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 .
Claims Status
The Amendment filed on 20May2024 is acknowledged in which claim(s) 5-8, 20-24, 26-32, and 37-162 were canceled by Applicant.
Applicant’s election without traverse of the invention of Group I and the species of a chimeric protein or protein complex comprising (a) a modified IL2 agent, wherein the modified IL2 agent comprises a N88G substitution relative to wildtype SEQ ID NO: 1; and (b) one targeting moiety, wherein the targeting moiety is directed against an immune cell, in the reply filed on 20May2026 is acknowledged.
Claim(s) 14, 35-36 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 20May2026.
Claim(s) 1-4, 9-13, 15-19, 25, 33-34 is/are currently pending and presented for examination on the merits.
Claim Objections
Claim 12 is objected to because of the following informalities: missing a comma between “IL2Rγ” and “or a combination” in line 2. Appropriate correction is required.
Claim Interpretation
Claims 1 (and 2-4, 9, 11-19, 25, 33-34) recite(s) a “modified IL2 signaling agent, wherein the modified signaling agent has one or more mutations or modifications relative to a wild type signaling agent having SEQ ID NO: 1…” in claim 1, line (a). The instant disclosure teaches that SEQ ID NO: 1 is the amino acid sequence for wild-type IL2 (IL2) [e.g., pg. 2, lines 10-12]. Therefore, the broadest reasonable interpretation of an “IL2 signaling agent” is a wild-type IL2, and as such, teachings of mutations and/or modifications to IL2 will be considered to apply for the limitation “modified IL2 signaling agent”.
Claims 10 recite(s) a “…exhibits reduced affinity for IL-2Rαβγ…” in line 2. The broadest reasonable interpretation of the phrase above is considered to include any prior art teachings of (1) reduced IL2R binding (because the recited IL2R heterodimer includes all known subunits: alpha, beta, gamma); and/or (2) reduced binding to individual IL2R subunits (e.g., IL2Ra, IL2Rb, IL2Ry).
Claims 12 recite(s) a “…exhibits ablated affinity for…” in line 2. The instant disclosure does not define “ablated”. Therefore, the broadest reasonable interpretation of “ablated” affinity is considered to mean any reduced affinity for the recited receptor(s).
Claims 16 recite(s) a “…targeting moieties are directed against a tumor cell…”. PD-1 is expressed on T cell lymphomas, as evidenced by Liu et al. (Cell Immunol. 2021 Aug; Epub 17Jun2021; e.g., abstract, introduction). Therefore, the broadest reasonable interpretation of the phrase above is considered to include an anti-PD-1 targeting moiety.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 1-4, 9-13, 15-19, 25, 33-34 is/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.
Claim(s) 1 (and 2-4, 9-13, 15-19, 25, 33-34) recite(s) “(b) one or more targeting moieties…or receptors of interest, wherein…one or more linkers, wherein the modified IL-2 signaling agent comprises…” in claim 1, lines 6-10. There is no joining word between “linkers” in line 9 and “wherein” in line 10 of claim 1, rendering the claim(s) indefinite. Specifically, it is unclear if the phrase means (1) only the limitations of lines 6-7, 8-9, or 10+ in are required, or (2) that all of the limitations recited in claim 1 (b) (e.g., claim 1, lines 6-10+) are required. For the purposes of compact prosecution, the phrase is considered to be joined by an “or” between “linkers” in line 9 and “wherein” in line 10. This rejection may be overcome by amending claim 1 (1) as recited above, or (2) to otherwise clearly claim the limitations of the instant invention. Claim(s) 2-4, 9-13, 15-19, 25, 33-34 can overcome this rejection by amending claim 1 as described above.
Claim(s) 19 recite(s) “…microprotein (e.g. cysteine knot protein, knottin)…” in line 4, rendering the claim indefinite. Specifically, the instant disclosure does not define the term “microprotein” and it is unclear if the phrase above means (1) the microprotein must be a knotted protein, (2) the microprotein does not require knots, and/or (3) if there is a specific size (e.g., residues, kDa, etc.) that the protein must be below to be considered a “microprotein”. For the purposes of compact prosecution, the phrase above is considered to be any protein comprising 150 amino acids or less. This rejection may be overcome by amending claim(s) 19 as recited above or to otherwise clearly claim the limitations of the instant invention.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 9-13, 15-19, 25, 33-34 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 2021/0094996 A1 (hereinafter “US996”).
Regarding instant claim(s) 1, 9-13, 19, US996 teaches a protein complex comprising a targeting domain (e.g., an scFv) and an IL2 mutein (e.g., modified IL2 agent) [e.g., ¶ ; fig. 19]. US996 teaches that IL2 mutein molecule(s) refer(s) to IL2 variants that have low affinity binding to IL2Rb and IL2Ry [e.g., ¶ 0151], and teaches an IL2 variant consisting of an N88G substitution (e.g., Q126L) [e.g., ¶ 0227].
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Regarding instant claim(s) 15, claims the composition (e.g., chimeric protein complex) of instant claim 1, wherein the one or more IL2 mutations “confers” reduced affinity or bioactivity that is restorable by attachment to one or more targeting moieties. There are no limitations recited in instant claim 15 that alter the composition of instant claim 1, therefore the additional limitations of instant claim 15 are considered to naturally flow from the composition as recited in instant claim 1. MPEP 2112.01(II) recites “Composition Claims- If the composition is physically the same, it must have the same properties…”.
Regarding instant claim(s) 16-18, 25, US996 further teaches the targeting domain is an anti-PD-1 domain that targets PD-1 on T cells (see claim interpretation above for claim 16) [e.g., ¶ 0018, 0095-0097].
Regarding instant claim(s) 33-34, US996 further teaches cells (e.g., host cells) comprising a vector comprising a nucleic acid encoding the chimeric protein complex (e.g., recombinant nucleic acid) [e.g., ¶ 0099, 0515].
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0094996 A1 (hereinafter “US996”), as applied to claim 1 above, and further in view of US 2005/0069521 A1 (hereinafter “US521”).
The teachings of US996 as recited above are applied.
Regarding instant claim(s) 2-3, US996 further teaches IL2 mutations include T3A [e.g., ¶ 225].
US996 does not expressly teach that the modified IL2 further comprises a T3A mutation.
Regarding claim(s) 2-3, US521 teaches IL2 comprising T3A exhibit extended half-lives, and that this overcomes the limitations of previous IL2 therapeutics short serum half-lives [e.g., title, abstract; ¶ 003-0006].
Further, it would have been obvious to a PHOSITA to modify the anti-PD-1/modified IL2 composition of US996 (see above) to include the that the modified IL2 further compromises a T3A mutation as taught by US521, because US996 teaches the base composition, and US521 teaches that T3A mutated IL2 have extended half-lives, thereby overcoming the previous limitations of IL2 therapeutics having a short half-life in serum (see above for details). There is an expectation of success for a PHOPSITA to further mutate the modified IL2 molecule of the anti-PD-1/modified IL2 composition of US996 to include that the modified IL2 further comprises a T3A substitution, because US996 teaches the base composition and IL2 substitutions comprising T3A (see above for details), and US521 teaches that T3A mutated IL2 have extended half-lives. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 2, 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0094996 A1 (hereinafter “US996”), as applied to claim 1 above, and further in view of US 11,896,648 B2 (Published 13Feb2024; Effective Filing Date 22Oct2020; hereinafter “US648”).
The teachings of US996 as recited above are applied.
US996 does not expressly teach that the modified IL2 further comprises a 5 residue N-terminal deletion.
Regarding claim(s) 2, 4, US648 teaches deletion of the first 5 residues results in active IL2 molecules that have increased serum half-life [e.g., abstract; col. 165, lines 21-26; tbl. A], and that the truncated IL2 variant is suitable for fusion proteins [e.g., col. 2, lines 44-51].
Further, it would have been obvious to a PHOSITA to modify the anti-PD-1/modified IL2 composition of US996 (see above) to include the that the modified IL2 further compromises a 5 residue N-terminal deletion as taught by US648, because US996 teaches the base composition, and US648 teaches that deleting the first 5 residues of IL2 results in extended half-lives (see above for details). There is an expectation of success for a PHOPSITA to truncate the first 5 residues from the N terminus of the modified IL2 molecule of the anti-PD-1/modified IL2 composition of US996, because US996 teaches the base composition, and US648 teaches that deleting the first 5 residues of IL2 resulted in extended half-lives and that such IL2 variants are suitable for use in fusion proteins (see above for details). This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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