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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 06/22/2026 is acknowledged. Claims 17-33 read on the elected invention. Accordingly, claims 34-36 are withdrawn further consideration pursuant to 37 CFR 1.142(b).
Claim Rejections - 35 USC § 112(b)
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.
Claim 26 is 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 26 recites the limitation "the pH drift of the composition" in dependence to claim 25 (ultimately independent claim 17). There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 17-20, 22-25 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Koneru et al. (US 10028921 B1, hereinafter “Koneru”) and/or, if necessary, further in view of Flink et al. (WO 99/37329 A1, hereinafter “Flink”).
Independent claim 17 is drawn to an aqueous composition for parenteral administration comprising a pharmaceutically effective amount of vitamin K, a polyethoxylated castor oil, and a citrate buffer in a concentration of 1 to 40 mmol/L, wherein the pH of the composition is between 3.5 and 7.0.
The instant specification identifies “Kolliphor EL” as the polyethoxylated castor oil, which is also known as Cremophor EL, and states that it is prepared by reacting castor oil with ethylene oxide in a molar ratio of 1:35 and that Kolliphor EL is also known under the generic names macrogolglycerol ricinoleate polyoxyl-35-castor oil or PEG-35 castor oil respectively (para. [0012]). The specification also identifies “citrate” as citric acid and its mono-, di-, and tri-deprotonated anions, as well as pharmaceutically acceptable salts and hydrates thereof (para. [0014]).
Regarding claims 17-25,
Koneru teaches or suggests a composition comprising vitamin K, specifically phytonadione, in a concentration range from 100 µg/mL to about 20 mg/mL, a polyethoxylated fatty acid derivative such as Cremophor EL, which reads on the instant “polyethoxylated castor oil” or “macrogolglycerol ricinoleate polyoxyl-35-castor oil”, a buffer such as citrate/citric acid, hydrochloric acid, acetic acid, and other additives such as benzyl alcohol and dextrose such as dextrose monohydrate, for parenteral administration or injection, wherein the composition has a pH of from about 3.5 to about 8 (entire document; abstract; col. 5, lines 4-11; col. 6, lines 24-40; col. 7, lines 24-31 and 45-52). Even though Koneru does not expressly disclose the concentration range of Cremophor EL in the disclosed composition, Table 1 shows various amounts from 14mg to 60mg. Koneru further teaches that benzyl alcohol may be included as an optional ingredient, and that removal of benzyl alcohol is recommended when the formulation is used in pediatric populations (col. 5, lines 30-32; Examples; col. 8, lines 30-59).
Even though Koneru does not expressly disclose the specific amount or concentration range of citrate/citric acid buffer recited in the claims, Koneru teaches or suggests the use of citrate/citric acid as a buffering agent for adjusting the pH of the composition within the overlapping range of about 3.5 to about 8, and more preferably pH 5-7, pH 4-6, or pH 3.5-7 (see Tables 1-2). Accordingly, selecting any particular concentration or amount of citrate/citric acid buffer would have been no more than a matter of routine optimization of a result-effective variable, and thus would have been obvious. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Alternatively, Flink is cited as supplemental evidence that citrate buffer concentrations within the range of “1 to 40 mmol/L” or “1 to 20 mmol/L” were well within the level of ordinary skill in the art. In particular, Flink teaches the use of citrate buffer in the range of 5 mmol/L to 20 mmol/L to adjust the pH of a formulation to about 5.3 to about 7.2 (page 2, lines 17-23; page 3, lines 4-11). Therefore, the claimed citrate buffer concentration range would have been obvious over Koneru further in view of Flink.
Further, where claimed ranges overlap or lie within ranges disclosed by the prior art, a prima facie case of obviousness exists. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). Koneru discloses a pH range of about 3.5 to about 8, which overlaps the pH recited in claim 17 and encompasses the ranges recited in claims 19 and 25. Koneru also discloses phytonadione concentrations from 100 µg/mL to about 20 mg/mL, which overlap the ranges recited in claims 23 and 24, including 0.1 to 50 mg phytonadione per mL, 2 mg phytonadione per mL, and 10 mg phytonadione per mL, whereas the reference discloses 60mg of Cremophor EL in Formula 3, which overlaps the concentration range of 30 to 150mg recited in claim 21. Accordingly, the claimed ranges would have been prima facie obvious.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the claimed combination of known components from Koneru because the claimed invention amounts to no more than the predictable use of prior art elements according to their established functions. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-21 (2007). The cited reference provides a reason to combine vitamin K, Cremophor EL, and citrate/citric acid buffer in a parenteral formulation having the claimed pH range, and no evidence of criticality or unexpected results has been presented for the particular amounts or ranges recited. Accordingly, claims 17-20, 22-25 and 28 are unpatentable over Koneru and/or, if necessary, further in view of Flink.
Regarding claim 28,
Koneru’s composition does not teach or suggest the presence of butylated hydroxyanisole or butylated hydroxytolune in the disclosed composition. Because the reference is silent as to these ingredients, Koneru reasonably suggests a composition that excludes butylated hydroxyanisole or butylated hydroxytoluene, as required by the instant claim. The absence of these components does not patentably distinguish the claimed composition from Koneru, particularly where no criticality or unexpected has been shown for their exclusion. See, e.g., MPEP § 2144.05 and In re Aller, 220 F.2d 454, 456 (CCPA 1955). Accordingly, claim 28 would have been obvious over Koneru.
Claim(s) 29-30 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Koneru et al. (US 10028921 B1, hereinafter “Koneru”) as applied to claims 17-20, 22-25 and 28 above in view of Product Information Sheet (“Phytonadione Phytonadione-phytonadione injection, emulsion”, Dr. Reddy’s Laboratories Inc, 1 May 2019, cited in PTO-1449, hereinafter “Dr. Redddy’s Phytonadione”) and Product Information Sheet (“Phytonadione=phytonadione injection, emulsion”, International medication Systems, Limited, cited in PTO-1449, hereinafter “International Medication Systems”) and/or if necessary, further in view of Flink et al. (WO 99/37329 A1, hereinafter “Flink”).
The modified teaching of Koneru is silent as to i) the presence of glacial acetic in said composition and ii) the specific amounts of each components in the disclosed composition, particularly “2mg phytonadione per mL…5 mmol citrate buffer per liter…37.5mg dextrose monohydrate per mL…9mg benzyl alcohol per mL..70mg macrogolglycerol ricinoleate poly-35-castor oil per mL” or “10mg phytonadione per mL…5 mmol citrate buffer per liter…37.5mg dextrose monohydrate per ml…9mg benzyl alcohol per mL..70 mg macrogolglycerol ricinoleate polyoxyl-35-castor oil per mL”.
Dr. Reddy’s Phytodione discloses a phytonadione injection emulsion comprising 10mg of phytonadione, polyoxyl 35 castor oil, dextrose monohydrate, water, benzyl alcohol and hydrochloric acid for pH adjustment, from pH of 5 to 7 (e.g., 6.3).
International Medical Systems discloses a phytonadione injection emulsion comprising 1mg (1mg/0.5 mL) of phytonadione, 10mg polysorbate, 10.4mg propylene glycol, 0.17mg sodium acetate anhydrous and 0.000002mL glacial acetic acid and water, wherein additional glacial acetic acid or sodium acetate anhydrous can be added to adjust the pH from pH of 3.5 to 7 (e.g., 6.3).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the claimed combination of known components because the claimed invention amounts to no more than the predictable use of prior art elements according to their established functions. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-21 (2007). Furthermore, selecting any particular concentration or amount of known components would have been no more than a matter of routine optimization of a result-effective variable, and thus would have been obvious. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The cited references provide a reason to combine vitamin K, Cremophor EL, citrate/citric acid buffer, dextrose monohydrate, benzyl alcohol and/or glacial acetic acid and water in a parenteral formulation having the claimed pH range, and no evidence of criticality or unexpected results has been presented for the particular amounts or ranges recited.
Claims 26-27, 31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Koneru et al. (U.S. Patent No. 10,028,921 B1, hereinafter “Koneru”), as applied to claims 17-20, 22-25, and 28 above, in view of Product Information Sheet (“Phytonadione Injection, Emulsion,” Dr. Reddy’s Laboratories Inc., May 1, 2019, cited in PTO-1449, hereinafter “Dr. Reddy’s Lab”) and Product Information Sheet (“Phytonadione Injection, Emulsion,” International Medication Systems, Limited, cited in PTO-1449, hereinafter “International Medication Systems”), and/or, if necessary, further in view of Flink et al. (WO 99/37329 A1, hereinafter “Flink”), and/or Wu et al. (WO 2021/190582 A1, English translation, hereinafter “Wu”).
The modified teaching of Koneru is silent as to the specific parameters recited in the claims, such as “pH is less than 0.2 pH units following storage for 3 months at 40 °C or for 12 months at 25 °C” and/or the theoretical amount of phytonadione in the composition in the range of “97% to 103%” following storage for 3 months at 40 °C or for 12 months at 25 °C. However, selecting an optimum pH to provide a more stable composition, i.e., to avoid pH drift during storage, would have amounted to no more than routine optimization of a result-effective variable.
Furthermore, the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise.
It is well settled 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, 456, 105 USPQ 233, 235 (CCPA 1955). Generally, differences in concentration, pH range, or temperature do not support patentability where the claimed subject matter is otherwise encompassed by the prior art, absent evidence that such ranges are critical.
Alternatively, Wu is relied upon as a supplemental reference to show that it was well known to those of ordinary skill in the art that, in preparing pharmaceutical formulations, pH drift may occur when the pH of the formulation differs from the pH of the buffer. Wu further teaches that it is desirable to maintain the pH of the pharmaceutical composition at or near the pH of the buffer, typically within ±0.3, preferably within ±0.2, and more preferably within ±0.1. See Wu, page 1, under “Description.” Thus, maintaining pH drift at less than 0.2 pH units, as well as achieving the claimed theoretical amount of phytonadione (by maintaining the pH drift of the composition less than 0.2pH units) to provide improved stability and drug availability, would have been obvious to one of ordinary skill in the art as a matter of routine optimization of a result-effective parameter.
Conclusion
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/BRIAN-YONG S KWON/ Supervisory Patent Examiner, Art Unit 1613
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