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 .
DETAILED ACTION
Application status
Claims 1-2, 4-5, 7-10, 12, 15-16, 18-19, 21-22, 25-26, 28-29, 36 and 56 are pending in this application.
Priority
The instant application is the 371 national stage entry of PCT/US2021/030187, filed on 04/30/2021, which claims benefit of 63/018233 filed on 04/30/2020.
Election
Applicant's election without traverse of Group I, Claims 1-2, 4-5, 7-10, 12, 15-16, 18-19, 21-22, 25-26 and 28-29, and species: MMAE in the response filed on 11/26/25, is acknowledged.
Claims 36 and 56 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/01/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim 5 recites the limitation "recombinant human serum albumin" in claim 1. There is insufficient antecedent basis for this limitation in the claim. The Examiner suggests replacing the noted phrase with “recombinant human albumin”.
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 1-2, 4, 7, 16, 18-19, 21, 25-26 and 29 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Mehtala et al. (Cys34-PEGylated Human Serum Albumin for Drug Binding and Delivery, Bioconjug Chem. 2015 May 20; 26(5): 941–949, see IDS).
The instant claims are drawn to a composition comprising an albumin drug conjugate wherein the albumin is recombinant human albumin, wherein the drug and recombinant human albumin are conjugated ex vivo.
Mehtala et al. teach a composition comprising an albumin drug conjugate wherein the albumin is recombinant human albumin, wherein the drug is paclitaxel, which belongs to the class of chemotherapeutic drugs known as taxanes, and wherein the recombinant human albumin is covalently conjugated ex vivo at Cys-34 via a maleimide linker comprising 5- or 20-kDa mPEG spacer (see abstract, “MATERIAL AND METHODS” ON pages 7-10, Scheme 1 on page 23), thereby anticipating claims 1-2, 4, 7, 18-19, 21, 25-26 and 29. Mehtala et al. further teach that the albumin and drug-linker conjugate are conjugated at a molar ratio of 1:5 (see Figure 9 (b)) thereby anticipating claim 16.
Therefore, teachings of Mehtala et al. anticipate Applicants’ claimed invention.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 4-5, 7-10, 12, 15-16, 18-19, 21-22, 25-26 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Mehtala et al. (Cys34-PEGylated Human Serum Albumin for Drug Binding and Delivery, Bioconjug Chem. 2015 May 20; 26(5): 941–949, see IDS) in view of Kim et al. (US Patent No. 9775914), Bradbury et al. (US Patent No. 10548989), an evidentiary reference of Buckel et al. (Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery, Cancer Res. 2015 April 1; 75(7): 1376–1387), and KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007).
The instant claims are drawn to a composition comprising an albumin drug conjugate wherein the albumin is recombinant human albumin, wherein the drug and recombinant human albumin are conjugated ex vivo.
The teachings of Mehtala et al. are as described above. Mehtala et al. further teach that [1] recombinant human albumin is at a concentration of 25 mg/mL (see page 3 under “Synthesis and Characterization of PEGylated HAS adducts”); and [2] drug to albumin ratio is 10:1 (see Table 1 on page 24);
Mehtala et al. do not teach the use of a cleavable linker, MMAE as a drug, recombinant human albumin concentrations of 5 mg/mL to 15 mg/mL, and drug to albumin ratios of 1:1 to 3:1.
Kim et al. teach a chemotherapeutic prodrug conjugate comprising: an albumin-binding moiety such as maleimide, which is joined through a caspase 3-cleavable peptide linker, which is conjugated to a chemotherapeutic agent selected from anthracyclines, antibiotics, alkylating agents, platinum-based agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, doxorubicin, daunorubicin, epirubicin, idarubicin, valrubicin, actinomycin-D, bleomycin, mitomycin-C, calicheamicin, cyclophosphamide, mechlorethamine, uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, thiotepa, altretamine, duocarmycin, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, triplatin tetranitrate, 5-fluorouracil, 6 mercaptopurine, capecitabine, cladribine, clofarabine, cystarbine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, pemetrexed, pentostatin, thioguanine, camptothecin, topotecan, irinotecan, etoposide, teniposide, mitoxantrone, paclitaxel, docetaxel, izabepilone, vinblastine, vincristine, vindesine, vinorelbine, estramustine, maytansine, DM1 (mertansine), DM4, dolastatin, auristatin E, auristatin F, monomethyl auristatin E, monomethyl auristatin F (boldfaced for added emphasis) (see claims 1-3 and 8-11 of ‘914 patent), thereby reading Applicants’ claims 8, 10, 12 and 28.
Bradbury et al. teach a cathepsin-B cleavable valine-citrulline dipeptide linker (see column 19, lines 13-15), thereby reading on claim 15.
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to make and use the composition comprising an albumin drug conjugate as taught by Mehtala et al. and replace the drug from paclitaxel to another chemotherapeutic drug MMAE while using many cleavable linkers taught by Kim et al. and Bradbury et al. A POSITA would have been motivated to make and use such composition because [1] MMAE is much more potent than paclitaxel as a chemotherapeutic drug as evidenced by Buckel et al. (see the direct comparison of IC50 between MMAE and paclitaxel in Figure 1D, and also abstract); and [2] cleavable linkers provide site-specific payload release within tumor cells, thereby reducing toxic effects on normal cells that are neighboring cancer cells.
Claims 5 and 22 are included in this rejection in accordance with MPEP 2144.05 “Optimization & Result Effective Variables”. It discusses that result-effective variables can be optimized, especially when a particular parameter is recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation. In the instant case, Mehtala et al. teach that [1] recombinant human albumin is at a concentration of 25 mg/mL (see page 3 under “Synthesis and Characterization of PEGylated HAS adducts”); and [2] drug to albumin ratio is 10:1 (see Table 1 on page 24), which can be optimized for different chemotherapeutic drugs with different potencies, which is the case between MMAE and paclitaxel. Therefore, the use of human albumin is at a concentration of 5 mg/mL to 15 mg/mL as well as the use of the molar ratio of drug to albumin is 1:1 to 3:1 would have been obvious to one of ordinary skill in the art as being result effective variables, and would be characterized as routine experimentation.
A POSITA would have had a reasonable expectation of success to make and use such composition because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Mehtala et al., Kim et al. and Bradbury et al prior to the filing of the instant application.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Examiner Note:
The reference of JP 2017506628 A is noted herein because this reference also teaches a prodrug conjugate comprising albumin to MMAE via covalent bond (see claims).
Conclusion
Claims 1-2, 4-5, 7-10, 12, 15-16, 18-19, 21-22, 25-26 and 28-29 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656