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 of Species and Status of the Claims
Applicant’s election without traverse of CCT251921 as the single specific CDK19 inhibitor in the response filed on December 11th 2025 is acknowledged. Claims 1-5, 7-11, and 16-25 are pending. Claims 9, 11, 19, and 24-25 are withdrawn from further consideration as being directed towards nonelected species (claims 9 and 24 require that the agent binds outside of the ATP binding site, in contrast to CCT-251921, which binds at the ATP binding site1; claims 11, 19, and 25 explicitly excludes CCT251921). Claims 1-5, 7-8, 10, 16-18, and 20-23 are examined on their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements filed on January 26th 2026, July 10th 2024, July 13th 2023, November 15th 2022, and September 13th 2022 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Minor Informalities
Examiner notes the presence of typographical errors in the claims, including the phrase “reduces to number of EpCAMmed/high…” in claim 2 (which will be interpreted as “reduces the number of EpCAMmed/high…” Review of the claims and appropriate corrections are required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 4-5, 7-8, and 16-19 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.
Claim 1 and its dependent claims 4-5, 7-8, 10, and 16-17 are indefinite for the phrase “wherein administration of the agent results in at least one of a reduction in cachexia, increase in survival time, elongation in time to tumor progression, reduction in tumor mass, reduction in tumor burden, prolongation in time to tumor metastasis, a prolongation in time to tumor recurrence, tumor response, complete response, partial response, stable disease, progressive disease, or progression free survival,” because one of ordinary skill in the art could not reasonably determine how the phrase further limits the method of claim 1. The phrase does further limit the CDK19 inhibitors administered, the composition in which they are administered, the dosage, the method of administration, the patient population, or any other aspect of the method of claim 1, but only the result of the method. The specification repeats the claim language (specification, paragraphs [0006], [0076]), but gives no indication as to how any of the described aspects of the method must be further limited in order to achieve said result (i.e. how the variance in any of the inhibitors, composition details, dosage, method, or patient population will achieve the desired results described by the method of claim 1).
As one of ordinary skill in the art could not reasonably determine how the above phrase further limits the method of claim 1, claim 1 and its dependent claims 4-5, 7-8, 10, and 16-17 are indefinite.
Similarly, claim 2 and its dependent claims 18-19 are indefinite for the phrase “wherein the treatment reduces the number of EpCAMmed/high and CD10-/low cells in the tumor, reduces the number of EpCAMmed/high and CD10-/low cells per unit volume of the tumor, or results in a reduction of the ratio of EpCAMmed/high and CD10-/low epithelial cells to normal cells in the tumor,” because one of ordinary skill in the art could not reasonably determine how the phrase further limits the method of claim 2. The phrase does further limit the CDK19 inhibitors administered, the composition in which they are administered, the dosage, the method of administration, the patient population, or any other aspect of the method of claim 1, but only the result of the method. The specification repeats the claim language (specification, paragraph [0006]), but gives no indication as to how any of the described aspects of the method must be further limited in order to achieve said result (i.e. how the variance in any of the inhibitors, composition details, dosage, method, or patient population will achieve the desired results described by the method of claim 2).
As one of ordinary skill in the art could not reasonably determine how the above phrase further limits the method of claim 2, claim 2 and its dependent claims 18-19 are indefinite.
Claim 5 is indefinite for the phrase “comprising detecting EpCAMmed/high / CD10-/low cells in a tissue sample from the patient after initiating therapy”, because it is unclear how the phrase further limits the method of claim 1. Specifically, the additional limitation, that the biomarker is detected after the initiation of the therapy, necessitates that the therapy is already being performed. Thereby, the phrase, which appears to limit the patient population receiving the therapy in the case where such a biomarker is detected prior to the initiation of the therapy, does not provide such a limitation wherein the biomarker is detected after the initiation of the therapy. Therefore, it is unclear how the phrase further limits the method of claim 1, and claim 5 is indefinite.
Claim 17 is further indefinite for the phrase “comparing the quantity of EpCAMmed/high/CD10-/low cells in (a) to a reference value characteristic of tumors responsive to a CDK19 targeting therapy,” because one of ordinary skill in the art could not reasonably determine the metes and bounds of the claim. Specifically, such a “reference value,” is not found in the specification, but only described in language identical to the claim language (specification, paragraphs [0019], [0138], [0156]). The specification states that:
“The reference value can be determined by quantitating EpCAMmed/high/CD10-/low cells in healthy and TNBC populations and calculating statistically significant ranges characteristic of healthy and tumor tissues. In another approach tumor tissue and healthy tissue from the same subject can be tested, and subjects with elevated EpCAMmed/high/CD10-/low cells can be identified as likely to respond to CDK19 targeted therapy.”
[specification, paragraph [00156]]
The specification describes a method of determining a reference range in order to classify “healthy” and “tumor” tissues, but gives no indication as to how to determine a single value which must be exceeded to identify a tumor as “responsive to CDK19 targeted therapy.” As one of ordinary skill in the art could not determine such a reference value without undue experimentation (i.e. no aspects of the reference determination are found in the specification, other than that the range of characteristic tissues must be ‘statistically significant,’ and that tumor cells with EpCAMmed/high/CD10-/low cells can be identified as likely to respond to CDK19 targeted therapy). The reference value cited in claim 17 is therefore unclear, and consequently both the patient population and claim 17 itself are indefinite.
Claim 17 is further indefinite for failing to further limit the scope of claim 1, upon which it depends. Claim 17 is directed to “a method of predicting the likely therapeutic responsiveness of a subject with TNBC to the method of treatment of claim 1.” Claim 17 then describes “treating the patient with the agent that inhibits expression or activity of cyclin-dependent kinase 19 (CDK19) if the quantity of EpCAMmed/high/CD10-/low cells is equal to or exceeds” a reference value. The described treatment limitation is left open-ended, however, in that no particular action (treatment or otherwise) is described in the situation wherein the quantity of EpCAMmed/high/CD10-/low cells is below the reference value.
Furthermore, if the claim is interpreted to require that the treatment is not performed in the situation wherein the quantity of EpCAMmed/high/CD10-/low cells is below the reference value, then the method of claim 17 will necessarily be outside the metes and bounds of the method of claim 1 (which requires that the method is performed). As it is unclear how the method of claim 17 further limits the method of claim 1, claim 17 is indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 7-8, 10, 16, 18, and 21-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Robinson (US 20170071942A1 published on March 16th 2017).
Claim 1 is directed towards the treatment of triple-negative breast cancer (TNBC) via administration of a CDK19 inhibitor wherein the treatment results in a prolongation in time to tumor metastasis. Claim 1 is anticipated by Robinson, who teaches the slower development of triple negative breast cancer tumors after treatment with the CDK19 inhibitor, Senexin B (Robinson, pg. 9, paragraph [0081]).
Claim 2 is directed towards the treatment of TNBC characterized by EpCAMmed/high and CD10-/low epithelial cells, via administration of a CDK19 inhibitor, wherein the treatment results in the reduction of the ratio of EpCAMmed/high and CD10-/low epithelial cells to normal (noncancerous) cells in the tumor. Robinson teaches the treatment of breast cancer epithelial cells (specifically MDA-MB-468), and the reduction of tumor size (which would necessarily result in a lower ratio of MDA-MB-468: normal cells) with Senexin B (Robinson, Figure 9B). As MDA-MB-468 is known as EpCAMhigh and CD10low, 23 Robinson’s method is anticipatory of claim 2.
Claim 3 is directed towards a method of reducing metastasis of TNBC in a patient comprising administration of a small molecule CDK19 inhibitor. Claim 3 is anticipated by Robinson, who teaches the slower development of triple negative breast cancer tumors after treatment with the CDK19 inhibitor, Senexin B (Robinson, pg. 9, paragraph [0081]).
Claim 4 requires that, in the method of claim 1, the patient is additionally administered a chemotherapy. Robinson teaches administration alongside doxorubicin (Robinson, pg. 10, paragraph [0090]), anticipating claim 4.
Claims 7 and 8 require that, in the method of claim 1, the agent binds to/inhibits expression of CDK19 to a greater degree than CDK8. As Senexin B satisfies these limitations (Robinson, Figure 5), Robinson anticipates claims 7-8.
Claim 10 requires that, in the method of claim 3, the agent binds to CDK19 to a greater degree than CDK8. As Senexin B satisfies this limitation (Robinson, Figure 5), Robinson anticipates claim 10.
Claim 16 requires that, in the method of claim 1, the agent binds CDK19 in the cytoplasm of a breast epithelial cell. Robinson teaches the binding of Senexin B to CDK19 (Robinson, Figure 5), and the treatment of breast cancer epithelial cells (specifically MDA-MB-468) with Senexin B (Robinson, Figure 9A). Robinson thereby anticipates claim 16.
Claim 18 requires that, in the method of claim 2, the agent binds to CDK19 to a greater degree than CDK8. As Senexin B satisfies this limitation (Robinson, Figure 5), Robinson anticipates claim 18.
Claims 21 and 22 require that, in the method of claim 3, the agent binds to/inhibits expression of CDK19 to a greater degree than CDK8. As Senexin B satisfies these limitations (Robinson, Figure 5), Robinson anticipates claims 21-22.
Claim 23 requires that, in the method of claim 3, the agent binds to the ATP binding site of CDK19. As Senexin B is known in the art to be an ATP competitive binder4 (note that the binding properties of the compound do not change, regardless of when the properties are discovered/described), Robinson anticipates claim 23.
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, 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.
Claims 5, 17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson (US 20170071942A1 published on March 16th 2017).
Claim 5 is directed towards the method of claim 1, comprising detecting EpCAMmed/high and CD10-/low cells in a tissue sample from the patient before or after initiating therapy. For the teachings of Robinson as they are relevant to claim 1, see the above 102 rejection for claim 1. It is noted that the detection of the particular protein expression does not meaningfully limit the patient population (i.e. narrowing of a patient population to a subpopulation is obvious absent evidence of unexpected results, critically in said subpopulation, or wherein the broader patient population is taught away). Furthermore, the detection of the protein expression pattern in the sample after the initiation of therapy necessitates that the therapy is already being performed. Thereby, one of ordinary skill in the art would reasonably treat the patient population described in claim 5, and claim 5 is prima facie obvious.
Claim 17 is directed towards a method of predicting the likely therapeutic response of a subject with TNBC to the method of treatment of claim 1, comprising performing treatment if a detected amount of EpCAMmed/high and CD10-/low cells in a tumor sample exceeds a reference value characteristic of tumors responsive to CDK19 therapy. For the teachings of Robinson as they are relevant to claim 1, see the above 102 rejection for claim 1. It is noted that (as described in the above 101 rejection), the detection of the particular protein expression does not meaningfully limit the patient population (i.e. narrowing of a patient population to a subpopulation is obvious absent evidence of unexpected results, critically in said subpopulation, or wherein the broader patient population is taught away). Thereby, one of ordinary skill in the art would reasonably treat the patient population described in claim 17, and claim 17 is prima facie obvious.
Claim 20 is directed towards the method of claim 3, comprising detecting EpCAMmed/high and CD10-/low cells in a tissue sample from the patient before or after initiating therapy. For the teachings of Robinson as they are relevant to claim 3, see the above 102 rejection for claim 3. It is noted that (as described in the above 101 rejection), the detection of the particular protein expression does not meaningfully limit the patient population (i.e. narrowing of a patient population to a subpopulation is obvious absent evidence of unexpected results, critically in said subpopulation, or wherein the broader patient population is taught away). Thereby, one of ordinary skill in the art would reasonably treat the patient population described in claim 20, and claim 20 is prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 (Mallinger et al., Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19 Journal of Medicinal Chemistry 2016 59 (3), 1078-1101)
2See Jenkinson, who describes the EPCAM-high characterization of MDA-MB-468 cells: Jenkinson et al., Functional effects of EpCAM N-glycosylation in MDA-MB-468 breast cancer cells. Sci Rep 16, 10021 (2026)
3 See Iglesias, who describes the expression of many proteins, including CD10 in breast cancer cells, including MDA-MB-468: Iglesias et al., (2013) Mammosphere Formation in Breast Carcinoma Cell Lines Depends upon Expression of E-cadherin. PLOS ONE 8(10)
4 For evidentiary support, see Zhang et al., A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor-Enriched Pharmacokinetics. J Med Chem. 2022 Feb 24;65(4):3420-3433
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