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 .
Priority
The present application claimed priority to the following applications: 63/142,566 and PCT/IL2022/050120, with effective filing dates of 28 January 2021 and 27 January 2022, respectively.
Claim Status
Applicant’s election of Group I (claims 1, 2, 4, 5, 9, 10, 12, 13, 17, 19, 23-26, and 29-33) and species of taxanes and breast cancer in the reply filed on 11 January 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 9, 10, 12, 13, 17, 29, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claim 39 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group (Group II: claim 39), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11 January 2026.
Claims 1, 2, 4, 5, 19, 23-26, 30, and 32-33 are pending.
Information Disclosure Statement
The Information Disclosure Statement filed on 13 May 2024 and the references cited therein have been considered, unless indicated otherwise.
Claim Interpretation
Claim 1 specifies a method of determining subject suitability for treatment with a microtubule targeting agent via measuring SETDB1 expression and administering the microtubule targeting agent to a suitable subject. For clarity, the Examiner interprets this to include measuring SETDB1 expression post administration of a microtubule agent to a subject. Further, the specification recites that a subject can be a biological sample ([064]).
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.
1. Claims 1 and 2 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a method of determining suitability of a subject in need thereof to be treated with a microtubule targeting agent (MTA), the method comprising receiving a sample from said subject, measuring SETDB 1 expression in said sample and determining suitability based on said SETDB 1 expression, thereby determining suitability of a subject to be treated with an MTA, the method further comprises administering said MTA to a suitable subject. Claim 2 further recites said MTA is a microtubule (MT) stabilizing agent and wherein any one of: (i) expression of SBTDB1 above a predetermined threshold indicates said subject is unsuitable for treatment with said MTA; and (ii) expression of SETDB1 at or below a predetermined threshold indicates said subject is suitable for treatment with said MTA, optionally wherein said predetermined threshold is an expression level in a healthy control.
However, the specification details a method for assessing microtubule-targeting agents on SETDB1 but does not detail SETDB1 level of expression in response to microtubule-targeting agent nor the predetermined threshold that is indicative of suitability for treatment with a microtubule-targeting agent (see the specification, pages 35, [0144]-[0145]).
The closest prior art, Emran (Oncotarget, 2018, 9(9), 8206-8222) teaches epigenetic reprogramming can lead to acquired drug resistance and identified early stress-induced multi-drug tolerant cancer cells in multiple cancer lines, such as breast cancer (abstract). Emran specifically teaches silencing of SETDB1 reverses drug tolerance and higher expression of SETDB1 in drug resistant models of cancer (abstract; page 8212 column 2, paragraph 1). Emran specifies that chronic exposure to docetaxel (a taxane, see the specification, page 4, [013]) at high concentrations led to a similar transition to the IDTC (induced drug-tolerant cells) state which involves SETDB1 up-regulation, which Emran teaches corresponds with higher expression of SETDB1 (page 8212, column 2, paragraph 1). Emran further teaches that SETDB1 up-regulation suggests increased expression of SETDB1, which stabilizes H3K9me3 and is characteristic across different cancer types as a generic response toward stress (page 8212, column 2, paragraph 1). Emran further specifies that silencing of SETDB1 restores drug sensitivity with dabrafenib due to a significant reduction of H3K9me3 and that knockdown inhibited the acquisition of induced drug tolerance (page 8212, column 2, paragraph 2). Emran further teaches that shSETDB1 cells exposed to high concentrations of docetaxel were sensitive to the small molecule (page 8212, column 2, paragraph 2). Because Emran demonstrated (1) chronic exposure of SETDB1 to docetaxel induces drug tolerance through stabilization of H3K9me3, (2) knockdown of SETDB1 reduces H3K9me3 and leads to inhibition of H3K9me3-mediated drug tolerance, and (3) docetaxel activity is restored in shSETDB1 (knockdown of SETDB1) at high concentrations of docetaxel, one of ordinary skill in the art would reasonably infer that docetaxel is able to treat a subject up to a certain, unspecified level of SETDB1 expression (page 8212, column 2, paragraphs 1 and 2).
Further, Batham (Cancers, 2019, 11(1143), 1-20) teaches treating breast cancer via microRNA, miR-381-3p, which successfully downregulated SETDB1 expression in a biological sample and that once SETDB1 expression was restored, SETDB1 overcame miRNA interference, indicating SETDB1 as a potential target for breast cancer therapy (page 13, paragraph 2). Batham underscores the unpredictability of the art in that there is some unspecified level of SETDB1 expression, in which an agent (such as a microtubule stabilizing agent) would be able to treat a subject.
Thus, the specification does not describe the claimed subject matter that would reasonably convey to one of skill in the art a method of determining suitability of a subject in need thereof to be treated with a microtubule targeting agent (MTA), the method comprising receiving a sample from said subject, measuring SETDB 1 expression in said sample and determining suitability based on said SETDB 1 expression, thereby determining suitability of a subject to be treated with an MTA, the method further comprises administering said MTA to a suitable subject.
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.
2. Claim 32 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 32 recites a method of treating a subject suffering from a SETDB1-associated cancer, the method comprising (i) reducing microtubule stability in said cancer characterized by increased expression and (ii) increasing microtubule stability in a cancer characterized by decreased or healthy SETDB1 expression, thereby treating said subject. Because claim 32 does not recite steps (i) and (ii) in the alternative, it is unclear how a microtubule stabilizing agent would be able to both reduce microtubule stability by increasing SETDB1 expression and increase microtubule stability by decreasing SETDB1 expression.
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.
3. Claim 30 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 30 recites a microtubule stabilizing agent that further comprises decreasing HDAC6 expression, function, or both in a suitable subject, which is an additional effect (and not an additional step). Because decreasing HDAC6 expression or function does not recite an additional step, claim 30 does not further limit claim 1.
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.
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.
4. Claims 1, 2, 4, 5, 24, 25, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Emran (Oncotarget, 2018, 9(9), 8206-8222) as evidenced by Wikipedia 1 (“Small Molecule,” Wikipedia, 2020, <https://web.archive.org/web/20200112030154/https://en.wikipedia.org/wiki/Small_molecule>, accessed 12 February 2026) and Wikipedia 2 (“Taxane,” Wikipedia, 2020, <https://web.archive.org/web/20200301173544/https://en.wikipedia.org/wiki/Taxane>, accessed 12 February 2026).
Emran teaches epigenetic reprogramming can lead to acquired drug resistance and identified early stress-induced multi-drug tolerant cancer cells in multiple cancer lines, such as breast cancer (abstract).
Emran specifically teaches silencing of SETDB1 reverses drug tolerance and higher expression of SETDB1 in drug resistant models of cancer (abstract; page 8212 column 2, paragraph 1). Emran specifies that chronic exposure to docetaxel (a taxane, see the specification, page 4, [013]) at high concentrations led to a similar transition to the IDTC (induced drug-tolerant cells) state which involves SETDB1 up-regulation, which Emran teaches corresponds with higher expression of SETDB1 (page 8212, column 2, paragraph 1). Emran further teaches that SETDB1 up-regulation suggests increased expression of SETDB1, which stabilizes H3K9me3 and is characteristic across different cancer types as a generic response toward stress (page 8212, column 2, paragraph 1). Emran further specifies that silencing of SETDB1 restores drug sensitivity with dabrafenib due to a significant reduction of H3K9me3 and that knockdown inhibited the acquisition of induced drug tolerance (page 8212, column 2, paragraph 2). Emran further teaches that shSETDB1 cells exposed to high concentrations of docetaxel were sensitive to the small molecule (page 8212, column 2, paragraph 2).
Because Emran demonstrated (1) chronic exposure of SETDB1 to docetaxel induces drug tolerance through stabilization of H3K9me3, (2) knockdown of SETDB1 reduces H3K9me3 and leads to inhibition of H3K9me3-mediated drug tolerance, and (3) docetaxel activity is restored in shSETDB1 (knockdown of SETDB1) at high concentrations of docetaxel, one of ordinary skill in the art would reasonably infer that docetaxel is able to treat a subject up to a certain, unspecified amount of SETDB1 (page 8212, column 2, paragraphs 1 and 2).
Regarding claim 1, Emran teaches a method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject (page 8212, column 2, paragraphs 1 and 2).
Regarding claim 2, Emran teaches a method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject (page 8212, column 2, paragraphs 1 and 2). Because Emran demonstrated (1) chronic exposure of SETDB1 to docetaxel induces drug tolerance through stabilization of H3K9me3, (2) knockdown of SETDB1 reduces H3K9me3 and leads to inhibition of H3K9me3-mediated drug tolerance, and (3) docetaxel activity is restored in shSETDB1 (knockdown of SETDB1) at high concentrations of docetaxel, one of ordinary skill in the art would reasonably infer that docetaxel is able to treat a subject up to a certain, unspecified amount of SETDB1 (page 8212, column 2, paragraphs 1 and 2). Thus, Emran teaches that there is a predetermined threshold of SETDB1 expression that indicates if a subject is suitable for treatment with a taxane.
Regarding claim 4, Emran teaches the microtubule stabilizing agent is docetaxel, which is a taxane (see the specification, page 4, [013]). Taxane is a small molecule as evidenced by Wikipedia 1 (“Small Molecule,” Wikipedia, 2020, <https://web.archive.org/web/20200112030154/https://en.wikipedia.org/wiki/Small_molecule>, accessed 12 February 2026) and Wikipedia 2 (“Taxane,” Wikipedia, 2020, <https://web.archive.org/web/20200301173544/https://en.wikipedia.org/wiki/Taxane>, accessed 12 February 2026). Wikipedia 1 teaches that terpenes are small molecules (page 2, paragraph 3), and Wikipedia 2 teaches that taxanes are a class of diterpenes (page 1, paragraph 1).
Regarding claim 5, Emran teaches a microtubule stabilizing agent is docetaxel, which is a taxane (see the specification, page 4, [013]).
Regarding claim 24, Emran teaches the sample is a tumor sample (page 8212, column 2, paragraphs 1 and 2).
Regarding claim 25, Emran teaches that the expression is protein expression (abstract).
Regarding claim 30, Emran teaches the microtubule stabilizing agent, docetaxel, and its effect relative to SETDB1 expression (page 8212, column 2, paragraphs 1 and 2). As Applicant does not further specify a certain concentration dosage of a taxane for decreasing HDAC6 expression or function, claim 30 does not specify an additional step but does specify an additional effect. Thus, claim 30 merely recites an additional effect of a claimed method. Consequently, Emran teaches the claimed method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject (page 8212, column 2, paragraphs 1 and 2). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Thus, Emran teaches the microtubule stabilizing agent, docetaxel, and its effect relative to SETDB1 expression that decreases HDAC6 expression or function.
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.
5. Claims 19, 23, 26, 32, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Emran (Oncotarget, 2018, 9(9), 8206-8222) as evidenced by Wikipedia 1 (“Small Molecule,” Wikipedia, 2020, <https://web.archive.org/web/20200112030154/https://en.wikipedia.org/wiki/Small_molecule>, accessed 12 February 2026) and Wikipedia 2 (“Taxane,” Wikipedia, 2020, <https://web.archive.org/web/20200301173544/https://en.wikipedia.org/wiki/Taxane>, accessed 12 February 2026) in view of Batham (Cancers, 2019, 11(1143), 1-20).
Emran (Oncotarget, 2018, 9(9), 8206-8222) as evidenced by Wikipedia 1 (“Small Molecule,” Wikipedia, 2020, <https://web.archive.org/web/20200112030154/https://en.wikipedia.org/wiki/Small_molecule>, accessed 12 February 2026) and Wikipedia 2 (“Taxane,” Wikipedia, 2020, <https://web.archive.org/web/20200301173544/https://en.wikipedia.org/wiki/Taxane>, accessed 12 February 2026) are applied as discussed in the 35 U.S.C. 102 rejection above.
The Examiner notes the relevant teachings with respect to claims 1, 2, 4, 5, 24, 25, and 30 are set forth above and are incorporated herein by reference.
Additional relevant teachings are set forth below.
Emran teaches a method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject (page 8212, column 2, paragraphs 1 and 2).
Emran further teaches upregulation of SETDB1 in WM1366 (melanoma), WM164 (melanoma), A549 (lung), and HT29 (colon) cancer cell lines (page 8207, column 2, paragraphs 1 and 2; page 8212, column 2, paragraph 1).
Regarding claim 19, Emran fails to teach treating breast cancer in a biological sample via administering a taxane and measuring SETDB1 expression.
Batham teaches treating breast cancer via microRNA, miR-381-3p, which successfully downregulated SETDB1 expression in a biological sample and that once SETDB1 expression was restored, SETDB1 overcame miRNA interference, indicating SETDB1 as a potential target for breast cancer therapy (page 13, paragraph 2).
It would have been prima facie obvious to one or ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the method of Emran with the method of treating breast cancer of Betham to develop a method of treating breast cancer via administration of taxane and measuring SETDB1 expression, to arrive at instant claim 19. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Emran teaches epigenetic reprogramming can lead to acquired drug resistance and identified early stress-induced multi-drug tolerant cancer cells in multiple cancer lines, such as breast cancer,
-Emran teaches silencing of SETDB1 reverses drug tolerance and that there was higher expression of SETDB1 in drug resistant models of cancer,
-Emran teaches that chronic exposure to docetaxel (a taxane, see the specification, page 4, [013]) at high concentrations led to a similar transition to the IDTC (induced drug-tolerant cells) state which involves SETDB1 up-regulation, which corresponds with higher expression of SETDB1,
-Emran teaches that SETDB1 up-regulation suggests increased expression of SETDB1 stabilizes H3K9me3, which is characteristic across different cancer types as a generic response toward stress,
-Emran teaches that silencing of SETDB1 restores drug sensitivity with dabrafenib due to a significant reduction of H3K9me3 and that knockdown inhibited the acquisition of induced drug tolerance,
-Emran teaches that shSETDB1 cells exposed to high concentrations of docetaxel were sensitive to the small molecule,
- Emran teaches a method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject,
-Batham teaches treating breast cancer via microRNA, miR-381-3p, which successfully downregulated SETDB1 expression in a biological sample and that once SETDB1 expression was restored, SETDB1 overcame miRNA interference, indicating SETDB1 as a potential target for breast cancer therapy,
-Batham teaches SETDB1 and its role in breast cancer metastasis serves as an exemplar of the difficulties faced when developing therapies that target cancer cells and the more elusive and aggressive stem cells that contribute to metastasis (abstract),
-Batham teaches breast cancer is the most common cancer in women over the age of 50 (page 1, paragraph 1),
-Batham teaches SETDB1 is responsible for the di- and tri-methylation of histone H3 lysine 9 in euchromatic regions to promote gene silencing through heterochormatin formation (page 2, paragraph 4), and
-Batham teaches the structural and functional dynamic of the SETDB1 enzyme in cell dysregulation is not well characterized, illustrates the SETDB1 epigenetic activity in breast cancer tissues, and reviews the biology of SETDB1 and its interacting partners (page 3, paragraph 2).
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection, to predictably arrive at a method of treating breast cancer via administration of taxane and measuring SETDB1 expression.
Regarding claim 23, Batham teaches the cancer is breast cancer (page 13, paragraph 2).
Regarding claim 26, Batham teaches SETDB1 expression is cytoplasmic SETDB1 expression (page 6, paragraph 3).
Regarding claim 32, claim 32 defines that reducing microtubule stability in SETDB1-associated cancer is characterized by increased expression of SETDB1 and the converse: increasing microtubule stability in a SETDB1-associated cancer is characterized by decreased SETDB1 expression. Emran teaches a method of treating a subject having a SETDB1-associated cancer and measuring SETDB1 expression (page 8212, column 2, paragraphs 1 and 2). Further, Batham teaches a method of treating breast cancer via microRNA, miR-381-3p, which successfully downregulated SETDB1 expression in a biological sample and that once SETDB1 expression was restored, SETDB1 overcame miRNA interference, indicating SETDB1 as a potential target for breast cancer therapy (page 13, paragraph 2). Thus, Emran and Batham teach a method of treating a subject suffering from breast cancer, the method comprising increasing microtubule stability in breast cancer characterized by decreased SETDB1 expression, thereby treating said subject.
Regarding claim 33, Emran teaches administering a docetaxel (a taxane) that increases microtubule stability, which is characterized by decreased SETDB1 expression (as defined by claim 32; page 8212, column 2, paragraph 2). Additionally, as Applicant does not further specify a certain concentration dosage of a taxane for decreasing HDAC6 expression or function, claim 33 does not specify an additional step but does specify an additional effect. Thus, claim 33 merely recites an additional effect of a claimed method. Consequently, Emran teaches the claimed method of treating a subject via administering a taxane and measuring SETDB1 expression in a sample from the subject (page 8212, column 2, paragraphs 1 and 2). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Thus, Emran teaches the microtubule agent, docetaxel, that increases microtubule stability and decreases HDAC6 expression or function.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Madeline M Dekarske whose telephone number is (571)272-1789. The examiner can normally be reached Monday - Thursday 10am - 4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached at 571-272-5548. 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.
/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622