DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Preliminary amendment filed on 02/12/2024 has been entered. Claims 1-17 are pending in this application. Claims 6-15 and 17 are withdrawn. Claims 1-5 and 16 are currently under examination.
Priority
This application is a 371 of PCT/KR2022/011480 filed on 08/03/2022 and claims foreign priority of KOREA, REPUBLIC OF 10-2021-0102394 filed on 08/04/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Election/Restrictions
Applicant's election without traverse of Group I invention (claims 1-5, 16, and 17) and species (A. Formula V:
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; and B. the injection preparation of claim 16) in the reply filed on 07/06/2026 is acknowledged. Claims 6-15 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1-5 and 16 are currently under examination.
Information Disclosure Statement
Three information disclosure statement (IDS) filed on 02/02/2024, 03/19/2025, and 07/07/2026 with appropriate assertion under 37 CFR 1.98 have been considered.
Claim Objections
Claims 1, 4, 5, and 16 are objected to because of the following informalities: In claim 1, insert the missing word “covalently” immediately before the recitation “bound” (line 2) because a chemical linkage is formed between the sugar and the amino group on the phthalimide moiety. In claim 4, 5, and 16, insert the missing phrase “lenalidomide or pomalidomide” immediately before the recitation “derivative” (line 2 of claims 4 and 5; line 1 of claim 16) to tie with the preceding lenalidomide or pomalidomide derivative, not sugar derivative. Appropriate correction is required.
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.
Claim 2 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 2 recites “derivative thereof”(line 3). However, the term “derivative” is not specifically defined and thus its scope is not clear. Applicant is advised to insert the word “structural” immediately before the above term “derivative” to set the scope of structural modification.
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.
Claims 1-3, 5, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (CN103421061, Dec. 4, 2013, provided with English translation for the citation here, hereinafter referred to as Xu ‘061, also listed in IDS filed on 02/02/2024).
With regard to structural limitations “a lenalidomide derivative in which a sugar or sugar derivative (or hexose; or glucose) is covalently bound to an amino group (NH2) on the phthalimide moiety of lenalidomide” (claims 1-3), and “an injection preparation comprising the lenalidomide derivative of claim 1 as an active ingredient” (claim 16):
Xu ‘061 disclosed a lenalidomide derivative compound of general formula I:
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wherein G-NH represents:
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. The synthesis route of 2,3,4,6-tetra-O-acetyl-1-deoxy-ß-D-glucopyranosyl glucose (G1-NH2) is as follows:
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. A pharmaceutical composition for treating diseases associated with angiogenesis, comprising a therapeutically effective amount of a compound of general formula I and a pharmaceutically acceptable carrier. The pharmaceutical composition may be a controlled-release tablet or capsule, an oral liquid, an injection (page 3/14, para. 3; page 5/14, para. 3; page 9/14, para. 2).
Thus, these teachings of Xu ‘061 anticipate Applicant’s claims 1-3, 5, and 16 and would also carry the same properties, including “50% or more improved water solubility compared to lenalidomide”, required by claim 5.
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.
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.
Claims 1-5 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kampmann et al. (Tetrahedron 71, 8140-8149, 2015, hereinafter referred to as Kampmann ‘2015) in view of Bahner et al. (Journal of Organic Chemistry 25, 2062-2063, 1960, hereinafter referred to as Bahner ‘1960).
With regard to structural limitations “a lenalidomide or pomalidomide derivative (or Formula III:
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or elected Formula V:
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) in which a sugar or sugar derivative (or hexose or pentose; or glucose or ribose) is covalently bound to an amino group (NH2) on the phthalimide moiety of lenalidomide or pomalidomide” (claims 1-4), and “an injection preparation comprising the lenalidomide or pomalidomide derivative of claim 1 as an active ingredient” (claim 16):
Kampmann ‘2015 disclosed a series of N-alkyl thalidomide analogues (5-18) containing substitution in the 4-position (similar to that of pomalidomide) or the 5-position. Synthesis of N-alkyl thalidomide analogues:
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.
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. A small amount of the imine intermediate was also isolated as expected, given the required three step reduction, Schiff-base condensation and reduction reaction sequence. All reactions were performed under argon unless stated otherwise. All solvents used in reactions were anhydrous (page 8141, left col., para. 3 and Table 1; page 8144, left col., para.2). The protein cereblon (CRBN), which is part of an E3 ubiquitin ligase, is one of the primary molecular targets of thalidomide (
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), lenalidomide (
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) and pomalidomide (
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). They have been used as a treatment for multiple myeloma, an as yet incurable form of bone marrow cancer (page 8140, right col., para. 1; left col., para. 1).
Kampmann ‘2015 did not explicitly disclose the limitations “a sugar or sugar derivative (or hexose or pentose; or glucose or ribose) is covalently bound to an amino group (NH2) on the phthalimide moiety” and “an injection preparation”, required by claims 1-5 and 16.
Bahner ‘1960 disclosed that 4-(4-Aminostyryl) quinoline (I) reacted readily with 4-dimethylaminobenzaldehyde to form a Schiff base that was less toxic than I. It seemed that aldose sugars might produce similar products (e.g.,
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) and that the sugar moiety might cause the compounds to be water soluble. The use of a small amount of dimethylformamide made it possible to bring the reactants into a homogeneous liquid reaction mixture at the desired temperature, 120-130°. Glyceraldehyde, ribose, galactose (II), glucose (III), lactose, and maltose all seemed to react smoothly under these conditions, but only II formed crystals that were purified readily by recrystallization. The other products tended to precipitate as gels or amorphous solids (page 2062, right col., para. 4).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the alkyl-aldehyde or alkyl-ketone reactant in anhydrous solvent as taught by Kampmann ‘2015 with the glucose or ribose reactant in aqueous solvent in view of Bahner ‘1960 to synthesize water-soluble glucose- or ribose-linked lenalidomide or pomalidomide because (a) the N-modification at the amino group (NH2) on the phthalimide moiety did not alter the compounds for targeting the CRBN protein and treatment of bone marrow cancers, and (b) the attachment of glucose or ribose, which contains aldehyde moiety, via Schiff base to the amino group improves water solubility, described above. Thus, one of skill in the art would have a reasonable expectation that by substituting the alkyl-aldehyde or alkyl-ketone reactant in anhydrous solvent as taught by Kampmann ‘2015 with the glucose or ribose reactant in aqueous solvent in view of Bahner ‘1960 to synthesize water-soluble glucose- or ribose-linked lenalidomide or pomalidomide, followed by selecting proper route of administration, such as injection for treating bone marrow cancers, one would achieve Applicant’s claims 1-5 and 16. "Exemplary rationales that may support a conclusion of obviousness include: (B) Simple substitution of one known element for another to obtain predictable results". See MPEP § 2143 [R-01.2024] [I]. "[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 MPEP § 2144.05 [R-01.2024] [II.A].
The lenalidomide or pomalidomide derivative of Kampmann ‘2015 in view of Bahner ‘1960 meets all structural limitation of claimed lenalidomide or pomalidomide derivative and would carry the same properties, including “50% or more improved water solubility compared to lenalidomide”, required by claim 5.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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