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 and Previous Objections/Rejections Status
Claims 1-5,7 and 21-38 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Response to Arguments
Applicant’s arguments, see REMARKS, filed 11/7/25, with respect to the rejection(s) of claim(s) 1-5,7 and 21-38 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Robillard et al. (US 10,927,139B2) and also Robillard et al. (US 10,927,139B2) in view of Läppchen et al. (Nucl. Med. Biol. 55 (2017), 19-26) and in further view of Devaraj et al. (US2018/0244643A1).
New Grounds of Rejection
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.
Claim(s) 1,2,7 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Robillard et al. (US 10,927,139B2).
Robillard et al. (US 10,927,139B2) teaches of the tetrazine derivatives
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Molecular weight: 203.21 Molecular weight: 229.29 Molecular weight: 230.28 (column 56, lines 25-45; column 57).
The tetrazine derivatives anticipate the tetrazines of Formula (18) of the instant claims when n is 0; p is 0; y is 2,4 or 5; and R3 is OH,H or NH2.
The molecular weights of 203.21, 229.29 and 230.28 anticipate the molecular weights range of from 100 Da to 3000 Da of the instant claims.
With regards to the Log P values of the instant claim 2, products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable and does not render the old
composition patentably new to the discoverer. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
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.
Claim(s) 1-5,7 and 21-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Robillard et al. (US 10,927,139B2) in view of Läppchen et al. (Nucl. Med. Biol. 55 (2017), 19-26) and in further view of Devaraj et al. (US2018/0244643A1).
Robillard et al. (US 10,927,139B2) discloses tetrazine derivatives stated above.
The tetrazine derivatives further comprise the structure
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(column 46, lines 1-10) wherein R1 and R2 are selected from the groups consisting of alkyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2,6-pyrimidyl, 3,5-pyrimidyl, 2,4-pyrimidyl, etc. from a finite list of R1 and R2 substituents. The tetrazine
derivatives are more reactive towards dienophiles (column 47, lines 5-16). The alkyl is preferably lower alkyl (C-1-4 alkyl) (column 32, lines 13-15).
The tetrazines are an activator for the release of a substance linked to a trans-cyclooctene via an
inverse electron-demand Diels-Alder (IEDDA) reaction between the tetrazine and the trans-cyclooctene
followed by subsequent retro Diels-Alder reaction (rDA) (abstract; column 8, lines 12-23; column 30, lines 16-20; column 32, lines 18+).
Robillard et al. does not explicitly exemplify the pyridyl or pyrimidyl moieties of Formulas (12), (13), (15), (16) and (17).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the pyridyl moieties of the tetrazine derivatives
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with the 3-pyridyl, 4-pyridyl, 2,6-pyrimidyl, 3,5-pyrimidyl, 2,4-pyrimidyl, etc., with an expectation of success, to determine tetrazines that are most reactive towards the dienophiles for the release of a substance linked to a trans-cyclooctene as Robillard et al. states that the 2-pyridyl, 3-pyridyl, 4-pyridyl, 2,6-pyrimidyl, 3,5-pyrimidyl, 2,4-pyrimidyl, etc. substituted tetrazines are more reactive towards dienophiles.
Robillard et al. further discloses that tetrazine derivatives may be bound to a DOTA metal
chelator
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to further chelate 177Lu (columns 61 and 62; column 141, lines 58+).
The DOTA chelator encompasses the chelating moiety of the instant claims.
The 177Lu encompasses the metal ion, such as 177Lu of the instant claims.
Robillard et al. does not explicitly disclose binding the pyridyl-containing or pyrimidyl-containing tetrazine derivatives to a DOTA metal chelator.
Läppchen et al. (Nucl. Med. Biol. 55 (2017), 19-26) discloses tetrazine-DOTA compounds
comprising
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(Fig. 2). The DOTA chelating moiety chelates 177Lu for the method of pretargeted immuno-PET imaging and therapy via the biorthogonal inverse electron-demand Diels-Alder reaction between strained trans-cyclooctene and the tetrazine (abstract; p20, left column, first paragraph; p20, 2.2. Radiochemistry; Table 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to bind the pyridyl-containing or pyrimidyl-containing tetrazine derivatives, such
as
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,
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, etc. to a DOTA metal chelator to prepare a variety of radiolabeled tetrazines that are more reactive towards dienophiles for the method of pretargeted radioimmunoimaging and therapy.
Robillard et al. does not disclose the pyrazinyl moiety of the Formula (14).
Devaraj et al. (US2018/0244643A1) discloses tetrazine compounds
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wherein R2 comprises substituted or unsubstituted heteroaryl, etc.; L1 comprises substituted or
unsubstituted alkylene and R1 comprises a detectable moiety, such as gadolinium, etc. (p10, [0152-
0160]).
The substituted or unsubstituted heteroaryl moiety includes pyrazinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, etc. (p3-4, [0062]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the pyridyl moieties of the tetrazine compounds of Robillard et al.
with a pyrazinyl moiety as Devaraj et al. teaches that the pyrazinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl moieties are analogously substituted on tetrazine compounds and predictably yield tetrazine derivatives used for IEDDA and subsequent rDA reactions.
With regards to the instant claims 29-32, Robillard et al. further discloses the tetrazine
derivatives
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(column 58) that encompass the tetrazines of the instant claims when y is 1; n is 1; p is 1; R1 is N(R4)C(O); R4 is H; R2 is alkylene (C3); R1 is C(O) and R3 is OH.
With regards to the instant claim 33, Robillard et al. does not disclose binding the
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tetrazine derivative to a DOTA metal chelator.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to bind the tetrazine derivative
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to a DOTA metal chelator to prepare a radiolabeled tetrazine and examine the reactive of the radiolabeled tetrazine towards dienophiles for the method of pretargeted radioimmunoimaging and therapy as Robillard et al. and Läppchen et al. both teach of binding tetrazine derivatives to DOTA metal chelators via an amide bond of the linker moieties.
Conclusions
Claims 34-38 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618