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 of claims 23-39 in the reply filed on 06/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 23-44 are pending; claims 40-44 are withdrawn from prosecution. Claims 23-39 are currently examined.
Priority
This application claims priority to the provisional Applications 62/814,210,
62/814,744, 62/826,523. However, the SD binding protein against TROP2 is not
mentioned in any of the provisional Applications and thus effective file date of the
Application is 03/05/2020.
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 23-39 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 claim(s) 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 inventor(s), 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.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF- α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a
representative number of species falling within the scope of the genus or structural
features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the
state of the art at the time of the invention. For antibodies, the Federal Circuit has found
that possession of a mouse antibody heavy and light chain variable regions provides a
structural "stepping stone" to the corresponding chimeric antibody, but not to human
antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid
sequence information (a molecular description of the antibody) for a single mouse
variable region, i.e., the variable region that the mouse A2 antibody and the chimeric
antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the
claims.”). A chimeric antibody shares the full heavy and light chain variable regions with
the corresponding mouse antibody; that is, the structure shared between a mouse and
chimeric antibody would generally be expected to conserve the antigen binding activity.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from
its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a
fully-human antibody could be made does not suffice to show that the inventors of the
'775 patent possessed such an antibody.”)
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 case, the specification discloses the following fusion proteins (SEQ
ID NOs: 297-303 constructs comprising, from N- to C-terminal:
a) a first single domain antigen binding domain (sdABD) that binds to a human
TROP2 Atrop2 (SEQ ID NOs: 77, 81, 85, 89, 93 and 97), a first domain linker
(GGGSGGGS), a constrained anti-CD3 (2B2) Fv domain (comprising:
i) a first variable heavy domain comprising a vhCDR1, vhCDR2 and vhCDR3;
ii) a constrained noncleavable linker (CNCL); and
iii) a first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3), a second domain linker ((GGGSGGGS), a second domain antigen binding
domain (sdABD) that binds to a human TROP2 Atrop2 (identical with the first one), a MMP9 cleavable linker (SGGPGPAGMKGLPGS), a constrained anti-CD3 (2B2) pseudo Fv domain (comprising:
i) a first pseudo variable light domain comprising vlCDR1, vlCDR2 and vlCDR3,
ii) a non-cleavable linker (NCL); and iii) a first pseudo variable heavy domain comprising a vhCDR1, vhCDR2 and vhCDR3heavy variable domain), a third domain linker (GGGSGGGS) and a third sdABD that binds to human serum albumin (10GE) and a His 6 tag (grand total of 6 constructs).
However, the claims broadly encompass any fusion protein that comprises
a) a first single domain antigen binding domain (sdABD) that binds to any human tumor target antigen (TTA) (sdABD-TTA);
b)a first domain linker comprising any type of linkers (cleavable, non-cleavable, rigid, flexible, of any length);
c) a constrained Fv domain of a CD3 antibody comprising:
i) a first variable heavy domain comprising a vhCDR1, vhCDR2 and vhCDR3;
ii) a constrained non-cleavable linker (CNCL, of any length); and
iii) a first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3;
d) a second domain linker comprising any type of linkers (cleavable, non-cleavable, rigid, flexible, of any length);
e) a second sdABD-TTA to any human tumor antigen;
f) a cleavable linker (CL) (cleavable by anything known in the art);
g) a constrained pseudo Fv domain of a CD3 antibody (as long as having the same specificity as the first constrained Fv) comprising:
i) a first pseudo light variable domain;
ii) a non-cleavable linker (NCL, of any length); and
iii) a first pseudo heavy variable domain;
h) a third domain linker comprising any type of linkers (cleavable, non-cleavable, rigid, flexible, of any length); and
i) a third sdABD that binds to human serum albumin;
wherein said first variable heavy domain and said first variable light domain are capable
of binding human CD3 but said constrained Fv domain does not bind CD3; said first variable heavy domain and said first pseudo variable light domain intramolecularly associate to form an inactive Fv; said first variable light domain and said first pseudo variable heavy domain intramolecularly associate to form an inactive Fv; and wherein at least one of said sdABD-TTA binds human Trop2 and has a sequence selected
from SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89 and SEQ ID NO:93.
Due to the great variability of the type of the sdABD-TTAs, the indeterminate structure of the linkers, this genus is extremely vast and the specification disclosed only 6 constructs. In contrast to Applicant’s disclosure of the 6 specific constructs, the instant
disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus. A skilled artisan would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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