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 .
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/05/2026 has been entered.
Claims 1 and 10-13 are pending in the application as of the response filed 05/05/2026. Claims 2-9 are cancelled. Claims 1 and 10-13 are examined herein.
Applicants arguments are rendered moot in view of the new grounds of rejection presented in this Office action.
The nonstatutory double patenting rejections are maintained and updated to include some new rejections.
In view of the pending claims, the following objections and rejections are made.
Information Disclosure Statement Not Considered, References Listed in Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and MPEP § 609.04(a), subsection I. states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 13, Ln. 4; Pg. 33, Ln. 15 of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The view numbers of the drawings should be corrected in the specification as required by 37 CFR 1.84(u)(1). See the drawing objection below.
Drawings Objected To
The drawings are objected to for the following reasons:
37 CFR 1.84(u)(1) states “The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s) … View numbers must be preceded by the abbreviation "FIG."”. The examiner suggests that the drawings should be properly labeled with the abbreviation “FIG.”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as "amended." If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either "Replacement Sheet" or "New Sheet" pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 103 - New
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.
Claims 1 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over the Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) in view of Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Regarding instant claim 1, Chen teaches a method for treating a disease in a mammal, comprising the step of delivering to the mammal a therapeutically effective amount of a compound/pharmaceutical compositions disclosed by Chen (i.e., administering to the mammal), wherein the disease is cancer (Para. [0015; Claim 4; Claim 5; Claim 3). Chen teaches the cancer treated by the methods to include Non-Hodgkin's lymphoma (Para. [0074]). Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3).
PNG
media_image1.png
223
549
media_image1.png
Greyscale
The conjugate of Formula II of Chen corresponds to a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide (TMZ),
perillyl alcohol (POH), and linoleic acid, i.e., POH-TMZ-LA of the instant claims.
Chen do not teach treating a primary cutaneous lymphoma mycosis fungoides.
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Chen and Querfeld to have utilized the triple conjugate of Chen in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success. Chen teaches a method for treating a disease in a mammal, comprising the administering to the mammal a therapeutically effective amount of a triple conjugate, POH-TMZ-LA of the instant claims, wherein the disease is cancer, such as Non-Hodgkin's lymphoma. Querfeld teaches TMZ has moderate activity against advanced mycosis fungoides/Sezary syndrome, achieving a 27% overall response rate in a phase II trial.
Therefore, one of ordinary skill in the art would have been motivated to administer the triple conjugate of Chen, POH-TMZ-LA, in a method of treating a mammal with a primary cutaneous lymphoma mycosis fungoides, with a reasonable expectation of success in treating such a condition. The motivation being to improve clinical outcomes in the treatment of difficult to treat cutaneous T-cell lymphomas, such as mycosis fungoides (Querfeld, Pg. 5749, first column, inset box).
Regarding instant claims 10-11, the combined teachings of Chen and Querfeld render the method of instant claim 1, prima facie obvious. Chen teaches the composition may be administered in combination with radiation or chemotherapeutic agents (Para. [0070]). Therefore, the limitations of instant claims 10-11 are rendered prima facie obvious.
Regarding instant claim 12, the combined teachings of Chen and Querfeld render the method of instant claim 1, prima facie obvious. Chen teaches the composition may be administered by the intranasal, oral, … inhalation, intravenous, … subcutaneous, intramuscular, …routes (Para. [0077]; Claim 11). Therefore, the limitations of instant claim 12 are rendered prima facie obvious.
Regarding instant claim 13, the combined teachings of Chen and Querfeld render the method of instant claim 1, prima facie obvious. Chen teaches the mammal is preferably a human (Para. [0093]). Therefore, the limitations of instant claim 13 are rendered prima facie obvious.
Claims 1 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over the Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) in view of Silva-Hirschberg (Effect of NEO212, a novel perillyl alcohol-temozolomide conjugate, on mycosis fungoides and Sezary syndrome, May 2019, in the IDS).
Regarding instant claim 1, Chen teaches a method for treating a disease in a mammal, comprising the step of delivering to the mammal a therapeutically effective amount of a compound/pharmaceutical compositions disclosed by Chen (i.e., administering to the mammal), wherein the disease is cancer (Para. [0015; Claim 4; Claim 5; Claim 3). Chen teaches the cancer treated by the methods to include Non-Hodgkin's lymphoma (Para. [0074]). Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3).
PNG
media_image1.png
223
549
media_image1.png
Greyscale
The conjugate of Formula II of Chen corresponds to a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide (TMZ),
perillyl alcohol (POH), and linoleic acid, i.e., POH-TMZ-LA of the instant claims.
Chen do not teach treating a primary cutaneous lymphoma mycosis fungoides.
Silva-Hirschberg teaches the effect of NEO212, a novel perillyl alcohol temozolomide conjugate, on mycosis fungoides and Sezary syndrome (Abstract, second paragraph). Silva-Hirschberg teaches NEO212 has a strong cytotoxic effect over mycosis fungoides cell lines at very low doses (Abstract, fourth paragraph). Silva-Hirschberg teaches NEO212 as a promising drug alternative for the treatment of mycosis fungoides (Abstract, fifth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Chen and Silva-Hirschberg to have utilized the triple conjugate of Chen in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success. Chen teaches a method for treating a disease in a mammal, comprising the administering to the mammal a therapeutically effective amount of a triple conjugate, POH-TMZ-LA of the instant claims, wherein the disease is cancer, such as Non-Hodgkin's lymphoma. Silva-Hirschberg teaches a NEO212, a novel perillyl alcohol temozolomide conjugate (POH-TMZ) has a strong cytotoxic effect over mycosis fungoides cell lines at very low doses. Hirschberg teaches NEO212 as a promising drug alternative for the treatment of mycosis fungoides.
Therefore, one of ordinary skill in the art would have been motivated to administer the triple conjugate of Chen, POH-TMZ-LA, in a method of treating a mammal with a primary cutaneous lymphoma mycosis fungoides, with a reasonable expectation of success in treating such a condition. The motivation being to provide a suitable alternative to treat this difficult to treat subtype of primary cutaneous lymphoma (Silva-Hirschberg, Abstract, first paragraph).
Regarding instant claims 10-11, the combined teachings of Chen and Silva-Hirschberg render the method of instant claim 1, prima facie obvious. Chen teaches the composition may be administered in combination with radiation or chemotherapeutic agents (Para. [0070]). Therefore, the limitations of instant claims 10-11 are rendered prima facie obvious.
Regarding instant claim 12, the combined teachings of Chen and Silva-Hirschberg render the method of instant claim 1, prima facie obvious. Chen teaches the composition may be administered by the intranasal, oral, … inhalation, intravenous, … subcutaneous, intramuscular, …routes (Para. [0077]; Claim 11). Therefore, the limitations of instant claim 12 are rendered prima facie obvious.
Regarding instant claim 13, the combined teachings of Chen and Silva-Hirschberg render the method of instant claim 1, prima facie obvious. Chen teaches the mammal is preferably a human (Para. [0093]). Therefore, the limitations of instant claim 13 are rendered prima facie obvious.
Double Patenting – Maintained and updated
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 § 2146 et seq. 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.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of US Patent No 9,522,918 B2 in view of Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld) and Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a skin condition in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate; wherein the perillyl alcohol carbamate is a triple conjugate of temozolomide (TMZ), perillyl alcohol (POH) and linoleic acid.
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘918 patent are drawn to a method of treating melanoma in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of the compound according to claim 1, 2 or 3, wherein claim 3 teaches the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
PNG
media_image2.png
236
563
media_image2.png
Greyscale
The ’918 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides or the limitations of instant claims 10-13.
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the composition may be administered in combination with radiation or chemotherapeutic agents (Para. [0070]). Chen teaches the composition may be administered by the intranasal, oral, … inhalation, intravenous, … subcutaneous, intramuscular, …routes (Para. [0077]; Claim 11). Chen teaches the mammal is preferably a human (Para. [0093]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘918 patent, Querfeld and Chen to have utilized the triple conjugate, POH-TMZ-LA , in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-4 of the ‘918 patent are therefore not patentably distinct in view of Querfeld and Chen.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US Patent No 10,696,680 B2 in view of Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld) and Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a condition in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate; wherein the perillyl alcohol carbamate is a triple conjugate of temozolomide (TMZ), perillyl alcohol (POH) and linoleic acid.
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘680 patent are drawn to a method for treating a cancer in a mammal, comprising the step of administering to the mammal a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, wherein claim 9 teaches the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA (Formula II).
PNG
media_image2.png
236
563
media_image2.png
Greyscale
Claim 6 of the reference ‘680 patent teaches the routes of administration as in instant claim 12.
The ’680 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides or the limitations of instant claims 10-11 and 13.
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the composition may be administered in combination with radiation or chemotherapeutic agents (Para. [0070]). Chen teaches the mammal is preferably a human (Para. [0093]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘680 patent, Querfeld and Chen to have utilized the triple conjugate, POH-TMZ-LA , in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-9 of the ‘680 patent are therefore not patentably distinct in view of Querfeld and Chen.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 9-14 of US Patent No 8,916,545 B2 in view of Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) and Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a condition in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate.
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘545 patent are drawn to a method for treating a glioblastoma in a mammal, comprising the step of delivering to the mammal a therapeutically effective amount of the perillyl alcohol carbamate of claim 1, wherein the perillyl alcohol carbamate comprises perillyl alcohol conjugated with temozolomide (TMZ). Claims 3-6 and 10-14 of the reference ‘545 patent teaches the method of instant claims drawn to further administering radiation or a chemotherapeutic agent as in instant claims 10-11 and routes of administration as in instant claim 12.
The ’545 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides; wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA; wherein the mammal is a human.
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the mammal is preferably a human (Para. [0093]).
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘545 patent, Chen and Querfeld to have utilized a triple conjugate, POH-TMZ-LA, in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-6 and 9-14 of the ‘545 patent are therefore not patentably distinct in view of Chen and Querfeld.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of US Patent No 9,913,838 B2 in view of Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) and Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a condition in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol conjugated with temozolomide (TMZ).
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘838 patent are drawn to a method for treating a brain metastasis of breast cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound comprising perillyl alcohol (POH) conjugated with temozolomide (TMZ) . Claims 5-6 of the reference ‘838 patent teaches the method of instant claims drawn to further administering radiation or a chemotherapeutic agent as in instant claims 10-11, claims 3-4 of the reference ‘838 patent teaches routes of administration as in instant claim 12.
The ’838 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides; wherein the perillyl alcohol conjugate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA; wherein the mammal is a human.
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the mammal is preferably a human (Para. [0093]).
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘838 patent, Chen and Querfeld to have utilized a triple conjugate, POH-TMZ-LA, in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-7 of the reference ‘838 patent are therefore not patentably distinct in view of Chen and Querfeld.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of US Patent No 9,987,271 B2 in view of Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) and Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol conjugated with temozolomide (TMZ).
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘271 patent are drawn to a method for treating oral cavity cancer in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate comprises perillyl alcohol conjugated with temozolomide (TMZ). Claims 4-5 of the reference ‘271 patent teaches the method of instant claims drawn to further administering radiation or a chemotherapeutic agent as in instant claims 10-11, claims 7-8 of the reference ‘271 patent teaches routes of administration as in instant claim 12.
The ’271 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides; wherein the perillyl alcohol conjugate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA; wherein the mammal is a human.
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the mammal is preferably a human (Para. [0093]).
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘271 patent, Chen and Querfeld to have utilized a triple conjugate, POH-TMZ-LA, in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-11 of the reference ‘271 patent are therefore not patentably distinct in view of Chen and Querfeld.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of US Patent No 10,092,562 B2 in view of Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) and Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol conjugated with temozolomide (TMZ).
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘562 patent are drawn to a method for treating a tumor of the central nervous system in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate comprises perillyl alcohol conjugated with temozolomide (TMZ). Claims 6-7 of the reference ‘562 patent teaches the method of instant claims drawn to further administering radiation or a chemotherapeutic agent as in instant claims 10-11, claim 2 of the reference ‘562 patent teaches a route of administration as in instant claim 12.
The reference ’562 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides; wherein the perillyl alcohol conjugate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA; wherein the mammal is a human.
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the mammal is preferably a human (Para. [0093]).
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘562 patent, Chen and Querfeld to have utilized a triple conjugate, POH-TMZ-LA, in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-8 of the reference ‘562 patent are therefore not patentably distinct in view of Chen and Querfeld.
This is a nonstatutory double patenting rejection.
Claims 1 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of US Patent No 9,580,372 B2 in view of Chen et al. (US 2016/0237092 A1, 18 August 2016, hereinafter Chen, of previous record) and Querfeld et al. (Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sezary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins, 01 September 2011, hereinafter Querfeld).
Although the claims at issue are not identical, both sets of claims are drawn to a method of treating a cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol conjugated with temozolomide (TMZ).
The instant claims are drawn to a method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, wherein the perillyl alcohol carbamate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA.
The claims of the reference ‘372 patent are drawn to a method for treating a glioblastoma in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of a Perillyl alcohol carbamate using a nasal delivery device, wherein the perillyl alcohol carbamate comprises 3-methyl 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carbonyl-carbamic acid-4-isopropenyl cyclohex-1-enylmethylester (i.e., TMZ-POH). Claims 3-4 of the reference ‘372 patent teaches the method of instant claims drawn to further administering radiation or a chemotherapeutic agent as in instant claims 10-11, claims 1-2 of the reference ‘372 patent teaches a route of administration as in instant claim 12.
The reference ’372 patent does not teach treating a primary cutaneous lymphoma mycosis fungoides; wherein the perillyl alcohol conjugate is the triple conjugate of temozolomide, TMZ, perillyl alcohol, POH, and linoleic acid, POH-TMZ-LA; wherein the mammal is a human.
Chen teaches a pharmaceutical composition comprising perillyl alcohol conjugated with a therapeutic agent, and an acylated aliphatic tail (Para. [0008]). Chen teaches an exemplary conjugate of Formula II (Para. [0013]; Claim 3), i.e., the triple conjugate, POH-TMZ-LA. Chen teaches the mammal is preferably a human (Para. [0093]).
Querfeld teaches Temozolomide, in a phase II multicenter trial of patients with advanced stages of mycosis fungoides /Sezary syndrome (MF/SS), wherein 26 patients were given TMZ daily doses of 200 mg/m2 for 5 days, for a total dose of 1,000 mg/m2 every 28 days (one cycle) (Abstract; Pg. 5749, second column, last paragraph). Querfeld teaches the overall response rate was 27%, including two complete remissions (8%) and five partial remissions (19%) (Abstract; Pg. 5751, first column, continued paragraph). Querfeld teaches the median disease-free survival was 4 months, while the median overall survival was 24 months (Abstract; Pg. 5751, first column, continued paragraph; Figure 2). Querfeld concludes that TMZ has moderate activity in patients with advanced MF and suggests treatment with TMZ may improve clinical outcomes (Pg. 5753, second column, last paragraph; Pg. 5749, first column, inset box).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘372 patent, Chen and Querfeld to have utilized a triple conjugate, POH-TMZ-LA, in a method of treating a mammal afflicted with primary cutaneous lymphoma mycosis fungoides, to arrive at the method of the instant claims with a reasonable expectation of success (a similar rationale as used in the 103 rejection above applies here).
The instant claims 1 and 10-13 and claims 1-4 of the reference ‘372 patent are therefore not patentably distinct in view of Chen and Querfeld.
This is a nonstatutory double patenting rejection.
Conclusion
Claims 1 and 10-13 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PADMAJA S RAO whose telephone number is (571)272-9918. The examiner can normally be reached 9:00-5:30pm EDT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PADMAJA S RAO/Examiner, Art Unit 1627
Prosecution Insights