DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/26/2026 has been entered.
The rejection under section 103 is withdrawn in favor of the following new ground of rejection. Namely, Applicant argues that Balan and Khalili each show PEGylated antibodies. The antibodies are not combined with a drug molecule as in ADCs. The aim of Balan is to PEGylate antibodies to improve yield and purification (e.g., Abstract of Balan). No mention whatsoever is made of combining a PEGylated antibody with a drug molecule, as would be required to create an ADC. Thus, one skilled in the art would not have applied the alleged teachings of Balan and Khalili to the field of ADCs.
Moreover, Applicant has amended claim 14 to groups containing PEG, limiting the PEG is no more than 2 kDa in weight. In this regard, Balan and Khalili are concerned with groups containing PEG chains that are large. In contrast, present claim 14 is limited to groups containing PEG, wherein the PEG is no more than 2 kDa in weight. In the first column of page 65 of Balan it is explained that "PEG with linker subunit was constructed as a linear chain comprising 230 monomers (10 kDa)." The "Materials" section of page 62 also lists the PEG reagent as having a mass of 10 or 20 kDa. Similarly, the final sentence of column 2, page 2268 of Khalili explains that conjugates with 20, 30 and 40 kDa PEG were studied, and the Abstract explains that PEG reagents of 10-40 kDa were investigated. Thus, the core of Balan and Khalili is to attach large PEG groups to antibody fragments. There is no teaching of a PEG that has a weight of no more than 2 kDa. For this additional reason, one skilled in the art would not have arrived at an ADC that can be prepared by the process of present claim 14.
The rejection below now includes BADESCU et al. "Next generation protein-drug conjugates" PolyTherics poster presented at Bio2011, all pages (Oct 25-28, 2011). The reference clearly demonstrates a PEGylated antibody prepared with the same reagent required by the instant claims to create an ADC, with a PEG component with the recited size:
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 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, 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.
Claims 14, 25, 29, 30, 33-47 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Badescu et al. "Next Generation Protein-Drug Conjugates" PolyTherics poster presented at Bio2011, (Oct 25-28, 2011), newly cited (Badescu) in view of
U.S. Patent No 7,994,135 to Doronina et al., previously cited (Doronina); or
Doronina et al., Nature Biotechnology (2003), 21(7), 778-784, previously cited (Doronina II).
Badescu teaches the instant conjugation methods with a reagent of formula (VIII):
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320
332
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The reagent provides the instant disulfide 3-carboin bridge:
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66
548
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The methods specifically can prepare ADC’s:
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376
424
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192
560
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The PEG moiety is typical of those used in ADC’s:
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106
200
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Badescu may not explicitly teach the specific linker-payloads required by the claims, i.e., Val-Cit-PAB-MMAE.
However, these linker-payload groups were a common motif in ADC’s. It is for that proposition that the rejection joins the Doronina references:
Doronina teaches antibody drug conjugate of Trastuzumab-MC-vc-PAB-MMAE (columns 49-50) (Antibody-maleimidocaproyl-val-cit-para-aminobenzyloxycarbonylmonomethylauristatin F). Doronina teaches amino acid spacer units that can be used as linkers which include alanine and valine in the table list (column 65, lines 15-50).
Doronina II demonstrates that the MC-Val-Cit-PAB-MMAE conjugate was well known in the art:
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592
684
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In this way, those of ordinary skill could have applied the recited linker-payloads in the manner required and in a predictable fashion for the purposes of obtaining the recited conjugates. As outlined above, Badescu teaches the instant antibody conjugation methods with a reagent of formula (VIII). The Doronina references are added for the proposition that conjugating Val-Cit-PAB-MMAE in this manner is applicable to this methodology. Specifically, Doronina demonstrates that this linker-payload in ADC’s was recognized as ubiquitous in the art. In this manner, those of ordinary skill would have recognized that applying the conjugation technique of Badescu to this linker-payload would have yielded predictable results. Accordingly, applying the instant conjugation technique to Val-Cit-PAB-MMAE to prepare the instant ADC’s would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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