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 .
Status of the Claims
Claims 1 – 24 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
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 1 – 4, 6 – 7, 9 – 11, 13, 15 – 21, and 23 – 24 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 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure (MPEP) is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
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 BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1 – 4, 6 – 7, 9 – 11, 13, 15 – 21, and 23 – 24 are rejected as lacking adequate descriptive support for a possession of “an isolated antibody, comprising: complementarity determining regions (CDRs) capable of specifically binding to HSP90α epitope containing amino acid sequence EDK in amino acid 235 to 244 and amino acid 251 to 260 regions”, which encompasses a large number of antibody structures. However, the specification presents only Clone 2 and Clone 6 mouse anti-HSP90a antibodies in the Examples (specification under “Results”, p. 25) and several humanized versions of Clone 2 (specification at p. 25 – 27). Other examples of antibodies capable of specifically biding to the recited HSP90α epitope are not provided.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). See MPEP 2164.01.
Presently, the claimed antibody is only defined by functional properties: its ability to bind to HSP90a epitope containing amino acid sequence EDK in amino acid 235 to 244 and amino acid 251 to 260 regions. In view of the fact patterns detailed in Amgen v. Sanofi, the Applicant is not in possession of any antibody which can bind to the HSP90a epitope as presented by the claims.
The methods of claims 21 – 24 also have the same issue as that of the composition claims. Applicant has not described a reasonable number of agents capable of treating cancer desmoplasia in a subject.
Rather, Applicant has presented the public with an idea of how to perform an assay that might identify some agents that fall within the scope of the claims. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face. Because the agent administered in all of the pending claims reads on fragments, derivatives and analogs thereof, the agent does not have any particular conserved structure. Moreover, the specification does not disclose a structure/function correlation. Agents claimed with no structures that are only defined by function are generally not considered described.
Providing SEQ ID NOs that represent specific sequences for each CDR, VH, and VL, with each position of the sequence defined with a specific amino acid, can provide sufficient structures for the antibody or therapeutic agent of claims 1 – 4, 6 – 7, 9 – 11, 13, 15 – 21, and 23 – 24.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
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 and 6 – 7 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 1 – 3 and 6 each recite CDRs without defining the sequence of each CDR. For example, claim 2 recites “isolated antibody comprises: heavy chain complementary determining regions CDR1, CDR2 and CDR3 of a heavy chain variable region sequence of SEQ ID NO: 2 or SEQ ID NO: 12”; however, the claims do not disclose the sequence of each CDR. Each claimed amino acid sequence having four or more amino acids requires a sequence identifier. See MPEP 2412.
In addition, claims 1 – 3 and 6 do not indicate the numbering system used to delineate the CDRs. Although the specification states that “[t]he complementarity determining regions (CDRs) were identified by the published method. See Kabat E A, Wu T T, Perry H M, Gottesman K S, Foeller C. Sequences of proteins of immunological interest. U.S. Department of Health and Human Services, NIH, Bethesda, MD, 1991.” (specification at p. 21, under “Antibody Humanization and Optimization”), this teaching is not considered a limiting definition for the numbering system encompassed by the claims. Thus, the CDRs encompassed by claims 1 – 3 and 6 could be according to Kabat, CDRs according to Chothia, or they could be numbered according to other CDR boundary definitions that may not strictly follow one of Kabat or Chothia, in which case, the CDRs would potentially encompass different amino acids as shown in the example below.
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The antibody numbering system or standardized frameworks used to label amino acid residues in the variable regions of antibodies should be expressly stated in claims reciting CDRs. Because it is unclear what numbering system is being used, it is unclear what amino acid residues are required by the CDRs of the claims.
Claims 4 and 7 depend from claims 3 and 6, respectively, and thus inherit the deficiencies of claims 3 and 6.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 24 is rejected under 35 U.S.C. 102(a)(1)as being anticipated by FAN (Fan CS, et al. Endothelial-mesenchymal transition harnesses HSP90α-secreting M2-macrophages to exacerbate pancreatic ductal adenocarcinoma. J Hematol Oncol. 2019 Dec 17;12(1):138; see PTO-892: Notice of References Cited).
Independent claim 24 is directed to method for treating cancer desmoplasia in a subject, comprising: administering a therapeutic agent targeting eHSP90α to the subject.
According to the present specification, eHSP90α is an extracellular HSP90α. The present specification does not specifically define “a subject”.
FAN is directed to the finding that endothelial-mesenchymal transition (EndoMT) cells can secrete HSP90α to harness HSP90α-overproducing M2-type macrophages to promote pancreatic ductal adenocarcinoma (PDAC) tumor growth and that such effect can be targeted and abolished by anti-HSP90α antibody. FAN teaches that EndoMT can provide a source of cancer-associated fibroblasts which contribute to desmoplasia of many malignancies including pancreatic ductal adenocarcinoma (PDAC) and that anti-HSP90α antibody showed a potent therapeutic efficacy against the EndoMT and M2-macrophages-involved PDAC tumor growth. See FAN at the abstract.
FAN teaches that for the evaluation of the tumor-suppressive efficacy of anti-HSP90α antibody, the mice inoculated with Panc 02 cells plus OPN-treated 3B-11 cells were further intravenously injected with control IgG or anti-HSP90α antibody (5 μg per g of body weight for each dosage) on day 4. The injections were performed 8 times at 3-day intervals. See FAN at p. 3, left column, under “Mouse model” – right column, first paragraph.
Because FAN’s secreted HSP90α is considered an eHSP90α and FAN’s mouse is considered a subject, FAN anticipates the method of present claim 24.
Allowable Subject Matter
Claims 5, 8, 12, 14, and 22 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims.
FAN teaches an anti-HSP90α antibody as discussed above. However, an isolated antibody comprising CDRs capable of specifically binding to HSP90α epitope, which has the sequences of claim 5, 8, 12, 14, or 22 (wherein the heavy chain CDR1 has the sequence of SEQ ID NO: 3, the heavy chain CDR2 has the sequence of SEQ ID NO: 4, the heavy chain CDR3 has the sequence of SEQ ID NO: 5, the light chain CDRI has the sequence of SEQ ID NO: 8, the light chain CDR2 has the sequence of SEQ ID NO: 9, and the light chain CDR3 has the sequence of SEQ ID NO: 10; or wherein the heavy chain CDR1 having the sequence of SEQ ID NO: 13, the heavy chain CDR2 having the sequence of SEQ ID NO: 14, the heavy chain CDR3 having the sequence of SEQ ID NO: 15, the light chain CDR1 having the sequence of SEQ ID NO: 18, the light chain CDR2 having the sequence of SEQ ID NO: 19, and the light chain CDR3 having the sequence of SEQ ID NO: 20) recited in present claims 5, 8, 12, 14, and 22 is free of the art.
Conclusion
Claims 1 – 4, 6 – 7, 9 – 11, 13, 15 – 21, and 23 – 24 are rejected, and claims 5, 8, 12, 14, and 22 are objected to.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
