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
Claim Status
Applicant’s amendment filed May 18, 2023 was received and entered.
Claims 1-15 have been canceled.
Claims 16-35 have been added.
Claims 16-35 are pending and under consideration.
Priority
This application is a 371 of PCT/EP2021/082383 filed November 19, 2021, which claims priority to foreign application EP 20306424.1 filed November 20, 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on May 18, 2023 and July 28, 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 16-19, 25-26, 28-30, 32, and 34 are objected to for the following informalities:
Claim 16 (line 1) - delete extra word “antibody or antigen-binding fragment”.
Claim 16 (line 4) - should read “complementarity-determining regions (CDRs):”.
Claims 17-19 - the word “Or” that separates each embodiment of the anti-CD25 VL CDR amino acid sequences should not be capitalized.
Claim 25 - should read “the isolated anti-human CD25 antibody or antigen-binding fragment thereof according to claim 16, wherein said isolated antibody or antigen-binding fragment is
Claim 26 - should read “the isolated anti-human CD25 antibody or antigen-binding fragment thereof according to claim 16, wherein said isolated antibody or antigen-binding fragment is
Claim 28 (line 3) - to be consistent with the previous claims, the word “an” should be deleted from the phrase “anti-human CD25 antibody or antigen-binding fragment thereof”.
Claim 29 (line 2) - should read “a fusion protein”.
Claim 29 (line 3) - to be consistent with the previous claims, the word “an” should be deleted from the phrase “anti-human CD25 antibody or antigen-binding fragment thereof”.
Claim 30 (lines 3, 5, 8) - to be consistent with the previous claims, the word “an” should be deleted from the phrase “anti-human CD25 antibody or antigen-binding fragment thereof”.
Claim 30 (line 8) - a comma should be added after the phrase antigen-binding fragment thereof” to be consistent with the previous claims.
Claim 32 (line 9) - a comma should be added after the phrase antigen-binding fragment thereof” to be consistent with the previous claims.
Claim 34 (line 8) - a comma should be added after the phrase antigen-binding fragment thereof” to be consistent with the previous claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claim 22 is rejected under 35 U.S.C. 112(a), 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, at the time the application was filed, had possession of the claimed invention.
Claim 22 recites the isolated anti-human CD25 antibody can be a chimeric, humanized, or human, however the instant application does not explicitly disclose any human anti-human CD25 antibodies.
The instant specification discloses methods for generating a humanized antibody by immunizing transgenic animals that have been engineered to express a human antibody repertoire, or by selection of antibody repertoires using phage display methods [pg. 67, lines 17-23]. Although the use of transgenic animals and phage display libraries can be used to produce human antibodies, the instant specification provides no examples of how to generate fully human anti-CD25 antibodies as presently claimed.
Furthermore, the instant specification provides no details on how anti-CD25 antibodies of the present invention (H09, DO1, E04-2, B05, C01, GO1, G02-2, F03, D05, B07, B12) were generated. Therefore, there is no evidence that the disclosed antibodies are fully human antibodies against human CD25 as presently claimed.
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., 48 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 Vas-Cath, p. 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, p. 1116).
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.
As such, a person having ordinary skill in the art would not be able to envision a human anti-human CD25 antibody having human framework and human CDR regions when the instant claims recite only the VH and VL CDR regions.
Claims 30-31 are rejected under 35 U.S.C. 112(a), first paragraph, because the specification, while being enabling for:
A method of inducing specific lysis of CD25 positive cells without inhibiting IL-2 signaling in T-cells, comprising the step of administering to a subject a therapeutically effective amount of the isolated anti-human CD25 antibody or antigen-binding fragment thereof according to claim 16,
does not reasonably provide enablement for:
A method for treating a cancer or an infectious disease in a subject in need thereof, comprising administering to the subject the isolated anti-human CD25 antibody or an antigen-binding fragment thereof according to claim 16.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. With these teaching in mind, an enabling disclosure, commensurate in scope with the breadth of the claimed invention, is required.
The instant claims are directed to a method of treating a cancer or infectious disease comprising administering to a subject an isolated antibody that specifically binds human CD25. However, the disclosure only recites examples wherein the anti-CD25 antibodies of the present invention (H09, DO1, E04-2, B05, C01, GO1, G02-2, F03, D05, B07, B12) induced antibody dependent cell phagocytosis in a cell culture model and depleted Treg cells from anti-CD3+anti-CD28 activated human peripheral mononuclear cells in in vitro assays [pg. 144]. However, the instant claims broadly encompass treating any cancer or infectious disease with the instantly claimed anti-CD25 antibodies.
The state of the art regarding anti-CD25 antibodies for the use in treating cancer is a complex process. For example, as taught by Vargas et al. (2017; cited IDS 7/28/2023), CD25 is constitutively expressed on Treg cells, which are regarded as one of the major obstacles to the successful clinical application of tumor immunotherapy. Therefore, most cancer therapies target Treg cells by depletion or modulation. However, most anti-CD25 antibodies have displayed limited activity against established tumors [Introduction]. Further, although the frequency of circulating or tumor-infiltrating Tregs has been associated with poor patient survival in many cancers including breast, melanoma and lung, high infiltrates of Tregs have been associated with a positive outcome of patients in some cancers including colorectal, bladder and esophageal [Abstract] (Ward-Hartstonge and Kemp, 2017).
The state of the art regarding anti-CD25 antibodies for the use in treating infectious diseases is also complex and unpredictable, and can often lead to worse outcomes. For example, a study by Huo et al. (2016) teaches depletion of Tregs in mice with chronic peritonitis that were treated with anti-CD25 antibodies results in significantly increased bacterial clearance and survival. However, mortality significantly increases upon subsequent sub-acute sepsis. These results demonstrate that using anti-CD25 antibodies to deplete Tregs for the treatment of sepsis can ameliorate immunosuppression through increasing T cells and NK cells responses which is beneficial for preventing chronic infection, but will likely have deleterious effects during later stages of infection [Abstract].
Thus, given the unpredictability of the art and the breadth of the claims, the instant specification must provide a sufficient an enabling disclosure commensurate in scope with the instant claims. The specification provides guidance for using non-blocking anti-CD25 antibodies for Treg depletion and antibody dependent cell phagocytosis, which may be useful in the treatment of some cancers. The specification does not provide any guidance or examples for using non-blocking anti-CD25 antibodies for the treatment of any cancer or infectious disease as broadly encompassed by the instant claims. Thus, given the unpredictability of the art and the lack of guidance provided by the instant specification, it would require undue experimentation to practice the method as broadly claimed.
Claim 31 is included in the rejection as it depends from and requires all the limitations of the rejected claim.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
Claim 16 is drawn to an isolated anti-human CD25 antibody or antigen antigen-binding fragment thereof, wherein the variable region of the heavy chain (VH) comprises the three following complementary-determining regions (CDRs):
CDR1: NHAMA (SEQ ID NO: 1);
CDR2: VISYDGX1NX2YYX3DSVKG (SEQ ID NO: 2), wherein X1 is S or D, X2 is K or T, X3 is A or R; and
CDR3: GX4NSGYD (SEQ ID NO: 3), wherein X4 is W or L; and
wherein the variable region of the light chain (VL) comprises the three following CDRs:
CDR1: RASQX5X6X7XsX9LN (SEQ ID NO: 4), wherein X5 is S or N, X6 is V or I, X7 is N or S, X8 is S or K, X9 is F or Y; and
CDR2: GTX10SLQS (SEQ ID NO: 5), wherein X10 is S or N; and
CDR3: QQYX11SWPWT (SEQ ID NO: 6), wherein X11 is T or N.
The amino acid substitutions recited in claim 16 correspond to the VH and VL CDR amino acid sequences recited in claims 17-21. The amino acid sequences for all claimed anti-CD25 antibody CDR regions are free of prior art. The closest prior art to the claimed amino acid sequences, WO 2020/234399 (cited IDS 5/18/2023), is directed towards anti-CD25 antibodies, however, does not teach or suggest the amino acid sequences of the CDR regions of the presently claimed isolated anti-human CD25 antibodies.
Conclusion
Claims 20-21, 23-24, 27, 33, and 35 are allowed.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644