DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 3-7, 11, 13, 15, 17, 20-24, 29-30, 32, 36, 44 are pending and are under examination.
Claims 1 is objected to for the following informalities: the claim recites that the VH domain comprises “the heavy chain complementary determining region (CDR) 1”, “a CDR2”, and “a CDR3”. The use of “the” and “a” is inconsistent, correction is required.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-7, 11, 13, 15, 17, 20-22, 24, 36, are rejected 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is directed to a monoclonal antibody comprising CDR1-3 SEQ ID NO: 1 and 5. The scope of the actual residues encompassed by the instant claims is unclear and indefinite, since different numbering schemes exist for defining CDR residues, and the instant specification does not define the metes and bounds of the claimed CDRs. The specification discloses exemplary embodiments wherein the CDRs can be per Kabat or IMGT, and discloses exemplary CDRs, such as, for example, CDRs of SEQ ID NO: 2-4 and 6-8. However, these examples are not a sufficient definition of the claim scope. For example, would claim 1 encompass CDRs as defined by other number schemes, and which ones? Would the claim encompass an antibody with a mixtures of CDRs from different numbering schemes? The scope of the claims is unclear and indefinite.
Claim 7 is indefinite since it recites that the antibody is a “human” antibody. The VH and VL of SEQ ID NO; 1 and 5 are murine, and it is unclear how an antibody requiring murine CDRs could be considered a “human” antibody.
Claim 21 is indefinite in the recitation of a vector “encoding” the nucleic acid molecule. Vectors typically comprise nucleic acids, which would encode an amino acid sequence. Do the claims mean encoding an amino acid sequence? Or are the claims intended to be directed to a vector comprising the nucleic acid molecule.
The scope of the method claimed in claim 44 is unclear and indefinite. The claim is directed to a method of increasing an immune response in a subject “being treated with an antibody specific for MCT11” comprising administering an immunotherapy to the subject. The only active step is administering an immunotherapy, and It is unclear what type of subjects are encompassed. For example, does the method require a subject who is receiving MCT11 at the same time as the immunotherapy? Would the claims encompass subjects previously treated with MCT11, and if so how long ago?
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.
Claim(s) 23, 29-30, and 32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20190000947 (of record).
The ’947 publication teaches a method of treating cancer comprising administering to a subject an monoclonal antibody that binds to the protein product of SLC16A11, i.e. MCT11 (see Table 1, paragraphs 317, 378-380, 409, 411, 421, 423 and 424 in particular). The ‘947 publication teaches that the antibody can be used in combination with other therapies. The method would inherently reduce T cell exhaustion or increase effector function of T cells, since it is identical to the claimed method. Claim 32 is rejected to the extent that the immunotherapy is optional. For example, if claim 32 were incorporated into claim 30, the claim would be directed to a method of treatment wherein the subject has cancer or is receiving an immunotherapy, wherein the immunotherapy comprises TIL. In other words, the claim recites a type of immunotherapy but does not require treatment with immunotherapy.
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.
Claims 29-30 and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20190350938 (of record), in view of US 20140286906.
The ‘938 publication teaches a method of treating type 2 diabetes in a subject comprising administering to the subject an antibody that binds to SCL16A11 polypeptide (i.e. MCT11, see paragraph 23, in particular). The ‘938 publication teaches administration in combination with other therapeutics useful for treating of diabetes (see paragraph 198, in particular).
The reference differs from the claimed invention in that it does not explicitly teach administering an immunotherapy or increasing an immune response.
The ’906 publication teaches a method of treating type 2 diabetes comprising administering an immunomodulatory IGF-1 agent (i.e. an immunotherapy) wherein the IGF increase T reg activity (i.e. increases an immune response).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further administering the immunomodulatory immunotherapy of the ‘906 publication, as the combination therapeutic in the method of treatment of the ‘938 publication. The ordinary artisan at the time the invention was made would have been motivated to do so to increase therapeutic treatment of diabetes.
Claims 23, 29-30, 32, and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20190000947, in view of Marin-Acevedo, 2018.
The teachings of the ‘947 publication are described above.
The reference differs from the claimed invention in that it does not explicitly teach administering an immunotherapy.
Marin-Acevedo teaches that combination therapies for cancer will better boost the anti-tumor immune response, and that various immunotherapies, such as CAR T cells can be used to treat cancer.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further administer an immunotherapy such as CAR T cells, in the cancer treatment method of the ‘947 publication. The ordinary artisan at the time the invention was made would have been motivated to do so since Marin-Acevedo teaches that combination therapies for cancer will better boost the anti-tumor immune response.
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.
Claims 23, 29-30, 32 and 44 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of antibodies specific for MCT11.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The instant claims are directed to a method of increasing an immune response, a method of treating cancer, and a method of reducing T cell exhaustion employing an antibody specific for MCT11, or a nucleic acid encoding said antibody. The claims encompass methods employing a broad genus of structurally different antibodies and nucleic acids. For example, the claims would encompass polyclonal or monoclonal antibodies, or fragment thereof, derived from different species, such as human, mouse, or rat that would have different VH and VL sequences. Furthermore, the claims encompass a genus of antibodies that bind to different epitope regions of MCT11, or those with different affinities or pharmokinetic properties. The claims recite that the antibodies function to bind to MCT11, to treat cancer and/or reduce T cell exhaustion or increase an immune response. The state of the art is such that antibody based therapy is extremely complex and requires a deep understanding of protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system. Antibodies can function as depleting antibodies by ADCC, as agonist or antagonists, and can modulate the immune system directly. Furthermore, the development of candidate antibodies involves a complex process of clinical and preclinical evaluation that include identification of the physical and chemical properties of the antibody (see Scott et al, pages 278-279, of record). Antibodies have a wide range of pharmacokinetics, effector functions, size and immunogenicity, affinities and avidities, all of which effect the function of each antibody in vivo (see Scott et al., 2012, page 278, in particular).
The state of the art is such that antibody variable regions are composed of a heavy and light chain, each involved in providing for binding specificity. Variability in the antigen binding site is achieved by V(D)J recombination via heavy and light chain pairing, with the most diverse regions being the 6 CDR regions in the heavy and light chain. See Janeway, which teaches that the antibody repertoire in humans is at least 1011, with a large degree of diversity in both heavy and light chains. See, also Rabia, 2018, which teaches that the maximal chemical diversity of antibody CDRs is unimaginably large and is extremely challenging to define the sequence determinant of antibody specificity (see page 4). The specification does not provide a correlation between structure and function for the antibodies as broadly claimed. The specification discloses a single species of antibody having a VH of SEQ ID NO; 1 and a VL of SEQ ID NO: 5, and this is not sufficiently representative of the broad genus of antibodies encompassed by the present claims.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of antibodies and inhibitors encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning – i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Note the following Court Decisions regarding the written description of antibodies in the context of the current claims.
Given the claimed broadly class of antibodies, in the absence of sufficient disclosure of relevant identifying characteristics, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014) and the specification at best describes plan for making antibodies with the “limitations above” and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011). There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
No claim is allowed. Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim 1(so long as base claim 1 is also amended to overcome the objection to claim 1 noted above).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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