DETAILED ACTION
Claims 13-16 and 18, submitted 31 March 2026, are pending in the application and subject to examination in the instant Office Action. Claim 17 has been cancelled by the Applicant.
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 .
Rejections – New and Modified
The status of the previously rejected claims in the Office Action mailed on 31 October 2025 are set out below.
Rejections under 35 U.S.C. §112(a)
The Applicant’s arguments are not sufficient to overcome the previous rejection for the reasons set out below.
Rejections under Non-statutory Double Patenting
The Applicant has opted to not file a Terminal Disclaimer until the current 112(a) rejections are remedied. Thus, the NSDP rejection is maintained.
Response to Arguments
Applicant's arguments filed 31 March 2026 have been fully considered but they are not persuasive.
The Applicant has argued that there is no requirement that the subject matter of the instantly claimed invention is described literally. While the Examiner agrees with this statement, there remains uncertainty in the claimed method of treating any tumor with a combination of any HDAC inhibitor and any PD1 inhibitor. Additionally, the Applicant contends that there may be situations where one species adequately supports a genus, again, the Examiner agrees with this statement, however, MPEP 2163(II)(3)(ii) which states that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)”. Stated another way, claims which are directed to a functionally defined genus (i.e., HDAC inhibitors or PD1 inhibitors) which are not supported by the specification and only define one type of structurally similar compounds are not representative of the full scope of the genus.
In response to Applicant’s arguments only, the Examiner would like to cite a new reference specifically to point to the variety of structures found in HDAC inhibitors which would lead to uncertainty in the treatment of all tumors with all HDAC inhibitors. Raucci et al. ("Advancements in hydrazide-based HDAC inhibitors: a review of recent developments and therapeutic potential." Journal of Medicinal Chemistry 68.14 (2025): 14171-14194.) discloses “There are 18 HDAC isoforms, categorized into four main classes: I, II, III, and IV, each with specific biological functions and tissue distributions” (pg. 14171, Section “Introduction”, Left Col., 1st paragraph). Raucci also teaches Figure 1, shown below, which displays the variety of structures associated with HDAC inhibitors, specifically between the selectivity moiety of HDAC 1-3, HDAC6, HDAC8 and HDAC11. One having ordinary skill in the art would not expect a HDAC inhibitor that targets HDAC1-3 to be effective against HDAC6 because Raucci also states “Researchers have focused on developing inhibitors with specificity also for other isoforms. Specifically, based on the evidence that HDAC6, unlike HDAC1, lacks a large cavity beneath the zinc located in the enzyme’s active site” (pg. 14177, Section “Alkylated Hydrazides”, Left Col., 1st paragraph)
Figure 1 taught by Raucci
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(pg. 14173, Section “Alkylated Hydrazides”, Top of Page)
Thus, the Applicant claiming the treatment of all tumors, all HDAC inhibitors and all PD1 inhibitors, when Example 4 of the instant specification specifically states “in vivo experiments show promising results with a combination of the HDACi LBH589 and anti-PDL1 blockade” is not within the scope of the provided disclosure.
While the Applicant has mentioned the PD1 inhibitors in the specification, the provided examples do not teach the use of the PD1 inhibitors, generally, and instead only teaches the use of a PDL1 antibody.
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.
New - Claims 13-16 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of a tumor wherein the tumor is melanoma, renal cancer and non-small cell lung cancer, does not reasonably provide enablement for all tumors. 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.
Breadth of the Claims
Instant claim 1 recites “A method for treating a tumor in a subject…”. Claim 1 is not drawn to any tumor in particular and thus can be interpreted to encompass all tumors.
Additionally, the term “treating” is defined to include the meaning “cure” and “prevent a disease, pathological condition or disorder”, for which the specification does not provide enablement for. It’s known in the art that there are many tumors which cannot be prevented.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to
treating a tumor with the combination of a HDAC inhibitor and a PD1 inhibitor.
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the
time the application was filed, about the subject matter to which the claimed invention
pertains. The relative skill of those in the art refers to the skill of those in the art at the
time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc.
v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir.
2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enablement requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
The prior art teaches the use of HDAC6 inhibitors in the treatment of some cancers. Huang et al. ("Small molecules targeting HDAC6 for cancer treatment: Current progress and novel strategies." Biomedicine & Pharmacotherapy 178 (2024): 117218.) teaches “The HDAC family comprises eighteen members that are phylogenetically classified into four classes based on their homology with yeast proteins: Class I (HDAC1, 2, 3 and 8), Class IIa (HDAC4, 5, 7 and 9), Class IIb (HDAC6 and10)and Class IV (HDAC11),which are all enzymes that depend on Zn 2+, while Class III HDACs (sirtuins 1–7) are enzymes that depend on NAD+. HDAC6, the largest member of the HDAC family, is categorized as a class IIb enzyme and is predominantly localized to the cytoplasmic compartment.” (pg. 1, Section “HDAC and HDAC6”, Right Col., 2nd paragraph). Huang also teaches that HDAC6 inhibitor can improve the effectiveness of other cancer therapies (pg. 2, Section “HDAC6 and Cancer”, Right Col., 3rd paragraph). Finally, Huang teaches support for the instant application by teaching “To date, several groups have confirmed that combination therapy consisting of selective HDAC6is and PD-1/PD-L1 antibody/inhibitor results in significantly improved effects on tumor growth compared to single-arm therapy strategy, highlighting the immunomodulatory capability of selective HDAC6is” (pg. 3, Section “HDAC6 and Immunity”, Right Col., 2nd paragraph).
Currently, there is unpredictability within the claimed invention with regards to the curing or the prevention of all tumors as there is no prior art that teaches that all tumors can be prevented with an HDAC inhibitor in combination with a PD1 inhibitor.
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known
the relevant art at the relevant time. Factors that may be considered in determining the
level of ordinary skill in the art may include: (A) “type of problems encountered in the
art;” (B) “prior art solutions to those problems;” (C) “rapidity with which innovations are
made;” (D) “sophistication of the technology; and” I “educational level of active workers
in the field. In a given case, every factor may not be present, and one or more factors
may predominate.” In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir.
1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1
USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co.,
713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of
ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art
with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely
related to the amount of knowledge in the state of the art as well as the predictability of
the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount
of guidance or direction” refers to that information in the application, as originally filed,
that teaches exactly how to make or use the invention. The more that is known in the
prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the
invention and the art in unpredictable, the specification would need more detail as to
how to make and use the invention in order to be enabling. The scope of the required
enablement varies inversely with the degree of predictability involved, but even in
unpredictable art, a disclosure of every operable species is not required. A single
embodiment may provide broad enablement in cases involving predictable factors, such
as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ
122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA
1971). However, in applications directed to inventions in arts where the results are
unpredictable, the disclosure of a single species usually does not provide an adequate
basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA
1938). In cases involving unpredictable factors, such as most chemical reactions and
physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166
USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide
more objective evidence to support the enablement of the aforementioned claims to
contrast the unpredictability of the subject matter art.
Currently, there is unpredictability in the field of endeavor regarding the currently claimed method of treating all tumors with any combination of HDAC inhibitor and PD1 inhibitor. The unpredictability stems from there being no prior art or post art to suggest that all tumors can be cured or prevented with any combination of HDAC inhibitor and PD1 inhibitor.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of
the unpredictability of the art. Given the context and scope of the claims mentioned
above, the inventor failed to provide the necessary amount of direction for one skilled in
the art to adequately use the invention across all suggested utility in the broadly stated
disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant provided guidance for certain aspects of the invention, such as modulating PDL1 expression and activity using the HDAC6KD melanoma cells found in Example 1 on pages 20-24 of the specification, PDL1 expression regulation through STAT3 modulation using HDAC6KD melanoma cell lines found in Example 3 on pages 25-27 of the specification and finally, the Applicant teaches the combinatory treatment of the pan HDAC inhibitor, LBH589, and an anti-PDL1 antibody in Example 4 found on pages 27-28 of the specification.
Existence of Working Examples
The provided examples focused on the combinatory treatment of melanoma cell lines using a pan-HDAC inhibitor, LBH589, and an undisclosed PDL1 which is detailed in Example 4 and Figure 27. However, this treatment does not appear applicable in the treatment of all tumor types with the combination of any HDAC inhibitor and any PD1 inhibitor as there is no prior art or Applicant provided data to suggest otherwise.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the
predictability of the art, and the direction provided by the inventor. For one skilled in the
art to practice the invention as disclosed, the artisan trying to practice Applicant’s
claimed invention would be required to undertake unduly burdensome activities
including:
Experimentation to demonstrate treatment of all claimed tumors through administration of the HDAC inhibitor in combination with a PD1 inhibitor.
Experimentation to demonstrate curative or prophylactic treatment of tumors through administration of the HDAC inhibitor in combination with a PD1 inhibitor.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H 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.
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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