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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/1/2025 has been entered.
Claims 67-73, 77-86, and 90-94 are now pending. Claims 67, 81, 90, and 91 are amended. Claims 70-72, 81-86, and 90-92 remain withdrawn. Claims 93 and 94 are new. Claims 67-69, 73, 77-80, 93 and 94 are currently under prosecution.
Maintained Rejection
(Arguments Addressed)
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 67-69, 73, 77-80, 93 and 94 remain rejected 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. 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method for treating an aggressive cancer comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment thereof specifically binds to an integrin alpha10 polypeptide, and the aggressive cancer is aggressive breast cancer, wherein the antibody is or antigen-binding fragment is capable of binding specifically to the extracellular I-domain of the integrin alpha10 polypeptide chain. Dependent claim 93 recites that that the monoclonal antibody, produced by the hybridoma cell line deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the accession number DSM ACC2583;
Thus, the claims identify the antibody that binds to an integrin alpha10 polypeptide by function only, where the function is to (1) bind to the extracellular I-domain of integrin alpha 10 polypeptide, (2) treat aggressive cancer, (3) capable of inducing cell death and/or inhibiting growth, (4) inhibiting proliferation, and/or (5) inhibiting migration of cells expressing an integrin alpha10 polypeptide. No structure of the antibody is recited.
With regards to the antibody that binds to an integrin alpha 10 polypeptide, the instant specification recites the following:
[0412] The antibody of the present invention defined by the amino acid sequences of SEQ ID NO.s: 4-11, will hereby be denoted Th101. The Th101 antibody is disclosed herein by its 6 CDRs (complementary determining regions) (SEQ ID NO: 4 to 9), by its heavy chain variable region (SEQ ID NO: 10) and by its light chain variable region (SEQ ID NO: 11). The identification and production of the Th101 antibody, as employed in the examples, is described in WO 08/075038, included herein by reference.
The specification also teaches the mAb 365 hybridoma cell line deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH under the accession number DSM ACC2583) also named mAbα 10 (=Ab365), which is the elected species. See ¶¶ [0406] and [0745]. These antibodies bind to different epitopes of Integrin Alpha 10. See Example 12.
Thus, the instant specification describes two antibodies, Ab365 and Th101, that binds to an integrin alpha 10 polypeptide that treat an aggressive cancer as claimed. The specification fails to disclose sufficient structural sequence information required of an antibody that binds to integrin alpha 10 polypeptide to possess the function of (1) bind to an integrin alpha 10 polypeptide, (2) treat aggressive cancer, (3) capable of inducing cell death and/or inhibiting growth, (4) inhibiting proliferation, and/or (5) inhibiting migration of cells expressing an integrin alpha10 polypeptide.
The structure activity relationship of the CDR antigen binding region that binds integrin alpha 10 polypeptide is not known and the binding epitopes cannot be predicted based on the antibody sequences.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibodies that function as listed (1)-(5) above, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for antibodies that bind an integrin alpha10 polypeptide and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. An integrin alpha 10 polypeptide provides no information about the structure of an antibody that binds to it.
The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses only a single exemplary antibody sequence that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. The specification fails to provide any structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequences for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
Given the lack of representative examples to support the full scope of the claimed antibodies used in the claimed method, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide integrin alpha10 polypeptide binding and treating function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that bind to an integrin alpha10 polypeptide, or possess the functions listed above in (1)-(5) that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner’s Suggestion: Amend claim 67 to recite the structure critical to the antibody that binds to the extracellular I-domain of the integrin alpha 10 polypeptide, that is the antibody comprising all six heavy and light chain CDR SEQ ID Nos: 4-9 (limitations of claim 94)
Response to Arguments
Applicant amended claim 67 to recite that “that the antibody or antigen-binding fragment is capable of binding specifically to the extracellular I-domain of the integrin alpha10 polypeptide chain.” Applicant submits Declaration of Dr. Evy Lundgren-Akerlund and states that three different representative therapeutic antibodies exemplified in the application that are capable of binding specifically to the extracellular I-domain of the integrin alpha-10 polypeptide: mAbα10, Th101, and “alternative mouse monoclonal anti-integrin alpha 10 antibody. Applicant argues there is a correlation between the function and the structure and that the claimed methods should not be limited to any particular integrin alpha10 antibody, much less limited to any specific 6 CDRs. Applicant argues that integrin alpha 10 antibodies are known in the art.
Applicant’s arguments have been considered but are not persuasive. Two specific examples and an “alternative mouse monoclonal anti-integrin alpha 10 antibody” does not provide full scope of the claimed method.
By the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3. Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
Thus, the structure of the antibody is necessary in order to determine the function of the antibody. Other than commercial antibodies, a search of the prior art does not provide any examples of integrin alpha-10 antibodies used to treat cancer. Thus, integrin alpha-10 antibodies are not known in the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600