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 .
Applicant’s election without traverse of group I, claims 1, 79-88 and 92, in the reply filed on 8/27/26 is acknowledged. Applicant has further elected an Fc domain comprising S239D/I332E mutations as the species of functional domain and an antibody having SEQ ID NO: 67 and 68 as the species of antibody. Claims 89-91, 93-95 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1, 79-88 and 92 and are being acted upon.
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 81-83 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.
Claims 81-82 are indefinite in the recitation of specific Fc positions in the absence of a SEQ ID NO. or numbering scheme. The scope of the claims is indefinite since it is not clear how the residue numbers are to be identified. Amendment to recite that the mutations are according to EU numbering, for example, would be remedial.
Claim 83 recites CDR regions for VH and VL of SEQ ID NO: 67-68, respectively, which renders the claims indefinite. Different numbering schemes exist for CDR identification, and it is not clear what specific residues would be encompassed. The specification discloses certain exemplary CDR numbering schemes, but does not provide a limiting definition of CDR scope. For example, would numbering schemes that are not exemplified in the instant specification be encompassed by the present claims and if so which ones? The boundary of the claimed CDRs is unclear and indefinite
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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 1, 79-82 and 92 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 “binding molecules comprising a binding domain” that bind to PDGFRb.
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 genus of binding molecules comprising a binding domain that binds to PDGFRb. The claims broadly encompass any structure, i.e. a protein, a ligand, peptide, or even a small molecule, that function to bind to PDGFRb and also can enhance ADCC function when further comprising an Fc region. The state of the art is such that protein chemistry is one of the most unpredictable areas of biotechnology. Whisstock et al (Quarterly Review of Biophysics, 2003, 36, pp307-340) teach that the prediction of protein function from sequence and structure is a difficult problem, because homologous proteins often have different functions. Even single amino acid changes in a proteins amino acid sequence can have dramatic effects on protein function. For example, Wang et al., 2001, show that a single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipids growth factor receptors (e.g., abstract).
The specification does not disclose correlation between structure and function for the claimed binding domains. The only species of binding domains disclosed are antibody binding domains. This is not sufficiently representative of the broad genus of structures encompassed by any “binding molecule comprising a binding domain”.
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 binding domains 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). 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.
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) 1, 79, 86-87, and 92 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2013/085972 (of record).
WO 2013/085972 teaches antibodies that specifically bind to PDGRFb, wherein the antibodies have an Fc region, such as an IgG antibodies (see page 1, 7, and 28-29). WO 2013/085972 teaches that the Fc region can be an Fc variant comprising one or mutations that enhance ADCC, such as S239D and/or a mutation at position 332 (see page 29-31, in particular). WO 2013/085972 teaches humanized antibodies (see page 26, in particular). WO 2013/085972 teaches a therapeutic composition of the antibody and a pharmaceutically acceptable excipient (see page 39, in particular). Regarding binding to activated HSC, this is an inherent property of an antibody that binds PDGFRb.
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.
Claim 1, 79-82, 86-87, and 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013/085972 (of record), in view of WO2006085967.
The teachings of WO 2013/085972 are described above. WO 2013/085972 teaches that the Fc variant having enhanced effector function and FcR binding can be any art recognized Fc variant, and specifically discloses that the variants can be according to WO2006085967 (see page 30 in particular).
WO2006085967 teaches that S239D/I332E is a most promising Fc variant that enhances FcR binding and ADCC effector function (see paragraph 243 and 251, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to make use S239D/I332E Fc variant as taught by WO2006085967, as the Fc variant in the antibodies of WO 2013/085972. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO 2013/085972 explicitly suggest that the Fc variant having enhanced effector function and FcR binding can be according to WO2006085967.
Claims 1, 79-87 and 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 5,882,644, in view of WO 2013/085972 (of record) and WO2006085967.
The ‘644 patent teaches a humanized antibody that binds to PDGFRb comprising a VH of SEQ ID NO: 8 and a VL of SEQ ID NO: 6, which comprise identical VH and VL sequences as compared to SEQ ID NO: 67-68 of the instant application (See columns 22-28, in particular, see residues 20-137 of SEQ ID NO: 8 and residues 21-127 of SEQ ID NO: 6 and the attached alignments). The ‘644 patent teaches that the humanized antibodies comprising the VH and VL are joined to human constant sequences and teaches IgG1 antibodies (i.e. antibodies with two heavy and two light chains, see columns 19, 22-28, in particular). The ‘644 patent teaches a composition comprising a therapeutically effective amount of the antibody and a pharmaceutically acceptable excipient (See column 16, in particular). The ‘644 patent teaches the humanized antibodies with a human cK constant region and human gamma1 constant region (see columns 24-28, in particular).
The reference differs from the claimed invention in that it does not explicitly teach that the Fc region has S239D/I332E mutations.
WO 2013/085972 teaches antibodies that specifically bind to PDGRFb, wherein the antibodies can have a modified IgG Fc region that enhances Fc receptor binding and effector function, such as ADCC (see page 1, 7, and 28-30). WO 2013/085972 teaches that the Fc region can be an Fc variant comprising one or more mutations that enhance ADCC, such as S239D and/or a mutation at position 332 (see page 29-31, in particular). WO 2013/085972 teaches that the Fc variant having enhanced effector function and FcR binding can be any art recognized Fc variant, and specifically discloses that the variants can be according to WO2006085967 (see page 30 in particular). WO2006085967 teaches that S239D/I332E is a most promising Fc variant that enhances FcR binding and ADCC effector function (see paragraph 243 and 251, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the IgG1 Fc variant of WO 2013/085972 and WO2006085967, as the IgG1 Fc region in the antibodies of the ‘644 patent. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, in order to provide a modified PDGFRb antibody with enhanced Fc receptor binding and effector function, as taught by WO 2013/085972 and WO2006085967.
Claim 88 is rejected under 35 U.S.C. 103(a) as being unpatentable over 5,882,644, WO 2013/085972 and WO2006085967, applied to claims 1 above, and further in view of US 2014/0294812.
The combined teachings of 5,882,644, WO 2013/085972 and WO2006085967 are discussed above.
They do not explicitly teach SEQ ID NO: 106 and 107.
The ‘812 publication teaches IgG1 Fc variants of the IgG1 Fc sequence of SEQ ID NO: 2, wherein the variants can be S239D/I332E. The ‘812 publication teaches that S239D/I332E mutations exhibit improved FcgammaR binding and ADCC (see Fig. 1 and Fig. 22B, and paragraph 102, 311, in particular). The ‘812 publication teaches a kappa constant light chain sequence of SEQ ID No: 1. The ‘812 publication teaches that the Fc variants are useful in combination with any antibody antigen binding domain that targets virally any antigen, including transmembrane receptors for growth factors (see paragraph 138, in particular).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of the ‘812 publication, to the Fc variant PDGFRb antibodies made obvious by 5,882,644, WO 2013/085972 and WO2006085967. The ordinary artisan would be motivated to use the IgG1 Fc of SEQ ID NO:2 of the ‘812 publication, with the S239D/I332E mutations, since both the ‘812 publication and WO2006085967 teach that the mutations exhibits enhanced FcR binding and ADCC effector function. Doing so renders obvious SEQ ID NO: 106 of the instant application. See attached alignment which represents the VH of the PDGFRb antibody shown in resides 20-137 of SEQ ID NO :8 of the ‘644 patent, with the wild type IgG1Fc of SEQ ID NO: 2 of the ‘812 publication. The only difference between the two sequences is the S239D/I3332 mutations taught by both the ‘812 publication and WO2006085967. In other words, using the VH domain of the ‘644 patent, attached to an IgG1 heavy chain variant Fc region comprising S239D/I332E results in a sequence 100% identical to SEQ ID NO: 106 of the instant application. Regarding SEQ ID NO: 107, the ‘644 patent teaches that the humanized antibodies comprise a human cK constant region. As evidenced by the ‘812 publication, human ck constant region comprises SEQ ID NO: 1, which is identical to residues 108-214 of SEQ ID NO: 107 of the instant application. In other words, the antibody of the ‘644 publication would inherently have a light chain with the sequence of SEQ ID NO: 107. Alternatively, it would also be obvious to use the human Ck constant region sequence of the ‘812 publication in the variant IgG1 antibodies made obvious above, and doing so would result in a sequence identical to SEQ ID NO: 107 of the instant application (see attached alignment, which represents the PDGFRb VL of residues 21-127 of SEQ ID NO: 6 of the ‘644 patent, with the Ck constant region of SEQ ID NO: 1 of the ‘812 publication).
No claim is allowed.
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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