DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 16-24, drawn to a method for increasing antigen presentation in tumor cells in a subject in need thereof, and SEQ ID NO: 2 in the reply filed on 30 January 2026 is acknowledged. The search and examination has been extended to SEQ ID NO: 1. Claims 1 and 4-8 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 16-24 are pending and being examined on the merits.
Priority
The application is a 371 of PCT EP2021/070650 filed 07/23/2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP20382681.3, filed on 07/28/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed 09/05/2023 has been considered.
Specification
The use of the term Gibco, Cell Signaling, Biolegend, Applied Biosystems, Novus Biologicals, to name a few, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. A cursory review of the specification has revealed these trademarks or names. It would be remedial to check the specification for additional trademarks or names and amend all upon amendment.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claims 16-24 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.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The claims are directed to a method for increasing antigen presentation in tumor cells in a subject in need thereof, comprising administering a -composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator to the subject. The claim require the provision of “ nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator”. Therefore, the claims require the provision of a genus of nucleic acid molecules that code for nucleic acid or proteins capable of activating LCoR.
The specification teaches the term "LCoR activator" refers to activators of LCoR, LCoR2 or LCoRL gene expression or of the expression of a nucleic acid codifying for SEQ ID NO: 1 or SEQ ID NO: 3, which are the amino acid sequences of human LCoR and LCoRL, respectively. As used herein, the term "LCoR activator" also refers to agents that increase the amount of LCoR protein, of LCoR2 protein or of LCoRL protein, or the amount of a protein comprising SEQ ID NO: 1. As used herein, the term "LCoR activator" also refers to activators of the expression of a nucleic acid codifying for SEQ ID NO: 2, which is the sequence of the HTH domain of LCoR/LCoRL. As used herein, the term "LCoR activator" also refers to agents that increase the amount of a protein comprising SEQ ID NO: 2 [pg. 2, lines 24-32]. The specification teaches that doxorubicin is a LCoR activator; however, doxorubicin is not a molecule encoded by an activator [pg. 2, line 20].
Palijan (Palijanet et al. The Journal of biological chemistry Vol. 284, NO. 44, pp. 30264–30274, 2009) teaches that HDAC6 can function as a cofactor of LCoR [abstract]. Palijan also teaches that LCoR was identified as a protein that interacts with the estrogen receptor (ERα) ligand [abstract]. Fernandes (Fernandes et al. 2003. Molecular Cell, Vol. 11, 139–150) teach that LCoR activity depends on multiple interacting protein complexes and regulatory pathway rather than just a single defined activator [pg. 146, col. 2 – 147, col. 2].
Accordingly, in view of the limited amount of guidance provided by the specification and the art, one of ordinary skill in the art would conclude that Applicant was not in possession of all nucleic acid molecules that code for nucleic acid or proteins capable of activating LCoR across this broad genus.
Claims 16-24 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 a method of increasing antigen presentation in tumor cells and a method of treating breast cancer, colon cancer, or sarcoma comprising administering a composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR), does not reasonably provide enablement for a method of increasing antigen presentation in tumor cells and a method of treating ‘any’ cancer comprising administering a composition comprising a “any” nucleic acid coding for “any” ligand dependent nuclear receptor corepressor (LCoR) “activator”. 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.
Nature of the Invention
The claims are directed to a method for increasing antigen presentation in tumor cells and a method of treating breast cancer comprising administering a composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator. Claim 17 requires that the tumor cells are breast cancer cell. Claim 21 envisage the types of cancers. Enablement of the claims turns on whether one of ordinary skill in the art could treat all cancers using all LCoR activators or all nucleic acids encoding a LCoR activator without undue experimentation.
State of the Art
Palijan (Palijanet et al. The Journal of biological chemistry Vol. 284, NO. 44, pp. 30264–30274, 2009) teaches that HDAC6 can function as a cofactor of LCoR [abstract]. Palijan also teaches that LCoR was identified as a protein that interacts with the estrogen receptor (ERα) ligand [abstract]. Fernandes (Fernandes et al. 2003. Molecular Cell, Vol. 11, 139–150) teach that LCoR activity depends on multiple interacting protein complexes and regulatory pathway rather than just a single defined activator [pg. 146, col. 2 – 147, col. 2].
According to the Human Protein Atlas (LCOR Protein Expression Summary.” The Human Protein Atlas, Human Protein Atlas, accessed 18 Apr. 2026, https://www.proteinatlas.org/ENSG00000196233-LCOR), LCOR is classified as having “low cancer specificity” and is detected broadly across cancers, with prognostic significance primarily highlighted in kidney renal clear cell carcinoma rather than as a pan-cancer treatment target. This suggests that it is not a uniquely selective therapeutic target for most individual cancers.
Rios teaches a method of increasing anti-tumor activity and treating a colon carcmoma or sarcoma tumor in a subject, the method involving administering doxorubicin (i.e., a ligand dependent nuclear receptor corepressor (LCoR) activator; as taught by the specification at example 2) or a polyethylene glycol coated liposome encapsulated form of doxorubicin [0008; 0019].
Breadth of the claims
The claims of the instant specification recite “A method for increasing antigen presentation in tumor cells in a subject in need thereof, comprising administering a -composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator to the subject ” and “A method of treating cancer comprising administering a composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator to a subject in need thereof”. This recitation broadly encompass the use of all nucleic acid encoding LCoR activators and treating all forms of cancer.
Guidance of the Specification
The specification discloses that LCoR expression decreases breast cancer proliferation and represses human prostate cancer growth [pg. 1, para 2-3]. While the specification discloses the use of a LCoR activator for many cancer types [pg. 4], the specification only provides working examples of treating breast cancer cells with an LCoR expression cassette (see Examples). The specification does not disclose any other cancer cell type or cancers that could be treated with a “LCoR activator”. Furthermore, while the specification teaches that doxorubicin treatment in cancer cells increased LCoR expression [example 2], the specification does show that doxorubicin treatment leads to complete tumor regression. The specification only teach that an over expression of LCoR leads to complete tumor regression and increases antigen presentation in tumor cells, not an LCoR “activator”.
Experimentation Required
In order to practice the claimed invention, an immense amount of experimentation would be required. To practice the invention as broadly claimed, it would be necessary for one of ordinary skill in the art to systematically test the ability of every LCoR activator to inhibit tumor regression or tumor growth from all cancer types. However, such experimentation would be highly unpredictable in view of the prior art which teaches that LCOR is classified as having “low cancer specificity”. Accordingly, practicing the invention as broadly claimed would require a massive amount of highly unpredictable experimentation.
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an undue experimentation would be required to make and use the invention as claimed.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-18 and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Rios (WO 2016/075174 A1) in view of White (US 2007/0054353 A1) and Shalek (WO2019/232542).
Regrading claim 16, 18 and 20-22, Rios teaches a method of increasing anti-tumor activity and treating a tumor in a subject, the method involving administering doxorubicin (i.e., a ligand dependent nuclear receptor corepressor (LCoR) activator; as taught by the specification at example 2) or a polyethylene glycol coated liposome encapsulated form of doxorubicin and an immunomodulatory agent that is one or more of an anti-PD-1 antibody (i.e., an immune checkpoint inhibitor (ICI) that inhibits PD-1), anti-PD-L1 antibody ((i.e., an immune checkpoint inhibitor (ICI) that inhibits PD-L1), anti-CTLA-4 antibody (i.e., an immune checkpoint inhibitor (ICI) that inhibits CTLA-4) [0008].
Regrading claims 17 and 21, Rios teach that doxorubicin is a widely-used chemotherapeutic drug for patients with breast cancer [0094]. Rios teaches a method of increasing anti-tumor activity and treating a colon carcmoma or sarcoma tumor in a subject [0019].
Regarding claim 23, Rios teaches administration of ipilimumab, nivolumab, etc. [0015-0016].
Regarding claim 24, Rios teaches the pharmaceutical composition comprising doxorubicin or Doxil is suitable for administration prior to, simultaneously with, or following administration of the pharmaceutical composition comprising GITR ligand, OX40 fusion protein, anti-CTLA-4 antibody, anti-PD-1 antibody, an anti-PD-L1 antibody or antigen binding fragments thereof [00147].
Rios do not teach administering a composition comprising a nucleic acid coding for a ligand dependent nuclear receptor corepressor (LCoR) activator and where the LCoR activator is a nucleic acid comprising a codifying sequence for SEQ ID NO: 1. Rios do not teach where the administration is used in a method of increasing antigen presentation.
White teaches a novel class of transcriptional corepressor polypeptides having an amino acid sequence which comprises at least one LXXLL nuclear receptor interacting NR box motif wherein L is leucine and X is any amino acid residue, and which are operably interactable with a nuclear receptor to actively repress transcription of DNA, such as “LCoR corepressor” (ligand-dependent corepressor) [abstract; 0033]. White teaches SEQ ID NO: 2, the protein structure of LCoR [Fig. 1, 0035] which is 99.6% identical to the current application SEQ ID NO: 1, thereby comprising a codifying sequence for SEQ ID NO: 1.
Shalek teach that anti-CTLA4, anti-PD-LI and/or anti-PDL1 upregulates genes involved in antigen presentation, such as LCoR [0012, 0398, claim 9].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to substitute the LCoR activator of doxorubicin of Rios with SEQ ID NO: 2 LCoR of White and the mthod could be used in a method of increasing antigen presentation in breast cancer cells. One of ordinary skill would be motivated to make the substitution since the expression of either the doxorubicin or SEQ ID NO: 2 would increase LCoR in the cell, Rios method teaches administration of anti-CTLA4, anti-PD-LI and/or anti-PDL1 and Shalek teach that anti-CTLA4, anti-PD-LI and/or anti-PDL1 upregulates genes involved in antigen presentation, such as LCoR.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Rios (WO 2016/075174 A1) in view of Shalek (WO2019/232542) and White (US 2007/0054353 A1) as applied to claims 16 and 18 and further in view of Meet (Meet et al. Journal of Controlled Release 195 (2014) 72–85).
The teachings of Rios, Shalek, and White are discussed above as applied to claim 16 and 18 and similarly apply to claim 19.
Rios, Shalek, and White do not teach where the nucleic acid is comprised in exosomes. Rios does teach administration of a polyethylene glycol coated liposome encapsulated form of doxorubicin.
Meet teach that extracellular vesicles, such as exosomes, are able to efficiently deliver their parental cell-derived molecular cargo to recipient cells and has gained much interest for drug delivery purposes [pg. 73, col. 1, para 3].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to substitute the polyethylene glycol coated liposome encapsulated form of doxorubicin with an exosome form of doxorubicin. One of ordinary skill would be motivated to make the modification with an expectation of success since Meet teaches that exosomes have gained much interest as a drug delivery cargo.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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