular standard (e.g., a European Pharmacopoeia method), selecting a conventional test protocol to characterize an inherent property does not patentably distinguish over the prior art where the same compositions would meet the recited range when measured by that standard. See MPEP § 2112.
Alternatively, even assuming arguendo that the exact parameter ranges are not inherently disclosed in the prior art, a person of ordinary skill would have been motivated to adjust viscosity and surface tension—together with pH, osmolality, specific gravity, and drop size—to improve stability, ocular retention, comfort, and permeability of preservative‑free brimonidine solutions. A skilled artisan would have had a reasonable expectation of success in doing so using routine excipient adjustments taught by Likitler-Suang, Jiao, Olejnik, and Rassia. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) (combination of familiar elements according to known methods to yield predictable results); MPEP § 2144.05 (optimization of result‑effective variables); In re Aller, 220 F.2d 454 (CCPA 1955). It would have been routine to vary the amounts of known excipients to arrive at the claimed composition, which reasonably includes viscosity < 10 cP at 25 °C and surface tension < 70 mN/m and < 50 mN/m at 25 °C.
Surface tension is a classic result‑effective parameter that a person of ordinary skill would routinely optimize. Optimization of such parameters is standard practice and would have been obvious to attempt with a reasonable expectation of success. Determining the optimal surface tension would have been customary to obtain advantageous drop size and to approximate tear fluid properties. Where the general conditions of a claim are disclosed in the prior art, discovering optimum or workable ranges by routine experimentation is not inventive. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955). Rana et al. disclose that tear fluid surface tension falls between 44 and 50 mN/m, state that ophthalmic solutions should match tear fluid surface tension, and identify surface tension as a major determinant of drop size. Given these teachings, the Examiner correctly views optimization of surface tension to achieve a known effect as prima facie obvious, absent evidence of unexpected superior properties.
With respect to claims 5-6,
Olejnik is cited to demonstrate that polyvinyl alcohol and sodium citrate dihydrate are well-known excipients routinely used in ophthalmic compositions. Olejnik discloses an ophthalmic solution comprising 0.5% w/v brimonidine tartrate that contains 1.4% w/v polyvinyl alcohol and includes sodium citrate dihydrate (see, e.g., Abstract; Example, Table I).
Birk et al. disclose that PVA grade 40-88 is high-viscosity and pharmacopoeia-compliant (Section 0006).
It would have been prima facie obvious to a person of ordinary skill in the art to further modify the patented claim 1 of US’596 by adding 1.4% w/v of poly(vinyl alcohol) (PVA) as the viscosity enhancing agent to the composition modified by Rassia. Where a claimed range overlaps or lies within a range disclosed by the prior art, a prima facie case of obviousness is established. See MPEP §2144.05(I); In re Peterson, 315 F.3d 1325, 1330–31 (Fed. Cir. 2003); Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Absent a showing of criticality for pH 6.4 or unexpected results, selection of a value within a known range constitutes routine optimization of a result-effective variable. See MPEP §2144.05(II); In re Aller, 220 F.2d 454, 456 (CCPA 1955). Accordingly, the recitation “about 6.4” does not patentably distinguish the claimed composition over the prior art.
Furthermore, one having ordinary skill in the art would have been motivated to do so because grade40-88 PVA has a high viscosity and is pharmacopeia-compliant as taught by Birk. The skilled artisan would have a reasonable expectation of success because the modification would simply entail using PVA of a specific grade that is drug-compatible.
With respect to claims 7-8,
The cited references alone or in combination makes clear that i) citric acid monohydrate, sodium citrate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection are conventional components routinely used in ophthalmic solutions containing brimonidine. A person of ordinary skill in the art would have been motivated to incorporate these ingredients for their well‑established functions—namely, a citrate buffer system (citric acid monohydrate/sodium citrate dihydrate) to maintain the target pH, sodium chloride to adjust tonicity, hydrochloric acid and sodium hydroxide to fine‑tune pH, and water for injection as the vehicle—with a reasonable expectation of success and predictable results. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) (combining familiar elements according to known methods to yield predictable results); MPEP §§ 2143, 2144, and 2144.07. The proposed combination reflects the predictable use of prior‑art elements according to their established functions in brimonidine/timolol ophthalmic formulations and does not require more than routine optimization.
Regarding the pH value of “about 6.4” in claim 8, the cited reference(s) disclose(s) ophthalmic formulations with pH ranges that encompass or overlap pH 6.4 (e.g., approximately 6.0–7.0). Where a claimed range overlaps or lies within a range disclosed by the prior art, a prima facie case of obviousness is established. See MPEP §2144.05(I); In re Peterson, 315 F.3d 1325, 1330–31 (Fed. Cir. 2003); Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Absent a showing of criticality for pH 6.4 or unexpected results, selection of a value within a known range constitutes routine optimization of a result-effective variable. See MPEP §2144.05(II); In re Aller, 220 F.2d 454, 456 (CCPA 1955). Accordingly, the recitation “about 6.4” does not patentably distinguish the claimed composition over the prior art.
Response to Arguments
Applicant's arguments filed 09/11/2025 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
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/BRIAN-YONG S KWON/ Supervisory Patent Examiner, Art Unit 1613