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
Claims 1-49 are pending in the instant application.
Claims 1-22 and 34-49 are withdrawn.
Claims 45-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/1/2026.
Claims 1-22 and 34-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/1/2026.
Restriction Response
Applicant’s election without traverse of Group I and Formula (III)
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, wherein:
M is -CH2-CH2-CH-;
W is an oxygen atom;
Lb is - NH-C(=O)-CH2-CH2-CH2-CH2-; and
T is -NH-OH,
in the reply filed on 6/1/2026 is acknowledged.
Priority
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C.
119(a)-(d) prior to declaration of an interference, a certified English translation of the
foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and
41.202(e).
Failure to provide a certified translation may result in no benefit being accorded
for the non-English application. The effective priority date is the filing date of
PCT/JP22/10574 filed on 3/10/2022 in the absence of a certified translation of
JP2021-039706 filed on 3/11/2021.
Claim Interpretation
Regarding instant claims 28-30 and 32-33, the instant specification defined the notation of: a) position 246/248 indicates that a lysine residue at position 246 or position 248 is a target; and b) position 288/290 indicates that a lysine residue at position 288 or position 290 is a target.
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.
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.
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 23-29 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/240287 (Yamada K et al. IDS reference) and evidenced by translated WO 2019/240287.
‘287 taught an azide group introduced antibody derivative in Example 84, wherein the structure is:
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(‘287 translated page 209, Table 5, [1597]), wherein the antibody is trastuzumab (Figs. 105-106) which is a humanized antibody containing a human IgG1 antibody, wherein selective conjugation was present on Lys246/Lys248 with EU numbering on the antibody heavy chains (‘287 translated page 203, [1545-1550]), wherein Table 5 identifies a ratio of 2 (shown above) and the ratio was taught as preferably 1-4 or 2 (‘287 translated page 58, [0238]). ‘287 taught a compound for conjugation comprised a linker following an affinity peptide, wherein the linker comprises a cleavable moiety, and wherein following the cleavable moiety the linker further comprises carbon chains of between 0 and 10 carbons before the reactive group R (‘287 translated page 6-12, [0012]). ‘287 taught successful conjugation of two conjugates to an antibody (translated ‘287 page 203, [1539]).
‘287 taught conjugation lysine residues present at predetermined positions in the CH2 domain can be efficiently modified at positions 246, 248, 288, and 290 (translated ‘287 page 32, [0030]).
‘287 taught conjugation to human antibodies such as laxivacumab (translated page 35, [0059]).
‘287 taught conjugation on Lys288 or Lys290 (translated 287 page 32, [0031]).
‘287 did not teach a single embodiment of Formula (III) wherein M is -CH2-CH2-CH-; W is an oxygen atom; Lb is - NH-C(=O)-CH2-CH2-CH2-CH2-; and T is -NH-OH, but this is obvious in view of the teachings of ‘287.
Regarding instant claims 23-29 and 31, it would have been obvious for a person having ordinary skill in the art to modify the azide group introduced antibody derivative in Example 84, wherein the structure is:, wherein the antibody is trastuzumab which is a humanized antibody containing a human IgG1 antibody, wherein selective conjugation was present
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on Lys246 or Lys248 with EU numbering on the antibody heavy chains – and:
Conjugate 2 azide group conjugates to the antibody for an r ratio of 2;
Extend the trivalent group of the linker by one or more carbons up to 10; and
Exchange trastuzumab for a human antibody such as laxivacumab.
This is obvious because:
‘287 Table 5 identifies a ratio of 2 in the drawing and ‘287 taught the ratio as preferably 2;
‘287 taught a compound for conjugation comprised a linker following an affinity peptide, wherein the linker comprises a cleavable moiety, and wherein following the cleavable moiety the linker further comprises carbon chains of between 0 and 10 carbons before the reactive group R. This would extend the trivalent group attached to the antibody by one or more carbons up to 10; and
‘287 taught conjugation to human antibodies such as laxivacumab.
There is a reasonable expectation of success because:
Table 5 identifies a ratio of 2 in the drawing and ‘287 taught successful conjugation of two conjugates to an antibody;
Extension of the trivalent group of the linker by one or more carbons up to 10 was considered by ‘287 to allow production of an antibody conjugate via displacement of the reactive group R and cleavage of the cleavable portion; and
The human antibody would also be expected to allow conjugation of the compound site specifically via its CH2 domain similar to trastuzumab.
This would produce an azide group introduced antibody derivative of
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, wherein Ig is trastuzumab or the human antibody laxivacumab (instant claims 25-26) which forms a regioselective amide bond on Lys246 or Lys248 (instant claim 28-29) with EU numbering on separate CH2 domains of the antibody heavy chains, wherein a trivalent group M is -CH2-CH2-CH- (instant claim 27), wherein W is an oxygen atom, wherein Lb is -NH-C(=O)-CH2-CH2-CH2-CH2-, wherein T is -NH-OH (instant claim 24), and wherein the average r is 2 (instant claim 31). This meets the claim limitations of the elected species in instant claims 23-29 and 31.
Claims 23-31 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/240287 (Yamada K et al. IDS reference) as applied to claims 23-29 and 31 above, and further in view of Yamada KL et al. (Angew. Chem., Int. Ed. 2019; 58: 5592 IDS reference) and WO 2019/240288 (Matsuda Y et al. IDS reference) and evidenced by translated WO 2019/240287 and translated WO 2019/240288.
‘287 is described above.
‘287 did not teach a single embodiment of Formula (III) wherein M is -CH2-CH2-CH-; W is an oxygen atom; Lb is - NH-C(=O)-CH2-CH2-CH2-CH2-; and T is -NH-OH, wherein the lysine conjugate is present at Lys 246/248 and Lys 288/290, but this is obvious in view of the teachings of ‘287, Yamada, and ‘288.
Yamada taught effective site-specific conjugation to trastuzumab K288 or K290 with conjugates comprising the peptide FNMQCQRRFYEALHDPNLNEEQRNARIRSIKDDC (Figure 1). Yamada taught effective conjugation to K288 or K290 with a peptide to antibody ratio of 1 or 2.
‘288 taught effectively conjugating multiple azide comprising chemical moieties or non-azide comprising chemical moieties site-specifically to an antibody with separate affinity peptides (translated ‘288, page 103-104, Table 5-6; page 87, [0577-0581]).
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Regarding instant claims 30 and 32-33, it would have been obvious for a person having ordinary skill in the art to modify the azide group introduced antibody derivative above of
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, wherein Ig is trastuzumab or the human antibody laxivacumab which forms a regioselective amide bond on Lys246 or Lys248 with EU numbering on separate CH2 domains of the antibody heavy chains, wherein a trivalent group M is -CH2-CH2-CH-, wherein W is an oxygen atom, wherein Lb is -NH-C(=O)-CH2-CH2-CH2-CH2-, wherein T is -NH-OH, and wherein the average r is 2 – and:
Exchange the regioselective conjugation from Lys246 or Lys248 to Lys288 or Lys290 in view of ‘287, Yamada, and ‘288
Include regioselective conjugation at Lys246 or Lys248 and Lys288 or Lys290 in view of ‘287, Yamada, and ‘288.
This is obvious because:
1a) ‘287 taught conjugation on Lys288 or Lys290;
1b) Yamada taught effective site-specific conjugation to trastuzumab K288 or K290;
2a) ‘288 taught effectively conjugating multiple azide comprising chemical moieties or non-azide comprising chemical moieties site-specifically to an antibody with separate affinity peptides;
2b) Yamada taught effective site-specific conjugation to trastuzumab K288 or K290, wherein the affinity peptide for regioselective conjugation is the same as ‘288; and
2c) ‘287 taught conjugation at Lys246 or Lys 248 and Lys288 or Lys290 and r as 1-4. Thus, regioselective conjugation to an antibody at Lys 246 or Lys 248 followed by conjugation to Lys 288 or Lys 290 would yield an azide group introduced antibody derivative with an r of 3-4 with regioselective conjugation to Lys 246 or Lys 248 and Lys 288 or Lys 290.
There is a reasonable expectation of success because:
1a) ‘287 taught conjugation on Lys288 or Lys290;
1b) Yamada taught effective site-specific conjugation to trastuzumab K288 or K290;
2a) ‘288 taught effectively conjugating multiple azide comprising chemical moieties or non-azide comprising chemical moieties site-specifically to an antibody with separate affinity peptides; Thus, multiple regioselective conjugations in the same construct are known.
2b) Yamada taught effective site-specific conjugation to trastuzumab K288 or K290, wherein the affinity peptide for regioselective conjugation is the same as ‘288; and
2c) ‘287 taught conjugation at Lys246 or Lys 248 and Lys288 or Lys290 and r as 1-4. Thus, regioselective conjugation to an antibody at Lys 246 or Lys 248 followed by conjugation to Lys 288 or Lys 290 would yield an azide group introduced antibody derivative with an r of 3-4 with regioselective conjugation to Lys 246 or Lys 248 and Lys 288 or Lys 290.
This would produce an azide group introduced antibody derivative of
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, wherein Ig is trastuzumab or the human antibody laxivacumab which forms a regioselective amide bond on: a) Lys246 or Lys248 wherein the average r is 2; b) Lys288 or Lys290 wherein the average r is 1-2 (instant claim 30); or c) Lys246 or Lys248 and Lys288 or Lys290 wherein the average r is 3-4 (instant claim 32-33) with EU numbering on separate CH2 domains of the antibody heavy chains, wherein a trivalent group M is -CH2-CH2-CH-, wherein W is an oxygen atom, wherein Lb is -NH-C(=O)-CH2-CH2-CH2-CH2-, and wherein T is -NH-OH. This meets the claim limitations of the elected species in instant claims 30 and 32-33.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN J SKOKO III whose telephone number is (571)272-1107. The examiner can normally be reached M-F 8:30 - 5:00.
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/J.J.S./Examiner, Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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