DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment, filed 10 April 2024, has been entered in full. Claims 16, 18, 19, 22, 23 and 25 are canceled. Claims 17, 20, 21, 24 and 26 are amended.
Claims 1-15, 17, 20, 21, 24 and 26 are under examination.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 4/10/2024 and 10/8/2025) were received and comply with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. They have been placed in the application file and the information referred to therein has been considered as to the merits.
Foreign Priority
Acknowledgment is made of Applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d). The certified copy PCT/CN022/124968 (10.12.2022) has been placed of record in the file.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description:
The Drawings recite Figure 1A-B; 4A-J; 5A-G; 7A-D; 8A-E; 9A-C; 11A-B; 13A-B; 14A-B and 15A-B, but the reference character(s) are not mentioned in the description.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 14, 15, 17, 21 and 24 are objected to because of the following informalities:
In claim 14, the four recitations of “an amino acid sequence” should be amended to “the amino acid sequence”
In claim 15, the two recitations of “an amino acid sequence” should be amended to “the amino acid sequence”
Claim 17 should be amended to recite, “..comprising the anti-CD3 antigen-binding fragment thereof of claim..”
Claim 21 should be amended to recite, “One or more isolated polynucleotide(s) encoding..”
Claims 21 and 24 should be amended to recite, “..or antigen-binding fragment thereof..”
Claim 24 should be amended to recite, “..administering to a cancer patient..”
Appropriate 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.
Claims 24 and 26 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The instant specification teaches anti-CD3 (cluster of differentiation 3) antibodies, including humanized ones, and their antigen-binding fragments. The specification teaches that the anti-CD3 antibodies and fragments can be suitably used in bi- or tri-specific antibodies to achieve optimized activities and safety margins (abstract).
The Examples teach the generation of anti-human CD3 monoclonal antibodies and the binding of the antibodies to CD3 antigen.
Example 19 teaches B16F10 is a mouse melanoma cell line derived from the pulmonary melanoma nodule. B16F10-h5T4 cells were injected into CD3/4-1BB humanized mice. Treatments started when the tumor size reached 100 mm.sup.3. The Example teaches the 155-8 based trispecific antibody (CTM01-01). The Example teaches treatment with CTM01-01 (wild-type trispecific antibody targeting CD3, 4-1BB and human 5T4 as the TAA) resulted in dramatic tumor reduction. The Example teaches by contrast, the treatment with CTM01-01B, in which the anti-CD3 portion was inactivated, did not have a significant effect, and the treatment with CTM01-01A, in which the anti-4-1BB portion was inactivated, had only suboptimal efficacy (paras 0289-0292).
The instant claims are not enabled for the following reasons:
1. Example 19 teaches B16F10 as a mouse melanoma cell line derived from the pulmonary melanoma nodule. B16F10-h5T4 cells were injected into CD3/4-1BB humanized mice. The Example teaches treatment with CTM01-01 (wild-type trispecific antibody targeting CD3, 4-1BB and human 5T4 as the TAA) resulted in dramatic tumor reduction.
However, claims 24 and 26 fail to recite administering a trispecific antibody that specifically binds CD3, 4-1BB and human 5T4, wherein the trispecific antibody comprises:
VH CDR1, VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3 for CD3 binding and
VH CDR1, VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3 for 4-1BB binding and
VH CDR1, VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3 for human 5T4 binding
2. The instant claims are drawn to a method of treating cancer in a subject. Cancer encompasses diverse cancers such as brain cancer, cervical cancer, breast cancer, colon cancer, leukemia, etc.
However, the employed mouse melanoma animal model would not be tantamount or any way correlative with in vivo treatments for all cancers.
See wherein Hassanpour et al. teach that cancer in the broader sense refers to more than 277 different types of cancer disease. Hassanpour et al. teach that cancer is a variety disease at the tissue level. Hassanpour et al. teach that this variety is a major challenge for its specific diagnosis, followed by efficacy of treatment. Hassanpour et al. teach scientists have stated several gene mutations are involved in cancer pathogenesis; also included are chemical compounds, environmental chemical substances with carcinogenic properties, viruses, bacteria and radiation rays (Hassanpou et al. Review of cancer from perspective of molecular. Journal of Cancer Research and Practice. Volume 4:127-129; available July 2017).
Upadhyay teaches that intratumor heterogeneity (i.e., extreme genetic diversity among cell populations residing in the same tumor mass), leads to Darwinian principles and natural selection forces to work on it and establish a more robust variety of cancer cells. Upadhyay teaches that this heterogeneity increases drug resistance and thus poses a great therapeutic challenge before clinicians in developing cancer treatment (page 657)(Upadhyay, A. Cancer: An unknown territory; rethinking before going ahead. Genes & Diseases Volume 8:655-661, 2021; available online 18 Sept 2020).
Justice et al. teach, “It seems an obvious point, but the model used should be appropriate for the question being addresses. An ideal disease model accurately mimics the human condition, genetically, experimentally and/or physically”. Justice et al. teach that in one example, data from human blunt-trauma patients were analyzed together with data from a mouse inbreed strain that had been exsanguinated. Justice et al. teach, “Losing a large amount of blood does not equate to blunt trauma, and so this could be perceived as comparing apples to oranges” (page 101, 2nd column 2nd full paragraph). Justice et al. teach that in a different study, a mouse model was reported to display the key motor symptoms seen in humans with amyotrophic lateral sclerosis (ALD). On the basis of this, the model was used in preclinical trial studies and promising drugs candidates were tested in clinical trials; however, the drugs ultimately failed in humans. It was shown that the particular mouse is a poor genetic and phenotypic model of human conditions. Justice et al. state, “This example illustrates how relevance to the human disease being studied, supported by strong data to validate the use of the model is crucial for clinical translation” (page 102, left column, 1st full paragraph)(Justice et al. Using the mouse to model human disease: increasing validity and reproducibility, Disease, Models & Mechanisms 9:101-103, 2016).
Due to the inherent unpredictability regarding treating any/all cancers comprising administering the claimed antibody to a cancer patient; the lack of direction/guidance presented in the specification regarding same; the absence of working examples directed to same; the complex nature of the invention; the state of the prior art which teach the use of proper animal models to discern treatment, that cancer in the broader sense refers to more than 277 different types of cancer disease, that cancer is a variety disease at the tissue level, which is a major challenge for its specific diagnosis, followed by efficacy of treatment and that there is extreme genetic diversity among cell populations residing in the same tumor mass; undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
Allowable Subject Matter
Claims 1-13 and 20 are allowable.
Claims 14, 15, 17, and 21 will be allowable once the claim objections are addressed.
Closest Prior Art
The closest prior art is Attar et al. (US Patent No. 10,562,968. Published Feb 18, 2020, priority date July 20, 2016). Attar et al. teach an antibody that binds CD3, wherein the VH CDR1 comprises an amino acid sequence that is 100% identical to instant SEQ ID NO:13. See below, Sequence Search Result A.
However, Attar et al. do not teach wherein the antibody comprises the recited sequences of the SEQ ID NOs for VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3.
Conclusion
Claims 14, 15, 17, 21 are objected to.
Claims 24 and 26 are rejected.
Claims 1-13 and 20 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.M.D/Examiner, Art Unit 1647 8/18/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
SEQUENCE SEARCH RESULT A
This page gives you Search Results detail for the Application 18700235 and Search Result 20260727_170709_us-18-700-235-13.minpct99.rai
Title: US-18-700-235-13
Perfect score: 29
Sequence: 1 SYNVH 5
Database : Issued_Patents_AA:*
SUMMARIES
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
Cancer Neoepitopes
6 29 100.0 10 US-15-655-086-66 2017-07-20 2 ANTI- GPRC5D ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND GPRC5D AND CD3, AND USES THEREOF
RESULT 6
US-15-655-086-66
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 66, US/15655086
Patent No. 10562968
GENERAL INFORMATION
APPLICANT: JANSSEN PHARMACEUTICA NV
TITLE OF INVENTION: ANTI- GPRC5D ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES
TITLE OF INVENTION: THAT BIND GPRC5D AND CD3, AND USES THEREOF
FILE REFERENCE: PRD3422USNP
CURRENT APPLICATION NUMBER: US/15/655,086
CURRENT FILING DATE: 2017-07-20
PRIOR APPLICATION NUMBER: 62/364,811
PRIOR FILING DATE: 2016-07-20
NUMBER OF SEQ ID NOS: 100
SEQ ID NO 66
LENGTH: 10
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 29; Length 10;
Best Local Similarity 100.0%;
Matches 5; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SYNVH 5
|||||
Db 6 SYNVH 10
Prosecution Insights