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 .
2. Applicant’s amendment filed on 12/29/2023 is acknowledged.
3. Claims 1-9 and 11-19 are pending and under consideration.
4. Applicant’s IDS documents filed on 01/17/2024 and 09/09/2025 have been considered.
Specification
5. REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosure is located on page 30 where two different sequences are indicated to be SEQ ID NO:27.
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Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
6. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
7. Claims 1-3, 5-9 and 11-19 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.
A. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “complementary determining region (CDR)” in claims 1-3 is used by the claim to mean variable domain or a polypeptide segment comprising CDR1, CDR2 and CDR3 while the accepted meaning is “one of three segments of a variable region of an antibody called CDR1, CDR2 and CDR3 which binds to a specific antigen.” Each of CDR1, CDR2 and CDR 3 is a complementary determining region (CDR), but the term does not refer to a polypeptide segment comprising all three regions. The term is indefinite because the specification does not clearly redefine the term.
B. Claim 2 recites that “Group 7” comprises SEQ ID NOs 22, 27 and 33. However, the MY1530-5-54 antibody of SEQ ID NO:7 which appears to be what is referred to by “Group 7” does not comprise instant SEQ ID NO:27.
C. On page 30 in the specification it discloses two different CDR sequences for SEQ ID NO:27 in lines 15-16 and 19-22. So, every recitation of SEQ ID NO:27 is indefinite.
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Correction is required.
8. 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.
9. Claims 1-3, 5-9 and 11-19 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is in possession of: a TROP2 binding single domain antibody VHH selected from the group consisting of SEQ ID NOs 1-8; a TROP2 binding single domain antibody VHH having all three CDRs of the VHHs selected from the group consisting of SEQ ID NOs 1-8 as recited in claim 2 with the exception of SEQ ID NO:7 which comprises the CDRs of SEQ ID NOs 22, ‘GYYHSGGT’ and 33; immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof; methods of administration thereof; and methods of treating tumors with high expression of TROP2.
Applicant is not in possession of: a TROP2 binding single domain antibody VHH having less than all three CDRs of the VHHs selected from the group consisting of SEQ ID NOs 1-8 as recited in claim 2 with the exception of SEQ ID NO:7 which comprises the CDRs of SEQ ID NOs 22, ‘GYYHSGGT’ and 33; immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof; methods of administration thereof; and methods of treating tumors as recited in claims 13 and 17.
The skilled artisan cannot envision all the polypeptide possibilities recited in the instant claims.
The specification describes the TROP2 specific VHHs of SEQ ID NOs 1-8. However, the claims broadly encompass a genus of any anti-TROP2 single domain antibody VHH chain comprising any combination of the 3 CDRs recited in claim 1 which encompasses CDR combinations that are not present in the VHHs that were actually produced in the specification. The specification only describes these VHHs, immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof and methods of administration thereof.
Consequently, conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
As evidenced by the art of Goel et al. (PTO-892; Reference U), Khan et al. (PTO-892;
Reference V) and Poosarla et al. (PTO-892; Reference W), antibody specificity for a particular antigen does not correlate with any particular structure for the antibodies themselves. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is
unpredictable which antibodies comprising the recited VHH would bind to TROP2. The specification does not disclose a correlation between the structure of the antibodies themselves and the functions of binding to TROP2 such that a skilled artisan would have known what antibody structures possess the claimed functions.
U.S. Court of Appeals for the Federal Circuit decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing
its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the
"newly characterized antigen" test could not stand because it contradicted the quid pro quo of the
patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872
F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345
(Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly
characterized antigen alone should not be considered adequate written description of a claimed
antibody to that newly characterized antigen, even when preparation of such an antibody is
routine and conventional. Id.
The specification does not provide adequate written description of the claimed invention.
The legal standard for sufficiency of a patent's (or a specification's) written description is
whether that description "reasonably conveys to the artisan that the inventor had possession at
that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111
(Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the
applicant had possession at the time of invention of the claimed inventions.
The claims encompass antibodies by only partial structure. The claims encompass sequences containing amino acids not found in the VHH single domain antibodies that were actually produced in the examples in the specification which actually bind to TROP2.
It is expected that all of the heavy and light chain CDRs in their proper order and in the
context of framework sequences which maintain their required conformation, are required in
order to produce a protein having antigen-binding function and that proper association of heavy
and light chain variable regions is required in order to form functional antigen binding sites.
MacCallum, et al. (PTO-892; Reference X) analyzed many different antibodies for
interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a
number of residues outside the standard CDR definitions make antigen contacts (see page 733,
right column) and non- contacting residues within the CDRs coincide with residues as important
in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al.
(PTO-892; Page 2; Reference U) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page
3079, right column). Although abbreviated CDR residues were used in the constructs, some
residues in all 6 CDRs were used for the constructs (see page 3080, left column). Thus it is
unpredictable as to what amino acids can be changed in the original intact antibodies disclosed in
the specification wherein the antibodies would still function. Thus, the skilled artisan cannot
envision the detailed structure of the encompassed invention and therefore conception is not
achieved until reduction to practice has occurred, regardless of the complexity or simplicity of
the method of isolation.
Adequate written description requires more than a mere statement that it is part of the
invention and a reference to a potential method of isolating it. In the instant application, the
amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601
at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In
view of the aforementioned problems regarding description of the claimed invention, the
specification does not provide an adequate written description of the invention claimed herein.
See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398,
1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225
(Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different
vertebrates or mammals, but had only described a single species of cDNA which encoded rat
insulin. The court held that only the nucleic acids species described in the specification (i.e.
nucleic acids encoding rat insulin) met the description requirement and that the inventors were
not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other
vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is
"unable to envision the detailed constitution of a gene so as to distinguish it from other materials.
. .conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v.
Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed
to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC,
July 1997) wherein is stated: "The description requirement of the patent statute requires a
description of an invention, not an indication of a result that one might achieve if one made that
invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming
rejection because the specification does "little more than outlin[e] goals appellants hope the
claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, naming a type of material generally known to exist, in the absence of knowledge as
to what that material consists of, is not a description of that material. Thus, as we have
previously held, a cDNA is not defined or described by the mere name "cDNA," even if
accompanied by the name of the protein that it encodes, but requires a kind of specificity usually
achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See
Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the VHH to demonstrate possession.
10. Claims 1-3, 5-9 and 11-19 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 : a TROP2 binding single domain antibody VHH selected from the group consisting of SEQ ID NOs 1-8; a TROP2 binding single domain antibody VHH having all three CDRs of the VHHs selected from the group consisting of SEQ ID NOs 1-8 as recited in claim 2 with the exception of SEQ ID NO:7 which comprises the CDRs of SEQ ID NOs 22, ‘GYYHSGGT’ and 33; immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof; methods of administration thereof; and methods of treating tumors with high expression of TROP2, does not reasonably provide enablement for : a TROP2 binding single domain antibody VHH having less than all three CDRs of the VHHs selected from the group consisting of SEQ ID NOs 1-8 as recited in claim 2 with the exception of SEQ ID NO:7 which comprises the CDRs of SEQ ID NOs 22, ‘GYYHSGGT’ and 33; immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof; methods of administration thereof; and methods of treating tumors as recited in claims 13 and 17 as recited in claims 1-3, 5-9 and 11-19.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification has disclosed the TROP2 specific VHHs of SEQ ID NOs 1-8. However, the claims broadly encompass a genus of any anti-TROP2 single domain antibody VHH chain comprising any combination of the 3 CDRs recited in claim 1 which encompasses CDR combinations that are not present in the VHHs that were actually produced in the specification. The specification only discloses these VHHs, immunoconjugates thereof, compositions there, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof and methods of administration thereof.
The specification is not enabled for the genus of VHHs, immunoconjugates thereof, compositions thereof, nucleic acids encoding, expression vectors thereof, host cells thereof, methods of production thereof, in vitro methods thereof and methods of administration thereof as cited supra with respect to the written description rejection. One of ordinary skill in the art at the time of invention would have been required to perform undue experimentation to make and use the genus of VHH as disclosed for the recited therapeutic and diagnostic purposes.
In addition, the specification is not enabled for the recited methods of treatment of any tumor. The art of Shvartsur et al. (PTO-892; Page 2: Reference V) teaches that Trop2 is expressed in normal tissues and it is overexpressed by various human carcinomas including, breast, cervix, colorectal, esophagus (some types), lung (some types), nonHodgkin's lymphoma, chronic lymphocytic lymphoma (CLL), Raji Burkitt lymphoma, oral squamous cell, ovarian, pancreatic, prostate, stomach, thyroid, urinary bladder, and uterine. Trop2 is not upregulated in the majority of esophageal, head, neck, and lung tumors and is not expressed in anaplastic large cell lymphoma (ALCL). Trop2 is overexpressed in some breast cancers and downregulated in others. In kidney and prostate cancer mRNA expression is downregulated. In lung and non-small cell lung cancer (NSCLC) it is downregulated. As such, the specification is not enabled for the use of the disclosed VHH for the treatment of any tumor. The specification is only enabled for the use of the disclosed VHH of SEQ ID Nos 1-8 for the treatment of tumors with high expression of TROP2. (In particular, whole document).
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
11. Claim 4 appears to be in condition for allowance.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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August 5, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights