DETAILED ACTION
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 .
Applicant’s amendment and remarks filed on 12/15/2025 are acknowledged. Claims 30-31 are amended. Claim 32 is cancelled. Claims 20-31 and 33-37 are pending and are currently under examination.
Specification Objection Withdrawn
The objection to the disclosure because it contains an embedded hyperlink is withdrawn in light of applicant’s amendment thereto.
Claim Objections Maintained
Claim 24 is objected to because of the following informalities: The claim contains the acronym MMAE. While acronyms are permissible shorthand in the claims, the first recitation of the term should include the full recitation followed by the acronym in parentheses. Appropriate correction is required.
Applicant has not addressed this objection.
Claim Rejections Withdrawn
The rejection of claim 32 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn. The cancellation of the claim renders the rejection moot.
The rejection of claims 30-31 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention is withdrawn in light of applicant’s amendment thereto.
The rejection of claim 32 under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn. The cancellation of the claim renders the rejection moot.
Claim Rejections Maintained
35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The rejection of claims 20-31 and 33-37 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for the reasons set forth in the previous office action. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to methods of treating T cell lymphoma or leukemia by administering an antibody conjugate that binds to TRBC and which has a dissociation rate constant between 0.001 and 0.3 s-1. For dependent claims, the antibody must bind specifically to TRBC1 or TRBC2. Some claims require specific mutations with reference to either SEQ ID NO:1 or SEQ ID NO:2. The claimed structures are limited only in that they must have the required binding and dissociation constant and that they must be antibodies or antibody fragments. While some claims do have specific mutations, these claims state that the antibodies comprise these mutations. Therefore, there is no limit to the mutations that can be made.
The specification discloses antibodies with the VH and VL of SEQ ID NO:1 and 2 and several variants of these with specific point mutations. Not all of these mutations actually fit the required dissociation constant (see, for example, G31S).
The functional characteristics of antibodies (including binding specificity and affinity are dictated by their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Other than the specific antibodies with the disclosed VH and VLs described in the specification, applicant has not described any antibodies that have the required function and have provided no description or guidance as to what structural features will provide the required function.
The specification discloses only limited species within the instant claims scope and does not provide any guidance as to which amino acids can be varied while retaining the appropriate binding activity.
Therefore, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Applicant argues:
That the application demonstrates the anti-TRBC1 antibody Mut11 and the anti-TRBC2 antibodies KFN and Mut15 have lower affinities but improved internalization. The provided amino acid sequences of those antibodies would be understood by the skilled person to provide a structural basis for generating additional antibodies with affinities recited in the claims. Applicant further submits that at least specification page 16, line 19 through page 20, line 12 provide structural information relating to TRBC binding useful in the claimed methods.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
Applicant’s argument is noted but does not address or counter the issues raised in the rejection.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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