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
Filing Receipt
The filing receipt mailed 05/07/2024 states that the instant application is a 371 of PCT/US2022/032952, filed 06/10/2022, which claims benefit of provisional applications 63/257,634, filed 10/20/2021, 63/228,799, filed 08/03/2021, and 63/209,290, filed 06/10/2021. The provisional application 63/209,290 supports the instant claims. Therefore, the effective filing date is 06/10/2021.
Information Disclosure Statement
The information disclosure statement received 12/06/2023 has been considered.
Claim Objections
Claim 4 states “…characterized by data selected from one or more of the following:….h) combinations of these data.” The use of “h) combinations of these data” is redundant.
Rejections
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, does not reasonably provide enablement for the treatment of cancer generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The following Wands factors have been considered if not explicitly discussed: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims
Claim 14 claims “A method of treating cancer, comprising administering a therapeutically effective amount of a crystalline product according to claim 3, to a subject in need of the treatment.”
“Cancer” is not explicitly defined in the instant specification. No specific cancers are contemplated in the instant specification. The broadest reasonable interpretation includes all cancers.
Nature of the Invention
The invention is to a clinical method of treating cancers.
Amount of Direction and Working Examples
The instant disclosure does not provide evidence that the specific abexinostat tosylate form T1 in effective in treating any cancers. There are no working examples and there is no discussion regarding the use of abexinostat tosylate as an effective anti-cancer compound. The instant disclosure in para. [0003] states “Abexinostat is a hydroxamate-containing histone deacetylase (HDAC) inhibitor, and it is developed for the treatment of cancer.”
Additionally, where the art discusses non-Hodgkin lymphoma and chronic lymphophatic leukemia (see below), the instant specification is silent on these specific cancers. There is no evidence that the abexinostat tosylate crystal is effective as an anti-cancer agent against these cancers and there is discussion that would enable the instant claims as anti-cancer agents against these cancers.
State of the Prior Art
Abexinostat (free base) is well known within the art and abexinostat tosylate is mentioned in Astor (Targeted Oncology, FDA Grants Fast Track Designation to Abexinostat for Fourth-Line Follicular Lymphoma, published 2019, url= https://www.targetedonc.com/view/fda-grants-fast-track-designation-to-abexinostat-for-fourthline-follicular-lymphoma, accessed 01/28/2026). Astor states “A phase II study of abexinostat in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and chronic lymphophatic leukemia (CLL) showed a modest overall response rate (ORR), but a higher ORR was seen in patients with follicular lymphoma.” The difference between this statement and the instant disclosure is that the instant disclosure is the tosylate salt form of abexinostat.
Level of Predictability
The prior art enables abexinostat and its crystalline forms for at least NHL and CLL, but the instant closure does not sufficiently enable one skilled in the art to practice a method of treating cancer with the specific crystalline form T1. One of ordinary skill is not enabled to practice the claimed method with a reasonable level of predictability.
Note: The specification has support for general cancer but does not have support for the specific cancers mentioned above. Astor is cited simply to summarize the state of the art.
Written Description
Claim 4 is 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 4 states “A crystalline product according to claim 3, designated From T1, which is characterized by data selected from one or more of the following:…a 13C ssNMR spectrum having peaks at 165.23, 164.36, 138.74, 69.00, 44.74, 40.65, and 38.36 ppm ± 0.2 ppm; an 13C ssNMR spectrum as depicted in Figure 23…”. NMR spectra are not sufficient to distinct one crystalline form from another. A 13C NMR of an amorphous from abexinostat tosylate would be identical to a crystalline form.”
Claim Rejections - 35 USC § 112(d)
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 5 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 5 states “A crystalline product according to claim 4, designated Form T1, characterized by the XRPD pattern having peaks at 7.4, 8.6, 12.1 and 22.4 degrees 2-theta ±.0.2 degrees 2-theta, and also having one, two, three, or four additional peaks selected from 16.9, 17.3, 20.6, 21.7, and 26.0 degrees [2] theta ±0.2 degrees theta.”
This is supported by the specification in para. [00144], below.
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160
620
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Greyscale
The additional peaks are present in both figures 9 and 19. Therefore, the peaks are not impurities or other crystalline forms. The peaks belong to the specific crystalline form. Claim 4 claims a specific crystalline form T1, which includes the additional peaks into claim 4. Because of this, claim 5 is not further limiting.
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.
Allowable Subject Matter
Claims 1-3, 6-9, and 11-12 are allowed.
The closest art found in Pimont-Garro (US9,115,108, published 2015) discloses similar forms of abexinostat tosylate that have a specific XRPD. However, this form(s) does not have the same peaks or peaks within error of the instantly claimed crystalline form. Therefore the art cannot be applied.
Conclusion
Claims 4-5 and 14 are rejected.
Claims 1-3, 6-9, and 11-12 are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUISALBERTO GONZALEZ whose telephone number is (571)272-1154. The examiner can normally be reached M-F 8:30-5:30.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624