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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed June 1, 2023 has been considered and the references therein are of record.
Claim Objections
Claim 1 is objected to because of the following informalities: uses acronyms without writing the term prior to using the acronym, reciting, “GVHD” and “GVL”; “graft-versus-host-disease (GVHD)” and “graft-versus-leukemia (GVL)” should be inserted. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 11-12 and 22 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.
The term “immediately” in claim 11 is a relative term which renders the claim indefinite. The term “immediately” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “immediately” is not defined and renders the time span in which the multiple doses of the anti-IL-2 antibody are to be administered after HCT as indefinite.
Claims 12 and 22 recite the relative phrase “administered each day” which renders the claims indefinite because it is unclear as to the length of time being specified. It is unclear as to when “each day” begins relative to the subject receiving HCT and for what period of time the antibody is to be administered “each day.” For example, claim 13 adequately specifies the time period over which the antibody is to be administered every other day, limiting the administration to “every other day for a week, for two weeks, for three weeks, or for a month after HCT.” Claims 12 and 22 requires similar specificity that is supported by the Specification.
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 1-7 and 9-16 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 claims contain 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claims 1 and 15 recite an anti-IL-2 antibody that is capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation, which encompasses a genus of agents. Claims 4-7 are dependent on claim 1 and limit the genus of anti-IL-2 antibody to a monoclonal antibody, a monoclonal recombinant antibody, a human monoclonal recombinant antibody, and a humanized monoclonal recombinant antibody, respectively, that are capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation, which each encompasses a more limited genus of agents. Claim 16 is dependent on claim 15 and limits the genus of anti-IL-2 antibody to a monoclonal antibody, a recombinant antibody, a human antibody, or a humanized antibody that is capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation, which encompasses a more limited genus of agents. Claims 2-3 and 9-14 are dependent from Claim 1, do not materially limit the genus of agents, and are therefore included in the rejection. These claims do not require that the genus of the claims possess any particular structure or other distinguishing feature that is characteristic of the genus as a whole. Therefore, the claims are drawn to genera of antibodies for which there is inadequate written description.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a)(i)(C).
In the instant case, the only identifying characteristic present in the claim is a recitation of requisite activity (------------------i.e. capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation). There is not even identification of any particular portion of a structure that must be conserved for said activity. Regarding the genus of the claims, the specification describes one species that fall within the genus claimed (Specification para [0042]). From the specification, it is clear that Applicant is in possession of the specific species of JES6-1A12 antibody, a rat monoclonal IgG2a, κ, that was created using hybridoma technology by immunizing rats with recombinant mouse IL-2 and obtained from Bio X Cell (Specification para [0055]). The claims, however are not limited to that species and the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genera of antibodies as a whole, or representative number of species within the genera, the specification does not provide adequate written description of the claimed genera.
Claims 1-7 and 9-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for JES6-1A12 antibody, does not reasonably provide enablement for the genera of monoclonal anti-IL-2 antibody, monoclonal recombinant anti-IL-2 antibody, human monoclonal recombinant anti-IL-2 antibody, and/or humanized monoclonal recombinant anti-IL-2 antibody that are capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
The case law applies to the instant claims which require multiple genera of anti-IL-2 antibodies, yet the inventors have disclosed no amino acid sequences for any of the claimed anti-IL-2 antibody genera and have only disclosed use of the rat monoclonal IgG2a, κ, anti-IL-2 JES6-1A12 antibody.
In Amgen, the Supreme Court has stated:
“An antibody' s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.' Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody' s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody' s structure and function. Ibid.”
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc., V. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that: "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all of the disclosure related to the process is within the skill of the art","[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling for the full scope of the claimed invention because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Given that structure is essential to function; and given the unpredictability within the art with respect to creating antibodies, a person having ordinary skill in the art would have to perform further experimentation in order to make the genera of monoclonal anti-IL-2 antibody, monoclonal recombinant anti-IL-2 antibody, human monoclonal recombinant anti-IL-2 antibody, and/or humanized monoclonal recombinant anti-IL-2 antibody that are capable of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation encompassed by the claims and use them in the method claimed, commensurate in scope with the breadth of the claims. Given the nature of the invention, a skilled artisan would have to make many anti-IL-2 antibodies , then use those in the method claimed of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation in order to demonstrate making and using with a reasonable expectation of success. This amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
Thus, claims 1-7, and 9-16 lack enablement.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 7-11, 13-17, 21, and 23 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Zeng et al., 2018 (WO2018156955) (see IDS).
The instant claims are drawn to a method of preventing or treating acute graft-versus-host-disease (GVHD) while preserving graft-verse-leukemia (GVL) activity in a subject receiving an allogenic hematopoietic cell transplantation (allo-HCT) by administering an anti-IL2 antibody, such as the anti-IL-2-JES6 antibody, across various timepoints.
Zeng teaches a method of preventing or treating acute GVHD (para [0011]) while preserving GVL activity in a subject receiving an allogenic (para [0057]) hematopoietic cell transplantation (HCT) comprising administering to the human subject (para [0057]) a composition of an effective amount (para [0061]-[0062]) of an anti-IL-2 antibody, such as anti-IL-2-JES6 antibody (para [0097]), to the subject simultaneously with HCT, immediately before HCT, or immediately after HCT (para [0011]), wherein the antibody is monoclonal and/or humanized (para (0068]), the antibody is administered in multiple doses immediately after HCT (para [0065]), the antibody is administered every other day for up to 30 day after HCT (para [0071]) as required in instant claims 1-4, 7-11, 13-17, 21, and 23.
Therefore, Zeng anticipates instant claims 1-4, 7-11, 13-17, 21, and 23.
Claim Rejections - 35 USC § 103
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 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al., 2018 (WO2018156955) as applied to claims 1-4, 7-11, 13-17, 21, 23 above and in further view of Fleury et al., 2010 (CN201080007046) (see instant PTO-892).
Instant claims 5-6 are drawn to a method of preventing or treating acute graft-versus-host-disease (GVHD) while preserving graft-verse-leukemia (GVL) activity in a subject receiving an allogenic hematopoietic cell transplantation (allo-HCT), where the anti-IL-2 antibody is a recombinant and/or human antibody.
Zeng teaches a method of preventing or treating acute GVHD in a subject receiving allo-HCT by administering an anti-IL-2 antibody, where the antibody can be monoclonal and/or humanized (see above).
Zeng does not explicitly teach the anti-IL-2 antibody being a recombinant and/or human antibody as required in instant claims 5-6.
Fleury teaches the anti-IL-2 antibody can be a recombinant and/or human antibody (para [0205-0206]).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Zeng and Fleury. Monoclonal antibodies and recombinant antibodies are obtained through two different methods of production. Human antibodies and humanized antibodies are obtained from two different origins. One with ordinary skill in the art would be motivated to make and use the claimed invention because one would be motivated to obtain the most effective anti-IL-2 antibody, regardless of its method of production or origin. Furthermore, an ordinary artisan would be motivated to try antibodies produced through different methods and obtained from different origins to optimize the efficacy of the anti-IL-2-antibody. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Therefore, claims 5-6 are obvious in view of the disclosures of Zeng and Fleury.
Claims 12 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al., 2018 (WO2018156955) as applied to claims 1-4, 7-11, 13-17, 21, and 23 above and in further view of Pinana et al., 2006 (see instant PTO-892).
Instant claims 12 and 22 are drawn to a method of preventing or treating acute graft-versus-host-disease (GVHD) while preserving graft-verse-leukemia (GVL) activity in a subject receiving an allogenic hematopoietic cell transplantation (allo-HCT), where a single dose of the anti-IL-2 antibody, such as the anti-IL-2- JES6 antibody, is administered each day.
In the interest of compact prosecution, instant claims 12 and 22 are interpreted to mean every day for three days after HCT. This interpretation is based on the broadest reasonable interpretation of the statement, “In certain embodiments, the anti-IL-2 antibody is administered to the subject on the same day of receiving HCT, within 1 day of receiving HCT, within 2 days of receiving HCT, and within 3 days of receiving HCT,” found in paragraph 0042 of the specification.
Zeng teaches a method of preventing or treating acute GVHD in a subject receiving allo-HCT by administering an anti-IL-2 antibody, such as the anti-IL-2- JES6 antibody, every other day for up to 30 days after HCT (see above).
Zeng does not explicitly teach a single dose of the anti-IL-2- JES6 antibody administered each day for up to 3 days after HCT as required in claims 12 and 22.
Pinana teaches a method of preventing or treating acute GVHD in a subject receiving HCT by administering Inlimomab, an anti-interleukin-2 receptor (anti-IL-2R) monoclonal antibody, daily for 10 consecutive days after the subject has received HCT (abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosures of Zeng and Pinana. Since inlimomab and the claimed anti-IL-2 antibody both modulate IL-2 binding to IL-2R yet use slightly different dosing regimens, one with ordinary skill in the art would be motivated to make and use the claimed invention by combining the regime taught by Pinana with anti-IL-2 antibody taught by Zeng because one would want to find the optimal dosing regimen. In that pursuit, an ordinary artisan would be motivated, and find it obvious, to try administering the anti-IL-2 antibody every day instead of every other day to optimize the dosing regimen to make the most effective treatment. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Therefore, claims 12 and 22 are obvious in view of the disclosures of Zeng and Pinana.
Conclusion
No claims are allowed.
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/JOSEPH D. CESARE/
Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675