DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims in the reply filed on 07/30/2026) is acknowledged. Claims 129, 130, 133, 135, 137, 142, 143, 240, 243, 260, 265, 266, 274 and 286 are pending and are examined.
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 129, 130, 133, 135, 137, 142, 143, 240, 243, 260, 265, 266, 274 and 286 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 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 inventors, at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). (emphasis added). See also MPEP 2163.04.
The claims are drawn to a method for eliciting an immune response or treating human hepatitis B virus (HBV) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a heterodimer comprising a human IgG4 Fc-IL-2v fusion protein comprising (i) a first amino acid sequence as set forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a first amino acid sequence set forth below; and (ii) a second Fc region comprising a second amino acid sequence set
forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a second amino acid sequence set forth below, respectively:
1) SEQ ID NO: 80 and SEQ ID NO: 46;
2) SEQ ID NO: 107 and SEQ ID NO: 46; or
3) SEQ ID NO: 114 and SEQ ID NO: 46.
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
In the instant Specification, Applicant disclose, in example 13, in vitro potency of 5 Fc-IL2variant fusion protein on cynomolgus macaque CD8+T cells and T reg cells (table 14); constructs 107.46, 108.46, 113.46, 114.46, 117.46 (where the first part represents the SEQ ID NO of the IL2v and the second part represents the SEQ ID NO: of the human IgG4 Fc). (Nota bene, the SEQ ID NO: 80 represents a IL2variant in which the position 281 may be X= R, S, G or A; the constructs 107, 108, 113, 114 and 117 comprise the position 281 that has R, R, G, G or R, respectively). The constructs 107.46 and 114.46, where further tested, in vitro, for activation of CD8+T cells from chronic HBV subjects (Example 20). Further, for the in vivo results, the specification disclose the use of the constructs 107.46 and 114.46, for pharmacodynamics of human Fc-IL-2 variant fusion proteins by monitoring numbers of peripheral blood CD8+T cells and Treg cells (example 19). In vivo results for actual antiviral and immune effects of murine surrogate Fc-IL-2 heterodimers in an HBV transgenic mouse model used two constructs: 167.250 or 165.250.
However, the claims are drawn to methods for eliciting an immune response or treating human hepatitis B virus (HBV) by using compounds that have at least 80% identity with three IL2variant constructs (SEQ ID NOs: 80, 107 and 114) fused with a human IgG4 Fc variant of SEQ ID NO: 46. The IL2v constructs have sequences consisting of 376 amino acid residues for an 80% identity that would entail 75 positions that could be altered (substitutions with possible other 19 natural amino acids, deletions or insertions); even for 99% identity that represents 3 positions to be altered. For SEQ ID NO: 46 (226 amino acids) for 80% identity that would comprise 45 positions that could be altered (substitutions with possible other 19 natural amino acids, deletions or insertions) or, for 99% identity, that represents 2 positions to be altered. Then the person of ordinary skill in the art would have to combine each IL2v construct with the possible variants of the Fc construct. The number of possible combinations would enormous (~ 105 -106), for this vast number of possible reagents, Applicant disclosed the actual use of only 2 constructs (107.46 and 112.46 and their corresponding murine surrogates). This would necessarily direct a skilled artisan that Applicant was not in possession of methods of use of compounds as broadly claimed but only for methods of use of the compounds having 100% identity with the constructs of SEQ ID NO: 80 and SEQ ID NO: 46; SEQ ID NO: 107 and SEQ ID NO: 46; or SEQ ID NO: 114 and SEQ ID NO: 46.
Claims 129, 130, 133, 135, 137, 142, 143, 240, 243, 260, 265, 266, 274 and 286 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 methods of use of the compounds having 100% identity with the constructs of SEQ ID NO: 80 and SEQ ID NO: 46; SEQ ID NO: 107 and SEQ ID NO: 46; or SEQ ID NO: 114 and SEQ ID NO: 46 does not reasonably provide enablement for using constructs having at least 80-99% identity with the above mentioned constructs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claims are drawn to a method for eliciting an immune response or treating human hepatitis B virus (HBV) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a heterodimer comprising a human IgG4 Fc-IL-2v fusion protein comprising (i) a first amino acid sequence as set forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a first amino acid sequence set forth below; and (ii) a second Fc region comprising a second amino acid sequence set
forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a second amino acid sequence set forth below, respectively:
1) SEQ ID NO: 80 and SEQ ID NO: 46;
2) SEQ ID NO: 107 and SEQ ID NO: 46; or
3) SEQ ID NO: 114 and SEQ ID NO: 46.
The specification disclosed, in example 13, in vitro potency of 5 Fc-IL2variant fusion protein on cynomolgus macaque CD8+T cells and T reg cells (table 14); constructs 107.46, 108.46, 113.46, 114.46, 117.46 (where the first part represents the SEQ ID NO of the IL2v and the second part represents the SEQ ID NO: of the human IgG4 Fc). (Nota bene, the SEQ ID NO: 80 represents a IL2variant in which the position 281 may be X= R, S, G or A; the constructs 107, 108, 113, 114 and 117 comprise the position 281 that has R, R, G, G or R, respectively). The constructs 107.46 and 114.46, where further tested, in vitro, for activation of CD8+T cells from chronic HBV subjects (Example 20). Further, for the in vivo results, the specification disclose the use of the constructs 107.46 and 114.46, for pharmacodynamics of human Fc-IL-2 variant fusion proteins by monitoring numbers of peripheral blood CD8+T cells and Treg cells (example 19). In vivo results for actual antiviral and immune effects of murine surrogate Fc-IL-2 heterodimers in an HBV transgenic mouse model used two constructs: 167.250 or 165.250.
The IL2v constructs have sequences consisting of 376 amino acid residues; for an 80% identity that would entail 75 positions that could be altered (substitutions with possible other 19 natural amino acids, deletions or insertions); even for 99% identity that represents 3 positions to be altered. For SEQ ID NO: 46 (226 amino acids) for 80% identity that would comprise 45 positions that could be altered (substitutions with possible other 19 natural amino acids, deletions or insertions) or, for 99% identity, that represents 2 positions to be altered. Then the person of ordinary skill in the art would have to combine each IL2v construct with the possible variants of the Fc construct. The number of possible combinations would enormous (~ 105 -106), for this vast number of possible reagents, and further the person of ordinary skill in the art would have to test each of the compounds for treating HBV or eliciting an immune response against HBV. Due to the immensity of the number of possible compounds this would represent an enormous amount of experimentation and thus represent un undue burden. For this reasons, the claims are considered enabled or the use of compounds having 100% identity with the sequences claimed.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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