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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 31, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-8 are currently pending and subject to examination.
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.”
Claims 1-5 and 7 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 1 includes an optional step. It is unclear if this step is intended to further limit the method of claim 1. Therefore, one of ordinary skill in the art cannot determine the metes and bounds of the claim.
Claim 7 defines the crystalline form of lenalidomide by reference to Figures. As stated in MPEP 2173.05(s):
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Appropriate correction is required.
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 6-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gore et al. (US 8,946,265 B2, published Feb. 3, 2015).
Claim 6 is directed towards lenalidomide (I) as anhydrous crystal form SRA characterized by having:
a water content of 0.1-0.5%;
XRPD peaks at 7.7, 11.2, 14.2, 15.6, 19.9, 20.3, 23.9, 25.7, 28.2, 32.3, 33.4 + 0.20 2θ;
IR absorption spectral peaks at 3410 cm-1, 3347cm-1, 2962 cm-1, 2912 cm-1, 1642 cm-1, 1607cm-1, 1452cm-1, 1411 cm-1, 1209 cm-1, 1163 cm-1;
DSC endothermic peak ranging between 265 to 270 °C.
Gore teaches an anhydrous crystal form of Lenalidomide (I)
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(Gore, Fig. 1), having an XRPD diffraction pattern as instantly claimed:
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Gore, Fig. 2.
Compare with instant Fig. 1:
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Instant Fig. 1.
The instantly claimed polymorphic form is substantially identical to Gore’s polymorphic form as demonstrated by the above XRPD patterns.
Gore also discloses a DSC peak at 269 °C:
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Gore, Fig. 3.
Gore also discloses a chemical purity of greater than 99.9% as measured by HPLC (Gore, Specification, col. 3, lines 19-20). While Gore does not teach the water content, Gore teaches that the crystal form is anhydrous and unsolvated, non-hygroscopic, and thermodynamically stable (Gore, Specification, col. 5, lines 58-61), and thus is presumed to have minimal moisture content as instantly claimed.
While Gore does not disclose the IR spectrum, the crystal of Gore appears substantially identical to the instantly claimed crystal and is therefore inherently presumed to have the same IR spectrum.
Therefore, claim 6 is anticipated.
Claim 7 recites: 3-(4-amino-l-oxoisoindolin-2-yl) piperidine-2, 6-dione or Lenalidomide (I) crystalline Form SRA as claimed in claim 6, characterized by X-ray powder diffraction pattern according to FIG. 1, TGA Thermogravimetric analysis according to FIG. 3, IR absorption spectrum according to FIG. 4, DSC isothermal pattern according to FIG. 5 and High performance Liquid chromatographic purity according to FIG. 6.
The rejection of claim 6 is incorporated herein by reference with regards to XRPD spectrum, HPLC purity and DSC isothermal pattern.
Furthermore, the TGA analysis is substantially identical:
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Gore, Fig. 4.
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Instant, Fig. 3.
Therefore, claim 7 is anticipated.
Claim 8 recites: “3-(4-amino-l-oxoisoindolin-2-yl) piperidine-2, 6-dione or Lenalidomide (I) crystalline Form SRA as claimed in claim 6 having purity of greater than 99.9% (area % by HPLC).” Gore also discloses a chemical purity of greater than 99.9% as measured by HPLC (Gore, Specification, col. 3, lines 19-20). Therefore, claim 8 is anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
“A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.”
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gore et al. (US 8,946,265 B2, published Feb. 3, 2015), as applied to claims 6-8 above, and further in view of Devarakonda et al. (US 2011/0021567 A1, published Jan 27, 2011).
The rejection of claims 6-8 under 35 U.S.C. 102(a)(1) is incorporated herein by reference, as such these claims were prima facie obvious at the time of filing.
Claim 1 is directed towards a process of preparing the lenalidomide crystal form SRA comprising the steps of:
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Claim 1.
Gore teaches the reaction of (a) and (b) in the presence of triethylamine and dimethylformamide to produce (c):
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Gore, Specification, col. 14.
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Gore teaches reacting (c) with hydrogen gas at a temperature of 30-35 °C and normal atmospheric pressure in the presence of palladium carbon catalyst to get lenalidomide (I):
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Gore, Specification, col. 14-15.
While Gore teaches that the medium has a moisture content of about 50%, one of ordinary skill in the art would have a reasonable expectation of success to use an anhydrous medium because it is commonly known in the art that water is optional. For example, Devarakonda teaches that the reaction can be carried out using palladium on carbon in 1,4-dioxane solvent, using 10% palladium on carbon in methanol, using 10% palladium on carbon in a mixture of solvents comprising methanol and N,N-dimethylformamide (Devarakonda, Specification, paragraphs 7-9). Devarakonda teaches a specific example with an anhydrous medium:
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Devarakonda, Specification, paragraphs 161-162.
Gore teaches a purification step comprising combining compound (I) with an acid in the presence of an aliphatic alcohol solvent at ambient temperature for 45 minutes:
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Gore, Specification, col. 15.
Gore teaches that the acid can be organic such as those resulting in the acetate, tartrate, oxalate, malate and fumarate salts, and inorganic acids such as hydrochloric acid or sulphuric acid (Gore, Specification, col. 10, lines 7-11). While Gore does not teach methanesulfonic acid, one of ordinary skill in the art would have a reasonable expectation of success to use methanesulfonic acid because it is commonly known in the art that lenalidomide can also form an salt with methanesulfonic acid for further purification. For example, Devarakonda teaches lenalidomide methansulfonate salt (Devarakonda, Specification, paragraphs 161-162).
One of ordinary skill in the art would have a reasonable expectation of success to obtain crystal form SRA as in claim 1 because Gore teaches that purified lenalidomide can be obtained by reacting lenalidomide with an organic acid dissolving in a C1-C5 alcohol and then liberating the purified lenalidomide base with a secondary or tertiary alkyl amine such as triethylamine:
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Gore, Specification, col. 10.
One of ordinary skill in the art would have a reasonable expectation of success to isolate the crystal form SRA because Gore teaches isolation of crystal form SRA:
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Gore, Specification, paragraph 13.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claim 2 is directed towards the process of claim 1, wherein the organic amide is selected from N,N-dialkyl (C1-C4) amide. As shown in the rejection of claim 1, Gore uses dimethylformamide which is a N,N-dialkyl (C1-C4) amide. Therefore, claim 2 was prima facie obvious at the time of filing.
Claim 3 is directed towards the process of claim 1, wherein the hydrogenation takes place via hydrogen gas bubbling at normal atmospheric pressure. As shown in the rejection of claim 1, Gore teaches hydrogen gas bubbling at normal atmospheric pressure. Therefore, claim 3 was prima facie obvious at the time of filing.
Claim 4 is directed towards the process of claim 1, wherein the organic acid is selected from citric acid, tartaric acid, lactic acid or malic acid. As shown above in the rejection of claim 1, Gore teaches acetic, tartaric, oxalic, malic and fumaric acids. Therefore, claim 4 was prima facie obvious at the time of filing.
Claim 5 is directed towards the process of claim 1, wherein the alkylamine used in step iv) is selected from triethylamine, diisopropyl amine or diisopropyl ethyl amine. As shown in the rejection of claim 1, Gore teaches that the alkylamine is preferably triethylamine. Therefore, claim 5 was prima facie obvious at the time of filing.
Joint Inventors
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629