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 without traverse of group 1 with species as follows:
1) LRP5 binding domain to N-terminus and FZD4 binding domain to the C-terminus,
2) LRP5 binding domain comprising a diabody and FZD4 binding domain having two Fabs,
3) LRP5 CDR comprising
a. The VH of the first heavy chain monomer comprising CDR-H1, 2 and 3 of SEQ ID NOs: 528, 553, and 586 respectively,
b. The VL of the first heavy chain monomer comprising CDR-L1, 2 and 3 of SEQ ID NOs:1, 491, and 510 respectively,
c. VH of the second heavy chain monomer comprising CDR-H1, 2 and 3 of SEQ ID NOs: 536, 566, and 603 respectively,
d. VL of the second heavy chain monomer comprising CDR-L1, 2 and 3 of SEQ ID NOs: 1, 2 and 493 respectively.
FZD4 CDR comprising
a. The VH of the first heavy chain monomer comprising CDR-H1, 2 and 3 of SEQ ID NOs: 24, 61, and 90 respectively,
b. The VL of the first heavy chain monomer comprising CDR-L1, 2 and 3 of SEQ ID NOs:1, 2 and 12 respectively.
4) the first and second heavy chain monomer comprising SEQ ID NOs: 941 and 949 and the first and second light chain monomer comprising SEQ ID NO: 952.
in the reply filed on 9/18/2025 is acknowledged.
Claims 2-7, 10-11, 13-15, 17-19, 21-36, 38, 40-42, 44-51, 53, 55-62, 65, 67, and 71-77 have been cancelled.
Claims 78-96 have been added.
Claims 1, 8-9, 12, 16, 20, 37, 39, 43, 52, 54, 63-64, 66, 68-70 and 78-96 are pending.
Claims 43, 52, 54, 63-64, 66, 68-70, and 87-96 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 8-9, 12, 16, 20, 37, 39, and 78-86, drawn to a tetravalent binding antibody comprising bivalent LRP5 binding domain and bivalent FZD4 binding domain, are examined on merits.
Information Disclosure Statement
The information disclosure statement (s) (IDS) submitted on 6/22/2022, 7/31/2023, 1/22/2024, 6/13/2024, 8/16/2024, 1/07/2025, 1/16/2025, 1/18/2025, and 9/18/2025 are/is considered by the examiner and initialed copies/copy of the PTO-1449 are/is enclosed.
Interview Summary
Based on the sequence search result, allowable subject matter has been established in this application. For the compact persecution, applicant’s representative Jana E. Harris has been contacted on 10/21/2025 and again on 11/17/2025 for amending some of the claims including claim 1 in condition of allowance. Applicant is not ready to make amendment to the current claims and expect Office action to address the issues (also see interview summary).
Claim Rejections - 35 USC § 112
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.
Claims 1, 8-9, 12, 16, 20, 37, 39, and 78-86 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 pre-AIA the applicant regards as the invention.
The claims include two sets of claims based independent claim 1 and independent claim 78.
The claims are rejected because independent claim 1 recites a tetravalent binding antibody comprising bivalent diabody binding to LRP5 and bivalent Fabs to FZD4, which is considered to be represented by figure 6-7, diabody-Fc-Fab or ANT39 figure 15 as shown below, wherein the two Fabs binding to FZD4 comprise the same antigen binding domain with the identical CDRs.
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632
606
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Figure 6 Figure 7
The claims are also rejected because independent claim 78 recites the tetravalent binding antibody comprising first LRP5 binding domain and second LRP5 binding domain, which comprise two pairs of VH/VL domains binding to different epitope of LRP5 and a first FZD4 and second FZD4 binding domain and each comprising the same VH domain paired to the same VL domain with the same CDR sequences. Thus, the two FZD4 binding domain to the FZD4 with the same CDRs, is not considered as bivalent antibody.
The claims, as written, provide defined CDRs for VHs and VLs in first and second binding domains for LRP5, but recites the same set of 3 CDRs of a VH and 3CDRs of a VL for both binding domains to FZD4. Thus, it is not clear how and why the two same binding domains for FZD4 is considered as bivalent for FZD4 and in combination with two LRP5 binding domain considered as a tetravalent antibody. Clarification and/or correction would be appreciated.
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: Mixed-Matched VH and VL domains and VH switched in first and second LRP5 binding domain
Claims 78-84 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 example for the claimed method, by describing an actual reduction to practice of the claimed invention by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. 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, or any combination thereof.
Base claim 78 is drawn to a tetravalent binding molecule comprising:
(a) a first LRP5 binding domain comprising a VH comprising
CDR-H1 having the amino acid sequence of SEQ ID NO: 528,
CDR-H2 having the amino acid sequence of SEQ ID NO: 553, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 586; and
a light chain variable domain (VL) comprising
CDR-L1) having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 2, and
CDR-L3) having the amino acid sequence of SEQ ID NO: 493; and
(b) a second LRP5 binding domain comprising a VH comprising
CDR-H1 having the amino acid sequence of SEQ ID NO: 536,
CDR-H2 having the amino acid sequence of SEQ ID NO: 566, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 603; and
a VL comprising
CDR-L1 having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 491, and
CDR-L3 having the amino acid sequence of SEQ ID NO: 510; and
(c) a first Frizzled 4 (FZD4) binding domain and a second FZD4 binding domain, each comprising a VH comprising
CDR-H1 having the amino acid sequence of SEQ ID NO: 24,
CDR-H2 having the amino acid sequence of SEQ ID NO: 61, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 90; and
a VL comprising
CDR-L1 having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 2, and
CDR-L3 having the amino acid sequence of SEQ ID NO: 12.
wherein the first heavy chain monomer comprises the amino acid sequence of SEQ ID NO: 941 (697aa), the second heavy chain monomer comprises the amino acid sequence of SEQ ID NO: 949 (717aa), and the first light chain monomer and the second light chain monomer each comprise the amino acid sequence of SEQ ID NO: 952 (214aa, claim 84).
The specification (Pg publication, xxx8983) provides the following teaching for the structures of two heavy chains monomers comprising LRP5 diabody in the claimed tetravalent binding antibody
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The teaching of the specification is summarized as:
first LRP5 binding domain comprising
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 528, 553, and 586, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 49, and 510,
and second LRP5 binding domain comprising
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 536, 566, and 603, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 2, and 493.
Thus, as compared to antibody recited in claim 78, the specification teaches the first VH paired to the second VL and second VH paired to the first VL, which correspond to the sequence search results and shown in the result of sequence alignment, wherein the first LRP5 binding domain with VH-CDR1-3 (SEQ ID NOs: 528,553, and 586) paired to VL-CDR1-3 (SEQ ID NOs: 1, 49, and 510) is located within the first heavy chain monomer of SEQ ID NO: 941 and second LRP5 binding diabody with VH-CDR1-3 (SEQ ID NOs: 536, 566 and 603) paired to VL-CDR1-3 (SEQ IDNO: 1, 2 and 493) is located within the second heavy chain monomer of SEQ ID NO: 949 as below:
QY= fuse SEQ ID NO:528 to 553 to 586 (first VH set forth in the specification)
US-17-846-846-941
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 941, US/17846846
Publication No. US20230118983A1
GENERAL INFORMATION
APPLICANT: ANTLERA THERAPEUTICS, INC.
TITLE OF INVENTION: TETRAVALENT FZD AND WNT CO-RECEPTOR BINDING ANTIBODY MOLECULES
TITLE OF INVENTION: AND USES THEREOF
FILE REFERENCE: ANT-P3186USCIP
CURRENT APPLICATION NUMBER: US/17/846,846
CURRENT FILING DATE: 2022-06-22
PRIOR APPLICATION NUMBER: 63/127,408
PRIOR FILING DATE: 2020-12-18
NUMBER OF SEQ ID NOS: 1063
SEQ ID NO 941
LENGTH: 717
Query Match 75.1%; Score 76.6; Length 717;
Best Local Similarity 27.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 FSSSSI---------------SISSSYGYTY----------------------------- 16
|||||| ||||||||||
Db 29 FSSSSIHWVRQAPGKGLEWVASISSSYGYTYYADSVKGRFTISADTSKNTAYLQMNSLRA 88
Qy 17 ----------SWAM 20
||||
Db 89 EDTAVYYCARSWAM 102
QY= fuse SEQ ID NO: 1 to 49 to 510 (VL set forth in the specification):
US-17-846-846-941
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 941, US/17846846
Publication No. US20230118983A1
SEQ ID NO 941
LENGTH: 717
Query Match 71.5%; Score 62.9; Length 717;
Best Local Similarity 27.1%;
Matches 19; Conservative 0; Mismatches 0; Indels 51; Gaps 2;
Qy 1 SVSSA-----------------SASDLYS------------------------------- 12
||||| |||||||
Db 148 SVSSAVAWYQQKPGKAPKLLIYSASDLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYY 207
Qy 13 ---YAGAGLI 19
|||||||
Db 208 CQQYAGAGLI 217
QY= fuse SEQ ID NOs: 536 to 566 to 603 (second VH set forth in the specification):
US-17-846-846-949
Sequence 949, US/17846846
Publication No. US20230118983A1
APPLICANT: ANTLERA THERAPEUTICS, INC.
TITLE OF INVENTION: TETRAVALENT FZD AND WNT CO-RECEPTOR BINDING ANTIBODY MOLECULES
SEQ ID NO 949
LENGTH: 721
Query Match 79.2%; Score 96.6; Length 721;
Best Local Similarity 29.9%;
Matches 23; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 FTAYAM---------------SIYPSGGYTA----------------------------- 16
|||||| ||||||||||
Db 29 FTAYAMHWVRQAPGKGLEWVASIYPSGGYTAYADSVKGRFTISADTSKNTAYLQMNSLRA 88
Qy 17 ----------RSYYFAL 23
|||||||
Db 89 EDTAVYYCARRSYYFAL 105
QY= fuse SEQ ID NOs: 1 to 2 to 493 (second VL set forth in the specification):
US-17-846-846-949
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 949, US/17846846
Publication No. US20230118983A1
APPLICANT: ANTLERA THERAPEUTICS, INC.
TITLE OF INVENTION: TETRAVALENT FZD AND WNT CO-RECEPTOR BINDING ANTIBODY MOLECULES
Query Match 75.4%; Score 76.9; Length 721;
Best Local Similarity 28.2%;
Matches 20; Conservative 0; Mismatches 0; Indels 51; Gaps 2;
Qy 1 SVSSA-----------------SASSLYS------------------------------- 12
||||| |||||||
Db 151 SVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYY 210
Qy 13 ---YWAYYSPI 20
||||||||
Db 211 CQQYWAYYSPI 221
Note: the two diabodies binding to LRP5 having the CDRs of VH paired to the CDRs of VL described in the specification above are recited in the instant claim 1 that is not included in this rejection.
Accordingly, claim 78 having following recitation as
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 528, 553, and 586, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 2, and 493, and
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 536, 566, and 603, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 49, and 510
are considered as VH and VL switched or mixed and matched VH and VL domains. Those CDRs in VH and VL recited in claim 78 are not located within or correspond to the first heavy chain monomer having the sequence of SEQ ID NO: 941 and second heavy chain monomer having the sequence of SEQ ID NO: 949 as claimed in the dependent claim 84 (also see 112 4th rejection below).
Based on the teaching of the specification, the VH-VL switched or Mixed and Matched VH and VL domain are not considered to have the same LRP5 binding function and ability. The instant specification provides no proper description for the claimed antibody as there is no correlation between the structure of the antibodies and their claimed function, LRP5 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 own CDR switch could result in antibody having different affinity or even binding to totally different antigens as compared to the parent antibody. While the claims, as written, require alternations of entire 3 CDRs in VH paired to different VL or vice versa, it will be readily apparent to the ordinarily skilled artisan that novel VH/VL sequence pairs are created by substituting the first VH with structurally similar but different sequence of the second VH shown herein for the diabody as claimed. One skilled in the art would not know the switched or mixed and matched VH and VL can bind to epitopes of the antigen LRP5 as claimed without reducing to practice or quadrative experimentations.
As stated in the Written Description Guideline (2008), the levels of the skill and knowledge in the art would not be able to identify without further testing an antibody by VH-switched to match to a VL from another antibody that has the function as expected. Based on the lack of knowledge and predictability in the art those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of the antibodies.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common the genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties, “[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). Thus, 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.
The Court, in Abbvie v. Centocor (Fed. Cir. 2014), held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionallyclaimed genus.
The court has since clarified that this standard applies to compounds other than cDNAs. See University of Rochester v. G.D. Searle & Co., Inc., F.3d ,2004 WL 260813, at *9 (Fed.Cir.Feb. 13, 2004). Since the instant specification fails to provide sufficient descriptive information for VH and VL switched or mixed and matched antibody in the claimed tetravalent binding antibody to have a function for binding to two different epitopes, one of skill in the art would reasonably conclude that the inventor(s), at the time the application was filed, did not have possession of the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed, the skilled artisan cannot envision the claimed chemical structure(s) correlated with the claimed functional in the claimed antibodies binding to the epitopes or antigen. 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 reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Therefore, in view of the specification and knowledge of the art in the field. VH and VL switched or mixed and matched binding domain to LRP5 recited in the claimed tetravalent antibody does not meet the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is referred to written description guidance at http://www.uspto.gov/web/patents/guides.htm and recent memorandum (Feb 22, 2018): Clarification of written Description Guidance for Claims Drawn to Antibodies and Status of 2008 Training Materials.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 84 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 84, depending on previous claims encompassing the sequence definition for the first LRP5 binding domain of claim 78-(a) and second LRP5 binding domain of claim 78-(b), further recites that first heavy chain binding domain comprises the sequence of SEQ ID NO: 941 and second heavy chain binding domain comprises the sequence of SEQ ID NO:949. Claim 78 recites
(a) a LRP5 binding domain comprising VH comprising
CDR-H1-3 having the amino acid sequence of SEQ ID NO: 528, 553, and 586,
paired to VL comprising
CDR-L-1-3 having the amino acid sequence of SEQ ID NO: 1, 2 and 493
(b) a second LRP5 binding domain comprising VH comprising
CDR-H1-3 having the amino acid sequence of SEQ ID NO: 536, 566, and 603,
paired to a VL comprising
CDR-L1-3 having the amino acid sequence of SEQ ID NO: 1, 491, and 510.
However, the sequence searches for fused CDRs of SEQ ID NOs: 528 to 553 to 586 paired to fused CDRs of SEQ ID NOs: 1 to 2 to 493 do not correspond to the first heavy chain domain sequence of SEQ ID NO: 941, and the same searches for the fused CDRs of SEQ ID NOs: 536, 566, and 603 paired to fused CDRs of SEQ ID NOs: 1 to 491 to 510 do not correspond to the second heavy chain sequence of SEQ ID NO: 949 recited in claim 84. (see written description and sequence alignment above). Thus, the sequences of SEQ ID NO: 941 and 949 recited in claim 84 do not encompass the VH paired VL in the first and second LRP5 binding domain recited in the claim 78, therefore the claim does not further limit the previous claims.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13 (MPEP 9th Ed, Feb 2023).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Over Application:
Claims 1, 8-9, 12, 16, 20, 37, 39, and 78-86 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 5, 7-12, 15-18, 20-23, 25, 26, and 28 of copending Application No. 18/267914 (filed 12/17/2021). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims are directed to a tetravalent binding antibody comprising bivalent LRP5 binding domain, a bivalent FZD binding domain.
The both applications are from the same family and have the same filing date.
The instant claims are drawn to
a tetravalent binding antibody molecule comprising
(a) a Fc domain comprising CH3,
(b) a bivalent low-density lipoprotein receptor-related protein 5 (LRP5) binding domain, and
(c)a bivalent Frizzled 4 (FZD4) binding domain,
wherein the LRP5 binding domain comprising first low-density lipoprotein receptor-related protein 5 (LRP5) VH binding domain comprising
CDR-H1 having the amino acid sequence of SEQ ID NO: 528,
CDR-H2 having the amino acid sequence of SEQ ID NO: 553, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 586; and
a VL domain comprising
CDR-L1) having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 2, and
CDR-L3) having the amino acid sequence of SEQ ID NO: 493; and
a second LRP5 binding domain comprising a first VH comprising a
CDR-H1 having the amino acid sequence of SEQ ID NO: 536,
CDR-H2 having the amino acid sequence of SEQ ID NO: 566, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 603; and
a VL comprising
CDR-L1 having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 491, and
CDR-L3 having the amino acid sequence of SEQ ID NO: 510; and
a first Frizzled 4 (FZD4) binding domain and a second FZD4 binding domain, each comprising a VH comprising
CDR-H1 having the amino acid sequence of SEQ ID NO: 24,
CDR-H2 having the amino acid sequence of SEQ ID NO: 61, and
CDR-H3 having the amino acid sequence of SEQ ID NO: 90; and
a VL comprising
CDR-L1 having the amino acid sequence of SEQ ID NO: 1,
CDR-L2 having the amino acid sequence of SEQ ID NO: 2, and
CDR-L3 having the amino acid sequence of SEQ ID NO: 12.
The claims of application ‘914 are drawn to
a tetravalent binding antibody molecule comprising
(a) a Fc domain comprising CH3,
(b) a bivalent low-density lipoprotein receptor-related protein 5 (LRP5) binding domain, and
(c) a bivalent Frizzled 4 (FZD4) binding domain, wherein the LRP5 binding domain is diabody to LRP5 comprising CDR-H1-3 and CDR-L1-3 in table 3, 4, or 6 (claim 9)…
A method for promoting endothelial cell barrier function in a tissue comprising administering the tetravalent antibody of claim 1.
The tables in the 914 application provide the same CDR sequences for LRP5 (table 3: antibody ID 8716 and 12600) and CDR sequences for FZD4 (table 6: ANT39-Hole) as instantly claimed antibody.
Thus, both sets of the claims encompass the same tetravalent antibodis with the same antigen binding domain including same CDR sequences, the only difference is the claims of ‘914 application encompass more species of tetravalent antibodies as compared to the instantly claimed one or two tetravalent antibodies binding to LRP5 and FZD4. Thus. the species of the antibody with the same antigen binding domain recited in ‘915 application would anticipate and be obvious over the presently claimed antibody.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is allowed.
The bivalent LRP5 binding domains comprising
the first LRP5 binding domain comprising
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 528, 553, and 586, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 49, and 510, and
the second LRP5 binding domain comprising
a VH domain comprising VH-CDR1-3 of SEQ ID NOs: 536, 566, and 603, paired to
a VL domain comprising VL-CDR1-3 of SEQ ID NOs: 1, 2, and 493, are free of prior art.
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
The reference by Tao and inventors Angers, Sidhu, Blazer and Adams et al (eLife 2019, 8: e46134) teach tetravalent antibodies specifically binding to Frizzled family including FZD4 in Fab format, diabodies to LRP5/6 protein and Fc domain in between (figure 1 and page 10). Tao et al teach a method of selecting antibodies, but do not teach CDRs or VH and VL sequences for each of the antigen binding fragments in the tetravalent antibody as instantly claimed.
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.
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/LEI YAO/Primary Examiner, Art Unit 1642