Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim 1 is pending and under examination.
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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claim 1 is rejected under 35 U.S.C. 103(a) as being unpatentable over Wu et al. (Protein Eng. 2001 Dec;14(12):1025-33) in view of Withoff et al. (Br J Cancer. 2001 Apr 20;84(8):1115-21), as evidenced by Hexham et al. (Molecular Immunology 38 (2001) 397–408) (all cited herewith).
Wu teaches the production of single-chain anti-CD20 antibodies by fusing single-chain Fv (scFv) with human IgG1 hinge and Fc regions, designated scFv-Fc (see Abstract). In the final paragraph of their Discussion Wu concludes:
“chimeric single-chain form of an anti-CD20 antibody (scFv-Fc) has been produced with properties suited for further development as an immunotherapeutic for B-cell leukemias and lymphomas, including retention of antigen binding and high complement-dependent cytolytic activity” (emphasis added); however, their scFv-Fc also “demonstrated a strong
propensity to multimerize” and “…investigation of the residues that interact at the VL-VH interface or framework residues that affect folding rates, may provide insight into the dynamic process of assembly of these multimers. Alternately, strategies such as…modifying hydrophobic residues that are exposed at the base of the Fvs, in this type of construct may favor formation
of a stable monomeric form.”
Withoff teaches the production of a bispecific anti-C20xCD3 antibody, “BIS20x3,” via “hybrid hybridoma fusion” wherein a “quadroma cell line producing BIS20x3 was made by fusion of
B-ly1 and CLB-T3/4.2B” hybridoma cell lines (see page 1117, right col., 1st full paragraph) and with respect to the possibility of unwanted heavy/light chain combination, Withoff teaches the following:
“Although it is theoretically possible that our quadroma produces up to 10 different immunoglobulin molecules due to shuffling of the heavy and light chains (Kroesen et al, 1998), our purified product is very efficient in retargeting T-cells to B-cells (Figure 4). This was expected because in general the percentage of unwanted heavy/light chain combinations is low because each heavy chain has the highest affinity for its own light chain. Moreover, the most
important and most abundant ‘contaminants’, the parental monospecific species, were certainly not isolated (see Figure 1)….”
Figure 1 is reproduced below for reference:
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While the Withoff does not explicitly teach that their BIS20x3 producing hybrid-hybridoma fusion does not produce the unfavorable multimers that are produced during production of the scFv-Fc of Wu, given the apparent stability associated with the heavy and light chain variable domain pairing of the B-ly1 antibody of Withoff it would have been obvious to one of ordinary skill in the art that this particular anti-CD20 antibody is well suited for the production of the scFv-Fc of Wu.
Thus, one of ordinary skill in the art would have been motivated to make use of nucleic acids encoding the heavy and light chain variable domains of the murine anti-CD20 antibody B-Ly1 from Withoff to clone an scFv-Fc as described by Wu.
A reason the ordinarily skilled artisan would have been motivated to clone the nucleic acids encoding the heavy and light chain variable domains of the murine anti-CD20 antibody B-Ly1 from Withoff for use in producing the scFv-Fc described by Wu was because the ordinarily skilled artisan would have had a reasonable expectation of successfully using such nucleic acids to produce a more stable form of the scFc-Fc of Wu given the apparent stability associated with the heavy and light chain variable domain pairing of the B-ly1 antibody described by Withoff.
Note that the teachings of Withoff tend to indicate the hybridoma producing the B-Ly1 antibody would have been readily available to one of ordinary skill in the art as of applicant’s date of invention. Thus, using techniques well known to one of ordinary skill in the art (see, e.g., Hexham for one example of how this can be done at page 398-99 page bridging paragraph to page 399, 1st full paragraph), it would have been a trivial matter to clone the Vh and Vl domains of the B-Ly1 antibody thereby obtaining the sequences recited in claim 1.
In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY S SKELDING whose telephone number is (571)272-9033. The examiner can normally be reached M-F 9-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY S SKELDING/Primary Examiner, Art Unit 1644
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