Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 1-10 are cancelled.
Claims 11-30 are pending.
Priority
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 11-30 are rejected under 35 U.S.C. 103(a) as being unpatentable over CN101766568A; (English translation provided) and Sugiyama et al. (US5651991) and Hosokawa et al. (CN1227490A; English translation provided).
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).
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical formulation and possess specialized knowledge in drug delivery, material science, and physical chemistry to convert active pharmaceutical ingredients (APIs) into stable, effective medicines. They understand how to select excipients (inactive ingredients), optimize stability, and ensure compliance with regulatory standards (FDA, GMP). Their expertise covers formulation development, dosage form design, and manufacturing processes.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 11-17 and 21-28, CN101766568 teaches in Example 1 [0017] a composition of:
An effective amount of clevidipine 1g (0.1%) (a);
A lipid soybean oil 200 g (20%) (c);
Emulsifier soy lecithin (which is soybean phospholipids) 20 g (2.0%) (d);
Tonicity agent/osmotic pressure adjusting agent glycerol 22 g (2.2%) (e);
Chelating antimicrobial agent EDTA calcium salt 0.1 g (0.01%) (b); and
Water (g) to 1000 ml.
See also claims 1-9. The same components implicitly make the composition of CN101766568 stable and resistant to microbial growth. CN101766568 teaches that the emulsion preparation is for quickly lowering the blood pressure and treatment of hypertension (page 2, Description; claim 9), thus reading on methods of administering the composition to a patient in need thereof for treating hypertension.
Further regarding claims 11 and 21, CN101766568 teaches that the emulsifiers include but are not limited to ionic surfactants such as cholic acid and deoxycholic acid, and may be one or several [0010]. Thus, when more than one emulsifier is present it indicates an emulsifier and co-emulsifier (f).
Further regarding claims 14 and 25, CN101766568 discloses that the oil phase includes, but are not limited to, soybean oil, castor oil, safflower oil, olive oil, cottonseed oil, sunflower oil, sesame oil, peanut oil, corn oil, medium chain triglycerides, glycerol triacetate, fatty acid monoglyceride or di-fatty acid glycerides and other pharmaceutically acceptable oils, may be a mixture of one or more of the above-described esters (claim 4).
Further regarding claims 16 and 27, CN101766568 discloses phospholipids including egg yolk phospholipids and soya phospholipids and their hydrogenated derivatives, phosphatidylcholine, synthetic phosphatidylcholine and hydrogenated derivatives thereof, poloxamers, cholic acid, deoxycholic acid, for example (claim 5).
Regarding claims 18 and 29, CN101766568 discloses that the pH is 6-8 [0019] which is overlaps the claimed range of about 6.0 to about 8.8.
Regarding claim 20, since CN101766568 discloses the same amount of antimicrobial chelating EDTA as claimed, then the composition inherently delays or retards microbial growth such that there is less than 10-fold (1 log) increase in viable microbial colonies over a 24-hour period. See MPEP 2112.01 II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).”
Regarding claims 11, 19 and 21, Sugiyama et al. teach fatty emulsion drug carrier compositions (Abstract) that has utility in administration of dihydropyridine calcium antagonists because they are sparingly soluble in water (Column 32, lines 5-13). Sugiyama et teach an emulsion comprising a calcium antagonist, a lipid such as soybean oil and a phospholipid (Claims 1 and 8). Sugiyama et al. teach oleic acid, stearic acid and palmitic acids as emulsification aids (Column 8, lines 18-22).
Regarding claims 11, 19 and 21, Hosokawa et al. teach fatty emulsion compositions (Title) where if necessary an emulsifying auxiliary agent can be added (Page 4, 4th paragraph) where emulsifying auxiliary agent is an adjuvant for emulsifying fat emulsions includes palmitic acid, stearic acid and preferably oleic acid in an amount of 3% (w/v) or less and preferably 1% (w/v) (Page 4, 5th paragraph) and teach an emulsion with soybean oil and oleic acid and phosphatidylcholine (Page 5, 4th paragraph).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and CN101766568 is that CN101766568 do not expressly teach adding about 0.01-2.0% w/v of oleic, stearic or palmitic acids or their pharmaceutically acceptable salts co-emulsifier to the composition for use in the method of treating acute hypertension. This deficiency in CN101766568 is cured by the teachings of Sugiyama et al. and Hosokawa et al. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the formulation of CN101766568 and add about 0.01-2.0% w/v of oleic or stearic or palmitic acids or their pharmaceutically acceptable salts co-emulsifier, as suggested by Sugiyama et al. and Hosokawa et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. Sugiyama et al. teach that dihydropyridine calcium antagonists are known to be only sparingly water soluble and to add oleic, stearic and palmitic acids as emulsification aids. It is known through Hosokawa et al. to add less than 3% and preferable 1% (w/v) of emulsifying adjuvants stearic and palmitic acids and preferably oleic acid. It is then obvious to employ less than 3% and preferable 1% (w/v) oleic, stearic and/or palmitic acids as suitable options for an emulsification aid for the sparingly soluble dihydropyridine calcium antagonist clevidipine emulsion of CN101766568 and use the composition to treat acute hypertension in a patient in need thereof with a reasonable expectation of success. It is within the skill of the ordinary artisan to ascertain whether the hypertension is acute or chronic and the pharmaceutical formulation is reasonable expected to treat any hypertension including acute hypertension.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the combined teachings of the references, 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 combined references, especially in the absence of evidence to the contrary.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 11-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11103490. Although the claims at issue are not identical, they are not patentably distinct from each other because anticipates the claimed subject matter by disclosing compositions comprising in claims 1:
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And in claim 6:
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The patent does not expressly teach the co-emulsifier is stearic acid (C18) or palmitic acid (C16). However, the scope for the co-emulsifier the specification defines a co-emulsifier as oleic acid, stearic acid and palmitic acid (column 6, lines 47-56). See MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.” While the patent does not claim methods of treating acute hypertension, clevidipine is approved for treatment of acute hypertension and the normal and usual operation of the composition is to treat acute hypertension. Consequently, administration to a patient in need thereof is obvious over disclosure of the formulation. Accordingly, the ordinary artisan would have recognized the obvious variation of the instant claimed subject matter over the patented subject matter.
Claims 11-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10010537. Although the claims at issue are not identical, they are not patentably distinct from each other because anticipates the claimed subject matter by disclosing compositions comprising, for example:
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The patent does not express teach wherein microbial growth is delayed or retarded such that there is less than 10-fold (1 log) increase in viable microbial colonies over a 24-hour period. However, the functional parameter is inherent in the composition because it comprises the same components. See MPEP 2112.01 II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).”
The patent does not expressly teach the co-emulsifier is stearic acid (C18) or palmitic acid (C16). However, the scope for the co-emulsifier the specification defines a co-emulsifier as oleic acid, stearic acid and palmitic acid (column 6, lines 43-54). See MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.”. Accordingly, the ordinary artisan would have recognized the obvious variation of the instant claimed subject matter over the patented subject matter.
While the patent does not claim methods of treating acute hypertension, clevidipine is approved for treatment of acute hypertension and the normal and usual operation of the composition is to treat acute hypertension. Consequently, administration to a patient in need thereof is obvious over disclosure of the formulation.
Accordingly, the ordinary artisan would have recognized the obvious variation of the instant claimed subject matter over the patented subject matter.
Claims 11-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 8658676. Although the claims at issue are not identical, they are not patentably distinct from each other because anticipates the claimed subject matter by disclosing compositions comprising, for example:
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The patent does not expressly teach the amount of oleic acid is about 0.01 to about 2.0% w/v. However, the patent does teach addition of oleic acid (claim 7) and it is merely routine optimization by the ordinary artisan to determine the optimal amount of oleic acid to add. See MPEP 2144.05 (II) (A): “[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)…see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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.").
The patent does not expressly teach the co-emulsifier is stearic acid (C18) or palmitic acid (C16). However, the scope for the co-emulsifier the specification defines a co-emulsifier as oleic acid, stearic acid and palmitic acid (column 6, lines 32-43). See MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.” Accordingly, the ordinary artisan would have recognized the obvious variation of the instant claimed subject matter over the patented subject matter.
While the patent does not claim methods of treating acute hypertension, clevidipine is approved for treatment of acute hypertension and the normal and usual operation of the composition is to treat acute hypertension. Consequently, administration to a patient in need thereof is obvious over disclosure of the formulation.
Accordingly, the ordinary artisan would have recognized the obvious variation of the instant claimed subject matter over the patented subject matter.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US5739152 teaches pharmaceutical emulsions for intravenous administration comprising a short acting dihydropyridine compound, a lipid phase, an emulsifier and water or a buffer (Abstract; claims 1-10).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613