DETAILED ACTION
Claims 1-20 are pending in the instant application.
2. Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. V. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966). These claims are withdrawn from consideration.
3. Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 1-20 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1-20 are rejected because the term “An injectable composition comprising temsirolimus for use in treating restenosis” is confusing. Are they claiming “composition” or “method for treating”? Correction is required.
Claims 2-5, 17-20 depend directly or indirectly from claim 1, which recites a composition of matter (injectable composition) comprising temsirolimus and a pharmaceutically acceptable excipient. Claims 2-5, 17-20 recite limitations pertaining to what the composition is claimed to be “suitable for” in claim 1 (claims 2-5) or tissue or vascular disease site intended to be treated with the composition (claims 17-20).
As the intended use of the claimed composition is not afforded patentable weight and claims 2-5 and 17-20 do not place any structural limitations on the claimed “injectable composition” of claim 1, they fail to further limit the injectable composition.
Applicants may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claims 1-20 are rejected because the term “suitable for” is confusing.
A claim term is functional when it recites a feature “by what it does rather than by what it is “(e.g., as evidenced by its specific structure or specific ingredients). In re Swinehart, 439 F.2d 210, 212, 169 USPQ 226, 229 (CCPA 1971). A functional limitation must be evaluated and considered, just like any other limitation of the claim, for what it fairly conveys to a person of ordinary skill in the pertinent art in the context in which it is used. A functional limitation is often used in association with an element, ingredient, or step of a process to define a particular capability or purpose that is served by the recited element, ingredient or step. See MPEP 2173.05(g).
Here, “suitable for” is a functional language, reciting features of the claimed injectable composition not by what it is but by what it does. The Examiner has fully and carefully considered this functional language and had determined that it does not place any patentable limitations on the claims because any “injectable composition” comprising temsirolimus and a pharmaceutically acceptable excipient would reasonably be “suitable for” adventitial delivery to the peripheral artery or direct injection to a vascular disease site. For example, dependent claims broadly recite therapeutically amount from about 1 mg to 50 mg (Claim 6), injection volumes from about 0.01 ml to about 50 ml (Claim 9), and concentrations of from about 0.01 mg/ml to about 2.0 mg/ml (Claim 13). Correction is required.
4. Claim Rejections - 35 USC § 102
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 1-13, 16-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rubino et al., US 2004/0167152. Rubino et al. teach parenteral formulations of CCI-779. (see abstract). As per claims 1-6, 9-12, 16-20, Rubino et al. teach an injectable composition compriing 25 mg/ml temsirolimus (CCI0779), dehydrated ethanol, citric acid, d,I-α-tocopherol, and propylene glycol. See rxamle 2; claims.
Also, as per claims 1-13, 16-20, Rubino et la. Teach a diluent comprising 5% w/v polysorbate 80, 5% w/v polyethylene glycol 400, and water for injection. Rubino et al. teach this diluent can be preferably combined in a ratio of 9:1 v/v with the cosolvent concentrate of Example 1 or 2 to produce a solution of CCI-779 at a concentration of 2.5 mg/ml, which resulting mixture can be injected directly or further diluted with 0.9% Sodium Chloride Injection to provide a solution for intravenous injection. This diluent, when combined with the CCI-779 formulations in Examples 1 and 2, has been used to deliver doses of 0.5 to 500 mg CCi-779 via direct intravenous injection or intravenous infusion. See example 4, Claims. Therefore, the instant claims are anticipated by Rubino et al.
Claims 1-20 are rejection under 35 U.S.C. 102(a)(1) as being anticipated by TORISEL PRODUCT LABLE (Wyeth Pharmaceuticals, Inc., 2007, 21 pages).
Torisel Product Label teaches Torisel (temsirolimus) injection, for intravenous infusion. See page 1.
Torisel injection, 25 mg/ml is supplied with diluent for Torisel. Torisel (temsirolimus) injection vial contents are first diluted with the enclosed diluent before diluting the resulting solution with 250 ml of 0.9% sodium chloride injection. See page 1, “Dosage and Administration”; page 1, “Dosage Forms and Strengths”.
As per claims 1-12, 17-20 in preparing the Torisel administration solution, Step 1 comprises injection 1.8 mL of DILUENT for TORISEL into the vial of TORISEL (temsirolimus) injection (25 mg/ml). the TORISEL (temsirolimus) vial contains an overfill of 0.2 ml (30 mg/1.2 ml). due to the intentional overfill in the TORISEL injection vial, the drug concentration of the resulting solution will be 10 mg/ml. a total volume of 3 ml will be obtained including the overfill. See page 3, 2.5 instructions for preparation and Administration.
As per claims 13-16, the required amount of temsirolimus from the 10 mg/ml drug solution/diluent mixture prepared in Step 1 is withdrawn and injected rapidly into a 250 mL container (glass, polyolefin, or polyethylene) of 0.9% sodium chloride injection. As the 10 mg/mL drug solution/diluent mixture has a volume of 3 mL, the maximum concentration of the resulting injectable composition is 0.12 mg/mL [30 mg in 250 mL 0.9% sodium chloride]. See page 3, 2.5 Instructions for Preparation and Administration.
As per claim 16, TORISEL (temsirolimus) injection comprises 25 mg/mL temsirolimus active ingredient and the inactive ingredients dehydrated alcohol (39.5% w/v), dI-alpha-tocopherol (0.075% w/v), propylene glycol (50.3% w/v), and anhydrous citric acid (0.0025% w/v). The DILUENT for TORISEL comprises the inactive ingredients polysorbate 80 (40.0% w/v), polyethylene glycol 400 (42.8% w/v), and dehydrated alcohol (19.9% w/v0. See pages 12-13.
5. Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S.
1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-20 are rejected under 103(a) as being unpatentable over Rubino et al., (US 2004/0167152) and TORISEL PRODUCT LABEL (Wyeth Pharmaceuticals, Inc., 2007).
Claimed Invention
The claims recite injectable compositions comprising temsirolimus or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. See claim 1.
As discussed supra, the intended use of the claimed injectable compositions, i.e., for treating restenosis, has no patentable weight. Additionally, limitations pertaining to what the composition is “suitable for” are likewise afforded no patentable weight as they do not place any physical or structural limitations on the claimed injectable composition. Put differently, any composition comprising a therapeutically effective amount of temsirolimus and a pharmaceutically acceptable excipient that is “injectable” is construed to be “suitable for” adventitial delivery to a peripheral artery or direct injection to a vascular disease site.
Teachings of RUBINO ET AL.
Rubinino et al. teach parenteral formulations of CCI-779. (see abstract).
As per claims 1-6, 9-12, 16-20, Rubino et al. teach an injectable composition comprising 25 mg/mL temsirolimus (CCI-779), dehydrated ethano, citric acid, d,I-α-tocopherol, and propylene glycol. See Example 2; claims.
Also, as per claims 1-13, 16-20, Rubino et la. Teach a diluent comprising 5% w/v polysorbate 80, 5% w/v polyethylene glycol 400, and water for injection. Rubino et al. teach this diluent can be preferably combined in a ratio of 9:1 v/v with the cosolvent concentrate of Example 1 or 2 to produce a solution of CCI-779 at a concentration of 2.5 mg/ml, which resulting mixture can be injected directly or further diluted with 0.9% Sodium Chloride Injection to provide a solution for intravenous injection. This diluent, when combined with the CCI-779 formulations in Examples 1 and 2, has been used to deliver doses of 0.5 to 500 mg CCi-779 via direct intravenous injection or intravenous infusion. See example 4, Claims.
Teaching of TORISEL PRODUCT LABEL
Torisel Product Label teaches Torisel (temsirolimus) injection, for intravenous infusion. See page 1.
Torisel injection, 25 mg/ml is supplied with diluent for Torisel. Torisel (temsirolimus) injection vial contents are first diluted with the enclosed diluent before diluting the resulting solution with 250 ml of 0.9% sodium chloride injection. See page 1, “Dosage and Administration”; page 1, “Dosage Forms and Strengths”.
As per claims 1-12, 17-20 in preparing the Torisel administration solution, Step 1 comprises injection 1.8 mL of DILUENT for TORISEL into the vial of TORISEL (temsirolimus) injection (25 mg/ml). the TORISEL (temsirolimus) vial contains an overfill of 0.2 ml (30 mg/1.2 ml). due to the intentional overfill in the TORISEL injection vial, the drug concentration of the resulting solution will be 10 mg/ml. a total volume of 3 ml will be obtained including the overfill. See page 3, 2.5 instructions for preparation and Administration.
As per claims 13-16, the required amount of temsirolimus from the 10 mg/ml drug solution/diluent mixture prepared in Step 1 is withdrawn and injected rapidly into a 250 mL container (glass, polyolefin, or polyethylene) of 0.9% sodium chloride injection. As the 10 mg/mL drug solution/diluent mixture has a volume of 3 mL, the maximum concentration of the resulting injectable composition is 0.12 mg/mL [30 mg in 250 mL 0.9% sodium chloride]. See page 3, 2.5 Instructions for Preparation and Administration.
As per claim 16, TORISEL (temsirolimus) injection comprises 25 mg/mL temsirolimus active ingredient and the inactive ingredients dehydrated alcohol (39.5% w/v), dI-alpha-tocopherol (0.075% w/v), propylene glycol (50.3% w/v), and anhydrous citric acid (0.0025% w/v). The DILUENT for TORISEL comprises the inactive ingredients polysorbate 80 (40.0% w/v), polyethylene glycol 400 (42.8% w/v), and dehydrated alcohol (19.9% w/v0. See pages 12-13.
Examiner’s Analysis and Conclusion of obviousness
A claimed invention is unpatentable if the difference between the claimed invention and the prior art are such that the claimed invention would have been obvious to one of ordinary skill in the relevant art. 35 U.S.C. § 103. Whether a claimed invention would have been obvious is a question of law, based on factual determinations regarding the scope and content of the prior art, differences between the prior art and the claims at issue, the level of ordinary skill in the pertinent art, and any objective indicia of non-obviousness. KSR Int’l Co.v. Teleflex Inc., 550 U.S. 398, 406 (2007); Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18(1966).
In KSR, the Supreme Court criticized a rigid approach to determining obviousness based on the disclosures of individual prior-art references, with little recourse to the knowledge, creativity, and common sense that an ordinary skilled artisan would have brought to bear when considering combinations or modifications. KSR, 550 U.S. at 415-22. Rejecting a blinkered focus on individual document, the court required an analysis that reads the prior art in context, taking account of “demands known to the design community,” “the background knowledge possessed by a person having ordinary skill in the art,” and “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418. This “expansive and flexible approach,” id. at 415, is consistent with the Courts’ pre-KSR decisions acknowledging that the inquiry “not only permits, but requires, consideration of common knowledge and common sense.” DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1367(Fed. Cir. 2006). As KSR established, the knowledge of such an artisan is part of the store of public knowledge that must be consulted when considering whether a claimed invention would have been obvious.
In recognizing the role of common knowledge and common sense, the Courts have emphasized the importance of a factual foundation to support a party’s claim about what one of ordinary skill in the relevant art would have known. See, e.g., Mintz v. Dietz & Watson, Inc., 679 F. 3d 1372, 1377 (Fed. Cir. 2012); Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F. 3d 1324, 1328 (Fed. Cir. 2009). One form of evidence to provide such a foundation, perhaps the most reliable because not litigation-generated, is documentary evidence consisting of prior art in the area.
Claim 1 requires an injectable composition comprising temsirolimus or a pharmaceutically acceptable salt thereof an a pharmaceutically acceptable excipient. Such a composition is taught by both Rubino et al. and Torisel Product label.
Claims 2-5 require the injectable composition is “suitable for” adventitial delivery in the leg (Claim 2), adventitial delivery below the knee (claim 3), adventitial delivery in the leg above the knee (claim 4), or adventitial delivery to a below-knee popliteal or tibial vessel (claim 5). As both Rubino et al. and Torisel Product Label teach injectable compositions comprising therapeutically effective amount of temsirolimus or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient suitable for direct injections, such compositions are clearly “suitable for” the recited uses.
Claims 6-8 require the therapeutically effective amount of temsirolimus is about 1 µg to 50 mg (claim 6), about 10 µg to 20 mg (claim 7), or about 25 µg to 10 mg (claim 8). Claims 9-10 require the injection volume of the composition is about 0.01 ml to about 50 ml (claim 9) or about 0.5 ml to about 20 ml (claim 10). Claims 13-15 require the concentration of temsirolimus is about 0.01 mg/ml to about 2.0 mg/ml mg/ml (claim 13), about 0.1 mg/ml to about 0.5 mg/ml (claim 14), or about 0.1 mg/ml to about 0.4 mg/ml (claim 15). Rubino et al. teach an injectable composition comprising 25 mg/ml temsirolimus (CCI-779) (Example 2) and teach a dilute can be preferably combined in a ratio of 9:1 v/v with the cosolvent concentrate of example 2 to produce a solution of CCI-779 at a concentration of 2.5 mg/ml, which resulting mixture can be injected directly. Rubino et al. teach this diluent, when combined with the CCI-779 formulation in Examples 1 and 2, has been used to deliver doses of 0.5 to 500 mg CCI-779 via direct intravenous injection or intravenous infusion. Torisel Product Label teaches Torisel injection, 25 mg/ml, is supplied with diluent for Torisel. Torisel teaches after dilution, the drug concentration of the resulting solution will be 10 mg/ml. Torisel teaches the required amount of temsirolimus from 10 mg/ml drug solution/diluent mixture prepared in Step 1 is withdrawn and injected rapidly into a 250 ml container (glass, polyolefin, or polyethylene) of 0.9% solium chloride injection. As the 10 mg/ml drug solution/diluent mixture has a volume of 3 ml, the maximum concentration of the resulting injectable composition is 0.12 mg/ml [30 mg in 250 ml 0.9% sodium chloride].
Claim 16 requires the pharmaceutically acceptable excipient is 0.9% sodium chloride injection USDP, dehydrated alcohol, dI-alpha tocopherol, anhydrous citric acid, polysorbate 80, polyethylene glycol 400, propylene glycol, or a combination thereof. Both Rubino et al. and Torisel product Lable teach combinations of the identical excipients claimed.
A person of ordinary skill in the art at the time the application was filed would have a reasonable expectation of success in formulating temsirolimus in an injectable composition suitable for adventitial delivery to a peripheral artery or direct injection to a vascular disease site because such injectable compositions were already well-known and commercially available at the time of Applicant’s filing. Indeed, Applicant used the commercially available temsirolimus injectable formulation Torisel in his only working example. See example 1.
Adjusting the final concentration of an injectable composition of temsirolimus using well-known and conventional pharmaceutical excipients for injection would have been well within the purview of a person of ordinary skill in the art the time the application was filed. Indeed, Rubino et al. teach diluting the CCI-779 formulations in Example 1 and 2 therein to deliver doses of 0.5 to 500 mg CCI-779 via direct intravenous injection or intravenous infusion. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claims are disclosed in the prior art, it is not invention to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
6. Claim Rejections - Obvious 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. See 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); and, In re Thorington, 418 F.2d 528, 168 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130 (b).
Effective January 1,1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-20 are rejected under the judicially created doctrine obviousness-type double patenting as being unpatentable over the claims 1-26 of US 10,576,063. Although the conflicting claims are not identical, they are not patentably distinct from each other because the current invention embraces the invention claimed in the above patent.
Determination of the scope and content of the prior art (MPEP §2141.01)
Claims 1-5, 17-20 are anticipated by claims 1, 7-14, 16-26 of the ‘063. Claims 6-8 are anticipated by claim 2 of the ‘063. Claims 9-10 are anticipated by claim 5 of the ‘063. Claims 11-12 are anticipated by claims 4 and 15 of the ‘063. Claim 16 is anticipated by claim 6 of the ‘063.
Respecting claims 13-15, which recite concentrations of temsirolimus, as the ‘063 recites therapeutically effective amounts of 1 mg to 50 mg (claim 2) and injection volumes of 0.01 mL to about 50 mL 9clai 5), the claimed concentrations (mg/mL) would have been prima facia obvious as concentrations clearly encompassed by the claimed therapeutically effective amount of 1 mg to 50 mg (claim 2) and injection volumes of 0.01 mL to about 50 mL (claim 5).
7. Claim Rejections - Obvious 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. See 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); and, In re Thorington, 418 F.2d 528, 168 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130 (b).
Effective January 1,1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-20 are rejected under the judicially created doctrine obviousness-type double patenting as being unpatentable over the claims 1-51 of US 10,617,678. Although the conflicting claims are not identical, they are not patentably distinct from each other because the current invention embraces the invention claimed in the above patent.
Determination of the scope and content of the prior art (MPEP §2141.01)
‘678 claims temsirolimus to treat analogues disease as the instant claims 1-20
Ascertainment of the difference between the prior art and the claims (MPEP §2141.02)
The difference between the instant claims 1-20 and the claims 1-51 of ‘678 patent is the claims are not word for word identical but the scope of the two sets of claims overlaps significantly with each other.
Finding of prima facia obviousness-rational and motivation (MPEP §2142.2143)
All the elements were known in prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Niloofar Rahmani whose telephone number is
571-272-4329. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor, can be reached on 571-272-8394. The fax phone number for the organization where this application or proceeding is assigned is 703-872-9306.
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/NILOOFAR RAHMANI/ Primary Examiner, Art Unit 1691
08/24/2026
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