DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claim 1 is objected to because the first occurrence of each of abbreviations “HDAC,” “QTc,” and “QTcF” is not accompanied by the term it represents.
3. 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.
4. Claims 1-8 and 10-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite in the recitation of “a subject,” because the subject population is not defined.
(ii) Claim 1 is further indefinite in the recitation of “an effective amount,” because the nature of the relevant “effect” is unknown.
(iii) Claims 5-7 are indefinite, because the relationship, if any, between HDACs defined as “class I” and “class IIb,” and HDACs defined as “HDAC1,” “HDAC2,” “HDAC3” and “HDAC10” is not defined.
(iv) Claim 6 is indefinite as being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 803.02.
(v) Claim 10 is indefinite in the recitation of “the cancer,” because the recitation lacks proper antecedent basis in the base claim.
(vi) Claim 14 is indefinite in the recitation of “a cycle” because, in the absence of an indication of the length of a cycle, it is unclear how the recitation limits the scope of the claim.
(vii) Claims 2-8 and 11-20 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. The following is a quotation of 35 U.S.C. 112(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.
6. Claim 6 is rejected under 35 U.S.C. 112(d) 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 6 depends on claim 5 which is limited to HDACi which inhibit both class I and class IIb HDACs, whereas claim 6 encompasses HDACi which inhibit one of HDAC1 and HDAC2 (assuming that HDAC1 and HDAC2 are the same as class I and class II HDACs, respectively – see subsection 4(iii) above).
Therefore, dependent claim 6 may be infringed without infringing the base claim, and as such, claim 6 fails to further limit, and fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place it in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
7. The following is a quotation 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.
8. Claims 1-7 and 9-20 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain 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, at the time the application was filed, had possession of the claimed invention.
The inventor or a joint inventor is not in possession of the claimed method, because the inventor or joint inventor is not in possession of a generically recited histone deacetylase inhibitor (HDACi).
The recited genus of histone deacetylase inhibitors (HDACi) is defined solely by the function of the molecules encompassed by the genus, without imposing any limitations on the structure of the molecules. A person skilled in the art would be aware that molecules capable of inhibiting the activity of any a number of known histone deacetylases may have a broad variety of chemical structures.
The specification discloses a single HDAC inhibitor, a compound known as tucidinostat or chidamide or HBI-8000, represented by the chemical formula at page 2.
"The written description requirement [...] ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in the biological arts." Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352-53 (Fed. Cir. 2010) (en banc). Thus, a "sufficient description of a genus [...] requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350 (quoting Regents' of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69 (Fed. Cir. 1997)). Accordingly, "merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id. [F]unctionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).
In the present case, the specification discloses neither a representative number of species falling within the scope of the genus nor any structural features common to the members of the genus of HDAC inhibitor. Neither is there a disclosed or known correlation between the structure of a molecule and a function of inhibiting a histone deacetylase. Accordingly, the present specification fails to meet the written description requirement of 35 U.S.C. 112(a).
9. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
10. Claims 1-19 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Woody J. (US 20190216818).
Woody teaches a method of treating a subject with an HDAC inhibitor (HDACi) comprising administering an effective amount of HDAC inhibitor to the subject (e.g. claim 1). Since there is no manipulative difference between the method taught by Woody and the method recited instant claim 1, all outcomes of practicing Woody’s method are inherently the same as the outcomes of practicing the method of instant claim 1, including those recited in instant claim 1, and claims 2-7 dependent thereon. Accordingly, instant claims 1-7 are anticipated by Woody’s teachings.
More specifically, Woody teaches a method of treating cancer comprising administering an oral HDAC inhibitor in combination with a checkpoint inhibitor, in particular anti-PD-1 antibody nivolumab (e.g. claims 1, 2, 12-17, and 26). The oral HDAC inhibitor is administered at a dose of less than 80 mg per day, or less than 40 mg per day (e.g. claims 3-4). In a particular embodiment, the HDAC inhibitor is chidamide (tucidinostat) administered at a dose of 40 mg/day. The types of cancer treated by the method include leukemia, melanoma, renal cell cancer, and non-small cell lung cancer (e.g. claim 33 and [0102]). Accordingly, instant claims 8-19 are anticipated by Woody’s teachings.
In particular, claims 14-16 and 18 are included in the rejection, because “the cycle,” as recited, reads on daily administration for an indefinite period (claims 14-15) or up to ten weeks (claim 16). For this reason, the recitation of “day 2 of the cycle” in claim 18 reads on almost any administration schedule.
11. Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Bissonnette et al. (US 20180355042).
Bissonnette teaches a method for treating melanoma in a subject, comprising administering to said subject a therapeutically effective amount of a compound of the following formula:
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in combination with nivolumab (e.g. claim 22).
The above formula is the same as disclosed at page 6 of the present specification, representing a HDAC inhibitor referred to as tucidinostat or chidamide in the present application, and as HBI-8000 or chidamide by Bissonnette.
Since there is no manipulative difference between the method taught by Bissonnette and the method recited instant claim 1, all outcomes of practicing Bissonnette’s method are inherently the same as the outcomes of practicing the method of instant claim 1, including those recited in instant claim 1, and claims 2-7 dependent thereon. Accordingly, instant claims 1-11 are anticipated by Bissonnette’s teachings.
Bissonnette teaches embodiments wherein HBI-8000 is administered at a dose of 20 mg, 30 mg or 40 mg QD (i.e. once daily) (e.g. [0227]), and specifies that nivolumab is administered at an amount of about 240 mg once every two weeks (e.g. claim 27).
Claims 14-16 and 18 are included in the rejection for the same reasons as presented in section 10 above.
12. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
13. Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of each of U.S. Patents No. 10385131, 11535670, 10385130, 10287353, and 12122833.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of each of the patents, which recite methods of treating cancer comprising administering HDAC inhibitor tucidinostat/chidamide/HBI-8000 in combination with a PD-1/PD-L1 inhibitor (claim 1 of each of the five patents listed above). The limitations of instant claims 1-11 are inherent in the recited methods for the same reasons as presented in section 10 above.
14. Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the following copending applications:
USSN US PG Pub. No.
17/410459 20220110924
16/894532 20200383961
17/993567 20230151099
18/907983 20250026832
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of each of the above copending applications, which recite methods of treating cancer comprising administering HDAC inhibitor tucidinostat/chidamide/HBI-8000 in combination with a PD-1/PD-L1 inhibitor (claim 76 of USSN ‘459, claim 75 of US ‘532, claim 1 of US ‘567, and claim 1 of US ‘983). The limitations of instant claims 1-11 are inherent in the recited methods for the same reasons as presented in section 10 above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
15. The following prior art references, which teach various aspects of the claimed invention, are cited of record but not presently relied upon:
Chen et al. (US Pat. Pub. No. 20210069163) Anticancer Combination of Chidamide and Celecoxib Salts.
Gao et al. (2020) Anti-PD-1 Antibody (Sintilimab) Plus Histone Deacetylase Inhibitor (Chidamide) for the Treatment of Refractory or Relapsed Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (r/r-ENKTL): Preliminary Results from a Prospective, Multicenter, Single-Arm, Phase Ib/II Trial (SCENT). Blood 136 (Supplement 1): 39 (5 pages).
Clinical trial NCT02718066: Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer. Retrieved from https://clinicaltrials.gov/study/NCT02718066 on 06/10/2026; first posted on 03/24/2016; 13 pages.
16. Conclusion: no claim is allowed.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
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