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 .
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17-18 are 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.
The recitation “under conditions that allow for…host defense peptide” renders claims reading upon said recitation indefinite as the metes and bounds of the conditions applicant intends to be part of claimed invention are not clearly set forth. In the absence of any guidance from the speciation regarding conditions required, one of ordinary skill in the art would not have been apprised of the metes and bounds of the invention. For the purposes of applying art, the examiner interprets the recitation to include any step comprising contacting at least one cell with the composition of claim 1.
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.
(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.
Claim(s) 1-4 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Han et al. US 2015/0322405 A1 (Han).
Claims 1-4 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Han provides a method of producing a multipotent stem cell, said method comprising culturing at least one fibroblast cell in the presence of an effective amount of at least one small molecule reprogramming factor(s) that induces the cell to de-differentiate into a multipotent stem cell, wherein the method excludes the use of reprogramming factor(s) that are not small molecules (Abstract). Han teaches a preferred culture composition, the composition comprises: PD325901; valproic acid: BIX01294; RG108; CHIR9901; vitamin C; and A83-01 [0140 – 0147].
Thus, Han teaches a composition comprising at least one histone deacetylase inhibitor (e.g., valproic acid), at least one DNA methyltransferase inhibitor (e.g., RG108), and at least one histone methyltransferase inhibitor (e.g., BIX01294). Han teaches all of the instantly claimed elements. Thus, claims 1-4 are anticipated.
Claim(s) 1-3 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ginder, Gordon D., Matthew J. Whitters, and Joyce K. Pohlman. "Activation of a chicken embryonic globin gene in adult erythroid cells by 5-azacytidine and sodium butyrate." Proceedings of the National Academy of Sciences 81.13 (1984): 3954-3958 (Ginder).
Claims 1-3 and 13 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Ginder teaches a composition comprising sodium butyrate and 5-azacytidine (page 3956; FIG. 2).
Thus, Ginder teaches a composition comprising at least one histone deacetylase inhibitor (e.g., sodium butyrate) and at least one DNA methyltransferase inhibitor (e.g., azacitidine). Ginder teaches all of the instantly claimed elements. Thus, claims 1-3 and 13 are anticipated.
Claim(s) 1-3 and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Selene, Insija Ilyas, et al. "Histone deacetylase inhibitors in myelodysplastic syndrome." Blood 132 (2018): 5528 (Selene).
Claims 1-3 and 16 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Selene teaches a composition comprising a combination of mocetinostat or vorinostat and azacytidine (Results).
Thus, Selene teaches a composition comprising at least one histone deacetylase inhibitor (e.g., vorinostat or mocetinostat) and at least one DNA methyltransferase inhibitor (e.g., azacytidine). Selene teaches all of the instantly claimed elements. Thus, claims 1-3 and 16 are anticipated.
Claim(s) 1-2, 4, and 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by El Baba, Ranim, and Georges Herbein. "Management of epigenomic networks entailed in coronavirus infections and COVID-19." Clinical Epigenetics 12.1 (2020): 118 (Baba).
Claims 1-2, 4, and 14 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Baba teaches a composition comprising vorinostat and BIX-01294 (Table 1; page 6 of 12, left column).
Thus, Baba teaches a composition comprising at least one histone deacetylase inhibitor (e.g., vorinostat) and at least one histone methyltransferase inhibitor (e.g., BIX01294). Baba teaches all of the instantly claimed elements. Thus, claims 1-2, 4, and 14 are anticipated.
Claim(s) 1-2, 4, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mali, Prashant, et al. "Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes." Stem cells 28.4 (2010): 713-720 (Mali).
Claims 1-2, 4, and 12 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Mali teaches a composition comprising sodium butyrate and BIX01294 (Figure 2).
Thus, Mali teaches a composition comprising at least one histone deacetylase inhibitor (e.g., sodium butyrate) and at least one histone methyltransferase inhibitor (e.g., BIX01294). Mali teaches all of the instantly claimed elements. Thus, claims 1-2, 4, and 12 are anticipated.
Claim(s) 1, 3, and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Meng, Fanliang, et al. "Inhibition of DNA methyltransferases, histone deacetylases and lysine-specific demethylase-1 suppresses the tumorigenicity of the ovarian cancer ascites cell line SKOV3." International journal of oncology 43.2 (2013): 495-502 (Meng).
Claims 1, 3, and 5 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
The goal of Meng was to investigate whether the combination of trichostatin A (TSA) and 5-aza-2'-deoxycytidine (decitabine) was superior to single agent on tumorigenicity of ovarian cancer cells (Abstract). Meng found that tumorigenicity and metastasis of SKOV3 cells were significantly suppressed by the combination of TSA and decitabine in xenograft mouse models. Meng teaches that TSA is a potent histone deacetylase inhibitor with antitumor effect in a mouse model of breast cancer through promotion of histone acetylation which is the basis for anti-neoplastic activity (page 496). Decitabine, a cytosine analog is used in combination or sequentially with conventional chemotherapeutic agents is able to resensitize chemoresistant ovarian cancer cell lines to platinum or taxane. Meng discloses that SKOV3 (1x107) cells were mixed with TSA (0.1 mg/kg) and decitabine (5 mg/kg) and then injected into 4-5-week C3H.C-Prkdc/SCID mice intraperitoneally for total treatment of 5 days (page 497). Based on the results, suppression of tumorigenicity in vivo and the inhibitory effect on migration and invasion in vitro, Meng hypothesized that the combination of TSA and decitabine could also affect the implantation of cancer cells in vivo (page 501).
Thus, Meng teaches a composition comprising at least one histone deacetylase inhibitor (e.g., TSA) and at least one DNA methyltransferase inhibitor (e.g., decitabine). Meng teaches a method of treating cancer comprising intraperitoneally administering a composition comprising TSA and decitabine to mice. Intraperitoneal administration of the composition comprising TSA and decitabine inherently teaches a composition comprising a pharmaceutically acceptable carrier or excipient. Meng teaches all of the instantly claimed elements. Thus, claims 1, 3, and 5 are anticipated.
Claim(s) 17-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Meng, Fanliang, et al. "Inhibition of DNA methyltransferases, histone deacetylases and lysine-specific demethylase-1 suppresses the tumorigenicity of the ovarian cancer ascites cell line SKOV3." International journal of oncology 43.2 (2013): 495-502 (Meng) as applied to claims 1, 3, and 5 above.
Claims 17-18 are drawn to a method of inducing expression of at least one antimicrobial host defense peptide, the method comprising the step of: contacting at least one cell with the composition of claim 1 under conditions that allow for expression of the at least one antimicrobial host defense peptide.
Claim 19 is drawn to a method comprising the step of: administering to an animal the composition of claim 1.
Claim 20 is drawn to a method, comprising the step of: administering to an animal, either simultaneously or wholly or partially sequentially: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
As set forth supra, Meng teaches a method of treating cancer comprising intraperitoneally administering a composition comprising TSA and decitabine to mice.
Thus, Meng teaches a method of treating cancer comprising intraperitoneally administering a composition comprising TSA and decitabine to mice. Meng teaches all of the instantly claimed elements. Thus, claims 17-20 are anticipated.
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.
Claim(s) 1, 3, and 5-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dulski et al. US 6,068,987 (Dulski) and Joshi-Hangal et al. US 6,982,253 B2 (Joshi-Hangal) in combination.
Claims 1, 3, and 5-11 are drawn to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Dulski relates to histone deacetylase as a target for antiprotozoal agents (column 1, lines 66-67). Dulski teaches that parasitic protozoa are responsible for a wide variety of infections in man and animals (column 1, lines 7-10). Many of the diseases are life threatening to the host and cause considerable economic loss in animal husbandry. Dulski teaches a method for the treatment of protozoal infections comprising administering to a host suffering from a protozoal infection a therapeutically effective amount of a compound which inhibits histone deacetylase (column 4, lines 16-23). Dulski teaches that examples of known compounds which may histone deacetylase inhibitors and therefore useful in the treatment of protozoal diseases include Trichostatin A (column 4, lines 24-40).
Dulski teaches that histone deacetylase inhibitors may be administered to a host in need of treatment in a manner similar to that used for other antiprotozoal agents, for example, they may be administered parenterally, orally, topically, or rectally (column 7, lines 1-17). The dosage to be administered will vary according to the particular compound used, the infectious organism involved, the particular host, the severity of the disease, physical condition of the host, and the selected route of administration; the appropriate dosage can be readily determined by a person skilled in the art. For use as an anticoccidial agent, particularly in poultry, the compound is preferably administered in the animals feed or drinking water.
In preparing the compositions for oral dosage form, any of the usual pharmaceutical media may be employed (column 7, line 54 to column 8, line 3). For example, in the case of oral liquid preparations such as suspensions, elixirs and solutions, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like may be used; or in the case of oral solid preparations such as powders, capsules and tablets, carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be included.
Thus, Dulski teaches a composition for the treatment of a protozoal infection comprising a histone deacetylase inhibitor and a pharmaceutically acceptable carrier or excipient (e.g., water or oil). Dulski teaches that the composition may be formulated and administered as animal feed. Dulski teaches that the composition may further contain diluents and/or binders.
Dulski differs from the instantly claimed invention in that Dulski does not explicitly teach a composition comprising at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor; however, this deficiency would have been obvious in view of the teachings of Joshi-Hangal.
In the instant case, the references may be combined to show obviousness because Dulski and Joshi-Hangal are each drawn to a composition useful for treating a protozoal infection. They are from the same field of endeavor, and/or are reasonably pertinent to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
Joshi-Hangal relates to methods and compositions for preparing, formulating and administering decitabine to a host in need thereof (column 1, lines 7-10). The formulations of Joshi-Hangal may be delivered via various routes of administration (column 12, lines 50-60). They may be administered or co-administered orally, parenterally, topically, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery (for example by catheter or stent), subcutaneously, intraadiposally, intraarticularly, or intrathecally. Joshi-Hangal teaches that because glycerin can be readily mixed with water, the formulations can be easily and readily further diluted just prior to administration (column 13 lines 20-25). For example, the pharmaceutical formulations can be diluted with water 180, 60, 40, 30, 20, 10, 5, 2, 1 minute or less before administration to a patient. Joshi-Hangal teaches that the pharmaceutical formulations may be used to treat a variety of diseases including protozoan infections (column 18, line 35).
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious to combine decitabine with the composition of Dulski as histone deacetylase inhibitors and decitabine were recognized in the art as being useful for the treatment of protozoan infections. Use of materials in combination, each of which is known to function for intended purpose, is generally held to be prima facie obvious as the idea of combining them flows logically from their having been individually taught in the prior art. In the instant case, Dulski teaches a composition comprising a histone deacetylase inhibitor useful for treating protozoan infections. Joshi-Hangal teaches that decitabine is useful for treating protozoan infections. Thus, claims that require no more than the combination of two compounds or compositions useful for treating protozoan infections together in order to treat a protozoan infection in a subject set forth prima facie obvious subject matter.
All of the instant limitations are taught by the combination of Dulski and Joshi-Hangal. A person of ordinary skill in the art would have had a reason to combine the teachings of Dulski and Joshi-Hangal. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Dulski and Joshi-Hangal. Thus, claims 1, 3, and 5-11 would have been obvious based on the preponderance of the evidence.
Claim(s) 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dulski et al. US 6,068,987 (Dulski) and Joshi-Hangal et al. US 6,982,253 B2 (Joshi-Hangal) in combination as applied to claims 1, 3, and 5-11 above.
Dulski differs from the instantly claimed invention in that Dulski does not explicitly teach administering a composition further comprising at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor; however, this deficiency would have been obvious in view of the teachings of Joshi-Hangal for the reasons set forth above.
All of the instant limitations are taught by the combination of Dulski and Joshi-Hangal. A person of ordinary skill in the art would have had a reason to combine the teachings of Dulski and Joshi-Hangal. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Dulski and Joshi-Hangal. Thus, claims 17-20 would have been obvious based on the preponderance of the evidence.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over El Baba, Ranim, and Georges Herbein. "Management of epigenomic networks entailed in coronavirus infections and COVID-19." Clinical Epigenetics 12.1 (2020): 118 (Baba) as applied to claims 1-2, 4, and 14 above, and further in view of El‐Shimy, Ismail A., et al. "Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS‐CoV‐2 in the respiratory tract." Pharmacology Research & Perspectives 9.1 (2021): e00698 (El-Shimy).
Baba differs from the instantly claimed invention in that Baba does not explicitly teach a composition comprising mocetinostat and BIX01294; however, this deficiency would have been obvious in view of the teachings of El-Shimy.
In the instant case, the references may be combined to show obviousness because Baba and El-Shimy are each drawn to a composition comprising a HDAC inhibitor useful for treating COVID-19. They are from the same field of endeavor, and/or are reasonably pertinent to a composition comprising: (a) at least one histone deacetylase inhibitor; and (b) at least one methyltransferase inhibitor selected from a DNA methyltransferase inhibitor and/or a histone methyltransferase inhibitor.
El-Shimy teaches that vorinostat and mocetinostat are histone deacetylase (HDAC) inhibitors (page 4 of 13).
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious to substitute vorinostat with mocetinostat in the combination of Baba as they were both recognized in the art as being a HDAC inhibitor. The simple substitution of one known element (HDAC inhibitors) for another to obtain predictable results is prima facie obvious. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.
All of the instant limitations are taught by the combination of Baba and El-Shimy. A person of ordinary skill in the art would have had a reason to combine the teachings of Baba and El-Shimy. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Baba and El-Shimy. Thus, claim 15 would have been obvious based on the preponderance of the evidence.
Conclusion
Claims 1-20 are pending. Claims 1-20 are rejected. No claims are allowed.
Contacts
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex).
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/PATRICK T LEWIS/Primary Examiner, Art Unit 1691
/PL/
