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
Election/Restrictions
Applicant's election with traverse of group 1, drawn to a bispecific antibody to first and second antigens (elect CDH17 and CD3 in claim 2, SEQ ID NO: 21 in claim 6, and auristatin as cytotoxic agent in claim 15…) in the reply filed on 9/16/2025 is acknowledged. The traversal is on the ground(s) that there is no undue burden for searching both groups 1 and 2 because searching elected antibody should uncover a method treatment using the antibody. This is not found persuasive because in group 1, elected first antigen CDH17 (a liver-intestine cadherin) is not generally expressed in all cancers recited in group 2. Thus, the cancers listed in group 2 is not necessarily treated with the antibody of group 1. In addition, as set forth in the restriction requirement, the unity of two groups is lack in this application because the claimed antibody as the special technical feature linked groups 1 and 2 together does not make contribution over the prior art as set forth in the cited reference in the restriction requirement (page 4). For the reasons the requirement is still deemed proper and is therefore made FINAL.
Claims 4, 9-11, 17-25 and 28 have been cancelled.
Claims 31-36 have been added.
Claims 1-3, 5-8, 12-16, 26-27, 29-30 and 31-36 are currently pending.
Claims 1, 3, and 29-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Claims 2, 5-8, 12-16, 26-27, and 31-36, drawn to an antibody comprising scFv against 2nd antigen at C-terminus and Fab against first antigen, wherein the first and second antigens are CDH17 and CD3 (elected), and wherein the antibody comprises the sequence of SEQ ID NO: 21, are examined on merits.
Information Disclosure Statement
The information disclosure statement (s) (IDS) submitted on 11/13/2020 are/is considered by the examiner and initialed copies/copy of the PTO-1449 are/is enclosed.
Priority
The effective filing date for examined claims in this application is given to the filing date 5/16/2018 of the provisional US application 62/672325.
Claim Objection
1. Claims 6, 33 and 35-36 are objected to because the claims contain a clause an amino acid sequence of SEQ ID NO: …. The clause an amino acid sequence of SEQ ID NO: reads as a few amino acids within the sequences, which could be a portion of the sequence. The specification teaches the scFv or VH/VL or heavy or light chains of the claimed antibodies having entire sequences of the scFv or VH/VL domain that are not a portion of the sequences as disclosed in the specification.
Amending the clause “comprising an amino acid sequence of SEQ ID NO:…” to “comprising the amino acid sequence of SEQ ID NO:…” would overcome the objection.
2. Claim 2 is objected to because of improper Markush language used in the claim. The claim contains “Markush groups” as
….. wherein the first target and the second target are selected independently from a group comprising CDH17, CD3, TROP2, GPC3, and HER2.
This is improper Markush language. The claim should recite alternatives in a format such as “selected from the group consisting of A, B, and C” (see MPEP 2173.05(h) and 803.02). Amending the claims to the right format of Markush type would be appreciated.
3. Claim 6 is objected to because it recites:
The antibody of claim 2, comprising an amino acid sequence having SEQ ID NO: 15-33.
Thus, it is not clear how many SEQ ID NOs: or fusion of the sequences of the SEQ ID NOs comprised in the bispecific antibody recited in claim 2. Amending the claim clearly states which SEQ ID NO(s) are included in the antibody of claim 2 would be preferred.
4. Claims 7-8 are objected to as typographic errors as reciting
….the antibody of claim 2, wherein the scFv domain has specificity again antigen CD3 and CD17.
Base claim 2 encompasses first and second antigens of CDH17, CD3, TROP2…but no CD17. Correction is required.
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.
Written Description:
1) Mixed and Matched VH/VL domain;
2) bispecific antibodies without structure definition.
Claims 2, 5-8, 12-16, 26-27, and 31-36 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.
To satisfy the written description requirement, a patent 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. Possession may be shown. For claimed product the specification must provide sufficient distinguishing identifying characteristics of the genus, including disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, level of skill and knowledge in the art, and predictability in the art or any combination thereof.
An antibody having a N-terminal and a C-terminal, comprising,
a heavy chain comprising a scFv at the C terminus, and a light chain,
wherein the heavy chain and the light chain form a Fab domain having a specificity against a first target, wherein the scFv has a specificity against a second target, and
wherein the first target and the second target are selected independently from a group comprising CDH17, CD3, TROP2, GPC3, and HER2,
wherein Fab or scFv is CDH17 or CD3,
the antibody of claim 2, comprising an amino acid sequence having SEQ ID NO: 15-33,
wherein the heavy chain comprising an amino acid sequence selected from SEQ ID NO: 18,19, or 20 and light chain is SEQ ID NO: 21.
Applicant elects CDH17 and CD3 as first and second targets.
Thus, the claims comprise genus of bispecific antibodies with a structure comprising any Fab or any scFv located at either N- or C- terminal regions that targets CDH17 or CD3 (elected two targets).
Claim 6 recites antibody sequences comprising heavy and light chains without further define how the heavy and light chain pairs. Thus, the claim comprises Mixed and Matched VH/VL or heavy/light chains.
Claims 33 and 35 recite …..an amino acid sequence of (selected from) SEQ ID NO:… which read on a few amino acids or a portion of the sequence from the SEQ ID NO (also see objection above).
The specification teaches numbers of CDH17 X CD3 bispecific antibodies, wherein specifically teaches h10G1fL, h10G2fL and h10G4fL (CDH17 full antibody comprising Fab linked to scFv against CD3 at C-terminus) function as anti-CDH17 expressing tumor agent for treatment (examples 6-9), wherein the h10G1fL, h10G2fL, and h10G4fL have the sequences of heavy chain as SEQ ID NO: 18, 19 and 20 respectively paired to a common light chain SEQ ID NO: 21.
However, the specification provides:
1. no proper description for the claimed bispecific antibody with Mixed and Matched VH and VL as there is no correlation between the structure of the antibodies and their claimed function for CDH17 or CD3 binding. It is well known, the CDRs in VL and VH are the critical amino acids for the antigen recognition and affinity of binding, one amino acid change within the CDRs or one CDR switch could result in antibody having different affinity or even binding to totally different antigens as compared to the parental antibody.
2. the specification does not describe the bispecific antibody with a structure comprising anti-CDH17 scFv located at C-terminus and anti-CD3 Fab or whole antibody at N-terminus. As indicated in the reference by Kuo et al, a bispecific antibody comprising anti-CD3 scFv located at C-terminus could help prevent non-specific T-cell and achieve T cell- mediated target cell killing activities (abstract and figure 3). Thus, the claimed pharmaceutical composition comprising the bispecific antibody for anti-tumor function should have the Fab binding to the tumor antigen and scFv for CD3 binding domain for T-cell activity.
Thus, the specification defines the locations of Fab and scFv of the bispecific antibodies to tumor antigen and T cell activation, but does not provide description for the claimed antibodies with Fab and scFv at any location binding to any targets.
Therefore, only the humanized bispecific antibody to first target of CDH17 comprising a Fab of the heavy chain of h10G1fL, h10G2fL and h10G4fL having the sequence of SEQ ID NO:18, 19 or 20 at N-terminus paired to the light chain sequence of SEQ ID NO: 21 and scFv binding to CD3 as the second target, but not the bispecific antibody as claimed, meet the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claims 2, 5, 7-8, 12-16, 26-27, and 31-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuenkele et al (US 20180179287, filed Dec 21, 2017, priority to Dec 2016) in view of Kuo et al (Protein Eng Des & Sele, 25:561-569, 2012).
Kuenkele et al teach a bispecific or tetravalent antibody comprising one binding domain Fab to CDH17 located at N-terminus and another binding domain scFv (anti-TRAILR2) located at C-terminus (figure 1b and [0485-497, example 3]).
PNG
media_image1.png
414
384
media_image1.png
Greyscale
Kuenkele et al teach that CDH17 antibody recognizes the elevated antigen expressing cell, and teach the bispecific antibody attached to another cytotoxic drug or an anti-cancer agent (conjugate), [0113] and [0424]) and teach that the bispecific antibody is prepared in a pharmaceutical composition, which further comprises a cytotoxic agent, anti-cancer antibody or chemotherapeutic agent including cisplatin, irinotecan, checkpoint inhibitory antibodies, anti-EGFR or other anti-tumor growth factor antibodies…..for treating a cancer including gastric or liver cancer (abstract, [0074], [0113], [0426-450, and [0457-0468]).
Kuenkele et al do not teach the bispecific antibody comprising anti-CD3 scFv or anti-CD3 Fab located at either N- or C-terminus.
Kuo et al teach engineered bispecific antibody comprising anti-CD3 scFv located at C-terminus (abstract, figure 1-A Bif) and teach that C-terminus of anti-CD3 could help preventing non-specific T-cell activity and achieve T cell- mediated target cell killing ability (abstract and figure 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to combine the methods to form a bi-specific anti-CDH17 X anti-CD3 antibody with expected result. One of ordinary skill in the art before the effective filing date of was made would have been motivated to with reasonable expectation of success to combine the teaching of Kuo with the teachings of Kuenkele in order to benefit the treatment for CDH17 expressing cancer because Kuenkele et al have shown bispecific antibody comprising a cancer cell binding anti-CDH17 Fab and Kuo et al have shown bispecific antibody comprising anti-CD3 scFv in the C-terminus of the antibody and teach advantage of T cell activation by anti-CD3 scFv. One of ordinary skill in the art before the effective filing date of was made would have been also motivated to with reasonable expectation of success to form a bispecific antibody comprising anti-CD3 as Fab at N-terminus and anti-CDH17 scFv located at C-terminus to arrive at current invention (claim 32). Therefore, the references in combination teach every limitation of the claims and the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention was made, absent unexpected results.
Conclusion
No claim is allowed.
The anti-CDH17 antibody comprising the heavy chain sequence of SEQ ID NO: 18, 19 or 20 paired to the light chain sequence of SEQ ID NO: 21 is free of prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lei Yao, whose telephone number is (571) 272-3112. The examiner can normally be reached on 8:00am-6:00pm Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LEI YAO/Primary Examiner, Art Unit 1642