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
Status of the Claims
1. Claims 1-17 are the original claims filed on 9/30/2019. In the preliminary amendment of 8/10/2020, Claims 3, 7-12, and 14-16 are amended. In the response of 11/5/2021, Claim 17 is amended, Claims 1-16 are canceled and new Claims 18-36 added. In the response of 6/9/2022, Claims 17, 26-27 and 31-36 are amended, and Claim 30 is canceled. In the response of 12/27/2022, Claim 17, 31-36 are amended. In the response of 5/16/2023, Claim 17 is amended, Claims 31-34 and 36 are canceled and new Claim 37 is added. In the response of 9/28/2023, Claims 17-19 are amended, and Claims 28-29 are canceled. In the response of 11/28/2023, Claim 17 is amended. In the Response of 4/25/2024, Claim 17 is amended and Claims 23 and 26 are canceled. In the Response of 10/31/2024, no claims are amended, canceled or added. In the Response of 5/2/2025, claim 17 is amended and claim 20 is canceled. In the Response of 9/22/2025, claims 18, 21 and 35 are amended. In the Response of 3/6/2026, no claims are amended, canceled or added.
Claims 17-19, 21-22, 24-25, 27, 35 and 37 are all the claims under examination.
The Office Action contains new grounds for rejection.
Priority
2. USAN 16/499,723, filed 09/30/2019, and having 4 RCE-type filing therein is a National Stage entry of PCT/NL2018/050204, International Filing Date: 04/03/2018,
claims foreign priority to EP 17164382.8, filed 03/31/2017.
Information Disclosure Statement
3. As of 4/13/2026, a total of six (6) IDS are filed for this application: 7/29/2020; 11/5/2021; 12/27/2022; 5/16/2023; 9/22/2025; and 3/6/2026. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Rejections
Double Patenting
4. The rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11279770 is withdrawn for the pending claims. The ref patent claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
5. The rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12139548 is withdrawn for the pending claims. The ref patent claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
6. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 36, 40, 49, 51, 53-56 and 58-71 of copending Application No. 17/675,431 (reference application US 20220348683) is moot for the abandoned application as of 12/22/2025.
7. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 58-78 of copending Application No. 18/419,492 (reference application US 20240158531) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
8. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 58-68 and 70-73 of copending Application No. 18/419,527 (reference application US 20240158532) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
9. The rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11780925 is withdrawn for the pending claims. The patent ref claims recite none of the instant claimed features: the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
10. The rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12247078 is withdrawn for the pending claims. The patent ref claims recite none of the instant claimed features: the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
11. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18-21 of copending Application No. 18/449,460 (reference application US 20240199747) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
12. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 66-91 of copending Application No. 16/499,144 (reference application US 20210206875) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
13. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 16-21 of copending Application No. 17/755,196 (reference application US 20220372166) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
14. The provisional rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-7 of copending Application No. 18/251,832 (reference application US 20240026029) is withdrawn for the pending claims. The ref claims recite none of the instant claimed features: the ErbB-2/ErbB-3 positive tumor has at least 150,000 ErbB-2 cell-surface receptors per cell and a ratio of ErbB-2/ErbB-3 cell-surface receptors per cell of at least 10:1, and the subject has not previously been treated with a therapy that reduces the expression and/or activity of ErbB-2 and/or ErbB-3.
Claim Rejections - 35 USC § 103
15. The rejection of Claims 17-19, 21-22, 24-25, 27, 35 and 37 under 35 U.S.C. 103 as being obvious over Logtenberg et al (US 20240052043; priority 2/28/2014) in view of GEUIJEN et al (US 20170037145; priority 2/27/2015) is withdrawn.
New Grounds for Rejection
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.
The factual inquiries 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.
16. Claims 17-19, 21-22, 24-25, 27, 35 and 37 are rejected under 35 U.S.C. 103 as being obvious over Logtenberg et al (US 20240052043; priority 2/28/2014) in view of Maussang-Detaille et al (USPN 12,195,551 (Merus; 5/17/2017)) and GEUIJEN et al (US 20170037145; priority 2/27/2015).
AS regards claim 17 and 35, Logtenberg teaches and claims using a bispecific anti-ErbB-2 x anti-ErbB-3 antibody comprising the VH CDR1-3 from the MF3958 clone: AYYIN--RIYPGSGYTSYAQKFQG—PPVYYDSAWFAY; the VH CDR1-3 from the MF3178 clone: GYYMH—WINPNSGGTNYAQKFQG—DHGSRHFWSYWGEFDY (56); and the shared common light chain VLCDR1-3 from the IGKV1-39 clone (27):
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; methods of treating an ErbB-2+/ ErbB-3+ tumor: “The ErbB-3 antigen binding site binds ErbB-3 and a variety of variants thereof, such as those expressed by some ErbB-2 positive tumor cells.”
AS regards claims 17-19, Maussang-Detaille teaches methods of treating ErbB-2/ErbB-3 expressing breast cancer with a combination of a therapeutically effective amount of an ErbB-2/ErbB-3 bispecific antibody and endocrine therapy (Abstract) and inclusive use of the clone MF3958 (104-105). Maussang-Detaille teaches a cancer cell model derived from “treatment naïve” breast cancer cells for testing the antibody:
“Example 1
(16) Antitumor efficacy of an HER2/HER3 targeting antibody was determined in the context of a combination treatment together with an aromatase inhibitor. MCLA-128 was used as a preferred example of a bispecific Her2/Her3 targeting antibody. It was used as single agent and in combination with the aromatase inhibitor Letrozole. The hormone-dependent HBCx-34 patient-derived breast cancer xenograft model established in immunodeficient mice was used as an example of a breast cancer.
(17) The Human Tumor Xenograft Models
(18) Human tumor samples of various histological origins were obtained with informed consent from patients treated at cancer centers and established as transplantable xenografts in immunodeficient mice. The grafted samples are residual material from primary tumors or metastases obtained before or after treatment. These patient-derived xenograft (PDX) models have been established without prior in vitro culture and have been studied for histology, cytogenetics, genetic and other biological markers, and for their response to standard-of-care (SOC) therapies.
(19) The HBCx-34 PDX model was derived from a treatment-naïve primary breast infiltrating ductal carcinoma. The HBCx-34 PDX model has a mutated ATM (gene coding for a protein implicated in double strand DNA repair) and wt p53, is ER+/PR+, and is responder to Docetaxel, Capecitabine, Tamoxifen and the combination Adriamycin/Cyclophosphamide and low responder to Letrozole.
(20) The HBCx-34 tumor model takes about 35 days to obtain the maximum of tumors in the range 60 to 200 mm.sup.3 and about 80 days to reach 2000 mm.sup.3 from implantation day (with estrogen supplementation). HBCx-34 has got no overt cachectic properties, but not body weight gain is observed in HBCx-34-bearing mice.”
GEUIJEN re-iterates the use of a bispecific anti-ErbB-2 x anti-ErbB-3 antibody identical to Logtenberg (GEUIJEN at claims 21, 22 and 32-33) and further teaches targeting ErbB2/ErbB3 expressing cancer cells where the receptor density of ErbB-2/ErbB-3 is at least 150,000 ErbB-2
[0033] In a preferred embodiment the ErbB-2 and ErbB-3 positive cell comprises at least 50.000 ErbB-2 receptors on the cell surface. In a preferred embodiment at least 100.000 ErbB-2 receptors. In one preferred embodiment, the ErbB-2 and ErbB-3 positive cell comprises at least 1.000.000 ErbB-2 receptors on the cell surface. In another preferred embodiment the ErbB-2 and ErbB-3 positive cell comprises no more than 1.000.000 ErbB-2 receptors on the cell surface.
3. A bispecific antibody according to claim 2, wherein the antibody can reduce ligand-induced growth of an ErbB-2 and ErbB-3 positive cell, wherein said cell has at least 100.000 ErbB-2 cell-surface receptors per cell
GEUIJEN teaches a ErbB-2 and ErbB-3 positive cell ratio of 10:1 on an SKBR-3 cell (GEUIJEN claim 4).
As regards claims 21-22, GEUIJEN teaches a ErbB-2 and ErbB-3 positive cell ratio of 100:1 on an SKBR-3 or BT-474 cell and 4:10 on an MCF-7
[0228] Anti-HER2 titers in the serum from immunized C57B1/6 mice were determined by ELISA against ECD-Erbb-2 protein (Bendermedsystems) and FACS analysis on the HER2 negative K562, the HER2 low expressing cell line MCF-7 and HER2 amplified SKBR-3 and BT-474 cells. Anti-HER3 titers in the serum from immunized C57B1/6 mice were determined by ELISA against Erbb-3-Fc protein and FACS analysis on the HER3 negative K562, the HER2 low expressing cell line MCF-7 and HER2 amplified SKBR-3 and BT-474 cells.
AS regards claim 24, GEUIJEN teaches a ErbB-2 and ErbB-3 positive cell with <50,000 ErbB-3 receptors per cell on K562
[0228] Anti-HER2 titers in the serum from immunized C57B1/6 mice were determined by ELISA against ECD-Erbb-2 protein (Bendermedsystems) and FACS analysis on the HER2 negative K562, the HER2 low expressing cell line MCF-7 and HER2 amplified SKBR-3 and BT-474 cells. Anti-HER3 titers in the serum from immunized C57B1/6 mice were determined by ELISA against Erbb-3-Fc protein and FACS analysis on the HER3 negative K562, the HER2 low expressing cell line MCF-7 and HER2 amplified SKBR-3 and BT-474 cells.
AS regards 25, GEUIJEN teaches a ErbB-2 and ErbB-3 positive cell with <400,000 ErbB-1 receptors per cell
[0017] As used herein, antigen-binding refers to the typical binding capacity of an antibody to its antigen. An antibody comprising an antigen-binding site that binds to ErbB-2, binds to ErbB-2 and, under otherwise identical conditions, at least 100-fold lower to the homologous receptors ErbB-1 and ErbB-4 of the same species. An antibody comprising an antigen-binding site that binds to ErbB-3, binds to ErbB-3 and, under otherwise identical conditions, not to the homologous receptors ErbB-1 and ErbB-4 of the same species.
AS regards 27, GEUIJEN teaches administering an ErbB-1 inhibitor
[0004] The anti-ErbB-2 monoclonal antibody trastuzumab (Herceptin) and the ErbB-1 specific cetuximab (Erbitux) are among several monoclonal antibodies approved for clinical application.
AS regards claim 37, GEUIJEN teaches human subjects
[0020] …Preferably, an antibody of the present invention is of the human IgG1 subclass. Such antibodies of the invention have good ADCC properties, have favorable half life upon in vivo administration to humans and CH3 engineering technology exists that can provide for modified heavy chains that preferentially form heterodimers over homodimers upon co-expression in clonal cells.
[0132] The subject is preferably a human subject. The subject is preferably a subject eligible for monoclonal antibody therapy using an ErbB-2 specific antibody such as trastuzumab. In a preferred embodiment the subject comprises a tumor, preferably an ErbB-2/ErbB-3 positive cancer, preferably a tumor/cancer with an ErbB-2 therapy resistant phenotype and/or a heregulin resistance phenotype, preferably a monoclonal antibody resistant phenotype. A tumor involving such phenotype can escape treatment with a current anti-HER2 regimen, such as (but not limited to) monoclonal antibody therapy against ErbB-2.
The motivation to obtain signal regulatory functionalized antibodies that effectuate differential receptor binding effects is achieved by the combined reference art that teaches and appreciates, for example, those antibodies comprising a first antigen-binding site that binds Erb B-2 and a second antigen-binding site that binds ErbB-3 that can reduce a ligand-induced receptor function of ErbB-3 on a ErbB-2 and ErbB-3 positive cell. The reference combination teaches and demonstrates with working antibodies tested in working models to demonstrate the bispecific antibodies as a first line treatment for a subpopulation of patients having demonstrated improved effects over trastuzumab or pertuzumab.
Conclusion
17. No claims are allowed.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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