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 .
Priority
The instant application 18/483,225 filed on October 9, 2023 is a divisional of U.S. Patent Application No. 18/049,589 filed on October 25, 2022, which is a continuation of U.S. Patent Application No. 17/269,470 filed on February 18, 2021, which is a 371 of PCT/US2019/047288 filed on August 20, 2019, which claims priority to, and the benefits of U.S. Provisional Application No. 62/719,935 filed on August 20, 2018.
Status of Claims
Acknowledge is made of the receipt and entry of the amendment to the claims filed on October 7, 2025, wherein claims 1, 14-15, 21, 31, 36, 45, 49-51, 53 and 55 are amended; claims 2, 4-7, 9-11, 24-29, 40-44, 46-47, 52 and 54 are canceled; claims 57-64 are newly added; and claims 3, 8, 12-13, 16-20, 22-23, 30, 32-35, 37-39 and 48 are unchanged.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 8, 12-23, 30-39, 45, 48-51, 53, and 55-64 are pending and under examination.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/6/2025 and 11/11/2025 were filed after the mailing date of the Non-Final Office Action on July 9, 2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Terminal Disclaimer
The terminal disclaimer filed on October 7, 2025 disclaiming the terminal portion of any
patent granted on this application which would extend beyond the expiration date of U.S. Patent No.
12,090,145 has been reviewed and is accepted. The terminal disclaimer has been recorded.
The terminal disclaimer filed on October 7, 2025 disclaiming the terminal portion of any
patent granted on this application which would extend beyond the expiration date of any patent
granted on App No. 18/749,726 has been reviewed and is accepted. The terminal disclaimer has been
recorded.
Action Summary
Claims 1, 3-4, 8, 12-23, 30-41, 43-45, and 47-56 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 are withdrawn in view of the claim amendments.
Claims 1, 3-4, 8, 12-23, 30-41, 43-45, and 47-56 rejected on the basis that it contains an improper Markush grouping of alternatives are withdrawn in view of the claim amendments.
Claims 1, 3, 12, 31-33, 37, 39, and 49 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826; cited in the IDS filed on January 17, 2025), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018; cited in the IDS filed on January 17, 2025), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31; cited in the IDS filed on January 17, 2025) and Lind et al. (US 6,579,857 B1), as evidenced by Martin-Jurdo et al. (A.J.V.R., 2011. Vol. 72, 9: 1164-1170; cited in the Non-Final Office Action mailed on May 5, 2024) are withdrawn in view of the claim amendment.
Claims 1, 3, 8, 12, 31-33, 37-39, and 49 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 B1) as applied to claims 1, 3, 12, 31-33, 37-39, and 49 above, and further in view of Weg (US 2014/0057988 A1) are withdrawn in view of the claim amendment.
Claims 1, 3, 12-13, 31-33, 37-41, and 49 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 B1) as applied to claims 1, 3, 12, 31-33, 37-39, and 49 above, and further in view of Di et al. (“Chapter 41: Formulation” in: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510; cited in the IDS filed on January 17, 2025) are withdrawn in view of the claim amendment.
Claims 1, 3, 12-13, 31-33, 36-41, and 49 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31), Lind et al. (US 6,579,857 B1) and Di et al. (“Chapter 41: Formulation” in: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510) as applied to claims 1, 3, 12-13, 31-33, 37-41, and 49 above, and further in view of McCormack et al. (CMAJ., 2011. Vol. 183(1): 65-69) are withdrawn in view of the claim amendment.
Claims 1, 3-4, 12, 31-33, 37-39, 45, 49, and 51-53 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 B1) as applied to claims 1, 3, 12, 31-33, 37-39, and 49 above, and further in view of McCormack et al. (CMAJ., 2011. Vol. 183(1): 65-69) (newly applied as necessitate by amendments) are withdrawn in view of the claim amendment.
Claims 1, 3, 12, 31-35, 37-39, and 49 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 Bl) as applied to claims 1, 3, 12, 31-33, 37-
39, and 49 above, and further in view of Andrade (J Clin Psychiatry, 2017.78, 6: e674-e677; cited in the Non-Final Office Action mailed on December 13, 2023) are withdrawn in view of the claim amendment.
Claims 14-16, 18, 22-23, and 50 rejected under 35 U.S.C. 103 as being unpatentable over
Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al.
(Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin
Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 Bl), as evidenced by Martin-Jurdo et al.
(A.J.V.R., 2011. Vol. 72, 9: 1164-1170) are withdrawn in view of the claim amendment.
Claims 14-16, 18, 22-23, 30 and 50 rejected under 35 U.S.C. 103 as being unpatentable over
Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al.
(Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin
Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 B1) as applied to claims 14-16, 18, 22-23,
and 50 above, and further in view of Weg (US 2014/0057988 A1) are withdrawn in view of the claim amendment.
Claims 14-16, 18, 22-23, 43-44 and 50 rejected under 35 U.S.C. 103 as being unpatentable
over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al.
(Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin
Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 Bl) as applied to claims 14-16, 18, 22-23,
and 50 above, and further in view of Di et al. ("Chapter 41: Formulation" in: Drug-Like Properties:
Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA,
USA: Elsevier Science, 2016: 497-510) are withdrawn in view of the claim amendment.
Claims 14-16, 18, 21-23, 43-44 and 50 rejected under 35 U.S.C. 103 as being unpatentable
over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al.
(Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin
Pharm., 2016. Vol. 7(2): 27-31), Lind et al. (US 6,579,857 Bl) and Di et al. ("Chapter 41: Formulation" in:
Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd
ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510) as applied to claims 14-16, 18, 22-23, 43-44 and
50 above, and further in view of McCormack et al. (CMAJ., 2011. Vol. 183(1): 65-69) are withdrawn in view of the claim amendment.
Claims 14-16, 18, 22-23, 47-48, 50, and 54-56 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J
Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 Bl) as applied to claims 14-16, 18,
22-23, and 50 above, and further in view of McCormack et al. (CMAJ., 2011. Vol. 183(1): 65-69) are withdrawn in view of the claim amendment.
Claims 14-16, 18-20, 22-23, and 50 rejected under 35 U.S.C. 103 as being unpatentable over
Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816-826), in view of Kara et al.
(Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 Bl) as applied to claims 14-16, 18, 22-23,
and 50 above, and further in view of Andrade (J Clin Psychiatry, 2017.78, 6: e674-e677; cited in the NonFinal Office Action mailed on December 13, 2023) are withdrawn in view of the claim amendment.
Claims 14-18, 22-23, and 50 rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Lind et al. (US 6,579,857 B1) as applied to claims 14-16, 18, 22-23, and 50 above, and further in view of van Velzen et al. (Anesthesiology, 2014. Vol. 121(1): 4-5) are withdrawn in view of the claim amendment.
Claims 1, 3-4, 8, 12-23, 30-41, 43-45, and 47-56 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,090,145 B2 (reference patent) in view of Weg (US 2014/0057988 A1) and Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018) are withdrawn in light of the terminal disclaimer filed on October 7, 2025.
Claims 1, 3-4, 8, 12-23, 30-41, 43-45, and 47-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 and 22-29 of copending Application No. 18/749,726 in view of Lind et al. (US 6,579,857 B1), Weg (US 2014/0057988 A1), and Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018) are withdrawn in light of the terminal disclaimer filed on October 7, 2025.
Claim Interpretation
The claimed term “about” in claims 1, 4, 14, 45 and 47-48 are reasonably construed in light of page 6, line 6-9 of the specification as shown below:
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127
714
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, and the term “about” includes the broadest variation of +/- 20% of the value specified; therefore, the
claimed term when used in the context of “less than about”, the upper limit is calculated as the specified value plus 20% of that value. For example, the upper limit for the phrase “less than about 15 mg” in claims 1 and 14:
15
+
0.30
×
15
=
19.5
, is reasonably interpreted as less than 19.5 mg. Applying the same calculation to the phrase “less than about 10 mg” in claims 4 and 47,
10
+
0.30
×
10
=
13
, and said phrase is reasonably interpreted as less than 13 mg. In addition, the same calculation is applied to the phrase “less than about 5 mg” in claims 45 and 48,
5
+
0.30
×
5
=
6.5
and said phrase is reasonably interpreted as less than 6.5 mg.
Regarding claim 1, the recitation of “sufficient to treat or ameliorate a mood disorder in a human subject when administered in combination” indicated below:
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190
748
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, is reasonably construed to be an intended use of the rapid-acting antidepressant and the mTOR inhibitor, respectively. Since the claim is interpretated to be a product, the intended use of the ingredient(s) does not further limit the structural components of said ingredient(s); and therefore, if the prior art(s) meet the structural limitation of the claimed product, it is capable of performing the intended use. See MPEP 2111.02. In addition, the limitation of “
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607
693
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” is reasonably construed by the Examiner that only one of the limitation (A) or (B) needs to be met. To the extent that the limitation (A) applies to the claimed kit, both the limitation (A)(i) and (A)(ii) need to be met. Regarding the limitation of (A)(i), the limitation recites before and after the coordinating conjunction “or” is being interpreted such only one limitation needs to be met, for instance, “the therapeutically effective dose of the RAAD in a dosage form suitable for oral administration or intravenous administration to the human subject” or “instructions to formulate the therapeutically effective dose of the RAAD in a formulation suitable for intravenous administration to a human
subject”; and same interpretation applies to (A)(ii). To the extent that the limitation (B) applies to the claimed kit, only one of the limitation (B)(i) or (B)(ii) needs to be meet.
Regarding claim 14, the limitations of “sufficient to treat or ameliorate a mood disorder in a human subject when administered in combination” indicated below:
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80
636
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; and the limitation of “
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174
638
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” are drawn to the intended use of the RAAD and the mTOR inhibitor, respectively. Since the claim is interpretated to be a product, the intended use of the ingredient(s) does not further limit the structural components of said ingredient(s); and therefore, if the prior art(s) meet the structural limitation of the claimed product, it is capable of performing the intended use. See MPEP 2111.02. Same interpretation applies to the limitation of “for a human subject” recites in the phrase of of “at least one dose of from 0.15 mg/kg to 10 mg/kg of a rapid-acting antidepressant (RAAD) for a human subject”. If the prior art teaches a rapid-acting antidepressant at the claimed range, it is capable of performing the intended use. In addition, the limitation of “
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578
710
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” is reasonably construed by the Examiner that only one of the limitation (A) or (B) needs to be met. To the extent that the limitation (A) applies to the claimed kit, both the limitation (A)(i) and (A)(ii) need to be met. Regarding the limitation of (A)(i), the limitation recites before and after the coordinating conjunction “or” is being interpreted such only one limitation needs to be met, for instance, “the therapeutically effective dose of the RAAD in a dosage form suitable for oral administration or intravenous administration to the human subject” or “instructions to formulate the therapeutically effective dose of the RAAD in a formulation suitable for intravenous administration to a human
subject”; and same interpretation applies to (A)(ii). To the extent that the limitation (B) applies to the claimed kit, only one of the limitation (B)(i) or (B)(ii) needs to be meet.
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 1 and 63 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.
Regarding claims 1 and 63, the recitation of “a therapeutically effective dose of a rapid-acting antidepressant (RAAD) sufficient to treat or ameliorate…disorder in a human subject when administered in combination with a therapeutically effective dose of a mammalian target of rapamycin (mTOR) inhibitor, and a therapeutically effective dose of the mTOR inhibitor sufficient to treat or ameliorate the …disorder in the human subject when administered in combination with the therapeutically effective dose of the RAAD” renders the claim indefinite, because the limitation can be interpret in various ways. To the extent “a therapeutically effective dose of a rapid-acting antidepressant (RAAD)” is used to treat or ameliorate a mood disorder or major depressive disorder in a human subject, said therapeutically effective dose of RAAD has to be combined with a therapeutically effective dose of a mTOR inhibitor; and for that instance, the kit would comprise a therapeutically effective dose of a RAAD combined with a therapeutically effective dose of a mTOR inhibitor, and a therapeutically effective dose of a mTOR inhibitor. Then it is not clear what is being referred as ”the mTOR inhibitor” and “the therapeutically effective dose of the mTOR inhibitor”. Is applicant referring to the first mTOR inhibitor that is being administered in combination with the RAAD, or the second mTOR inhibitor recites after the administration? To the extent that “a therapeutically effective dose of a rapid-acting antidepressant (RAAD)” is used for a different purpose that is not to treat or ameliorate a mood disorder, the kit would comprise a therapeutically effective dose of a RAAD in addition to a therapeutically effective dose of a mTOR inhibitor. The lack of clarity renders the claim indefinite, because one would not be reasonably apprised of the scope of the invention.
In order to advance prosecution, the examiner is examining the claim to the extent that the kit comprises a therapeutically effective dose of a RAAD, and less than about 10 mg of a mTOR inhibitor selected from the group consisting of (i) rapamycin or a pharmaceutically acceptable salt, solvate, or tautomer thereof, and (ii) temsirolimus or a pharmaceutically acceptable salt, solvate, or tautomer thereof.
Claim Rejections - 35 USC § 103
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 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 non-obviousness.
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 1, 12-13, 31-35, 37-39, 45, 49, 53, 57 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Marks et al. (US 2008/0255029 A1) in view of Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017), as evidenced by Andrade (The Journal of Clinical Psychiatry, 2017. Vol. 78, 6: e674-e677; cited in the Non-Final Office Action mailed on December 13, 2023).
Marks et al. teaches a combination of an mTOR inhibitor with at least one second drug substance, e.g. for any use as indicated under 1.1 to 1.8, including a method for treating endocrine tumors and a method for treating endocrine tumor invasiveness or symptoms associated with such tumor growth (see e.g., [0041], [0045], [0064]); wherein the mTOR inhibitor is selected from, inter alia, rapamycin, 40-[3-hydroxy-2-(hydroxy-methyl)-2-methylpropanoate]-rapamycin (also known as temsirolimus), and/or compound A (see e.g., [0101]-[0112]; [0005]). Marks et al. further teaches the mTOR inhibitor may be used, e.g., in any method of 1.1 to 1.8 alone or in combination with one or more, at least one, second drug substance, in which 1.1 is drawn to a method for treating endocrine tumors (see e.g., [0041]; [0062]). Marks et al. further teaches endocrine tumors include endocrine or neuroendocrine tumor symptoms and pituitary tumor symptoms (see e.g., [0061]), wherein the endocrine or neuroendocrine tumor symptoms includes, inter alia, chest pain (see e.g., [0057]); and the pituitary tumor symptoms includes, inter alia, moodiness or depression, anxiousness (see e.g., [0059]). Marks et al. further teaches in the combination, an mTOR inhibitor, such as rapamycin or rapamycin derivative, may be administered as appropriate, e.g. in dosages which are known for mTOR inhibitors, by any administration route, e.g. orally or parenterally; e.g. everolimus may be administered, e.g. orally, in dosages from 0.1 mg up to 15 mg, in dosages more preferably from 0.5 mg to 10 mg, e.g. in the form of (dispersible) tablets; Rapamycin or e.g. temsirolimus may be administered parenterally in similar dosage ranges (see e.g., [0089]). Marks et al. teaches combinations include fixed combinations, in which an mTOR inhibitor and at least one second drug substance are in the same formulation; kits, in which an mTOR inhibitor and at least one second drug substance in separate formulations are provided in the same package, e.g. with instruction for co-administration; and free combinations in which an mTOR inhibitor and at least one second drug substance are packaged separately, but instruction for concomitant or sequential administration are given (see e.g., [0071]). Marks et al. further teaches a second drug substance according to the present invention may be administered by any conventional route, for example enterally, e.g. including oral administration; and parenterally; e.g., in form of capsules, (injectable) solutions (see e.g., [0091]); unit dosage form may contain, for example, from about 0.1 mg to about 1500 mg (see e.g., [0092]).
Marks et al. does not teach the rapid-acting antidepressant instantly claimed.
Grassi et al. teaches the use of psychotropic drugs, namely those with an antidepressant profile, is a mandatory part of an integrated treatment of psychiatric disorders among cancer patients (see e.g., abstract, background). Grassi et al. further teaches antidepressants have been shown to be effective in the treatment of both psychiatric (depressive spectrum, stress-related disorder and anxiety disorders) and non-psychiatric cancer-related symptoms (e.g., pain, hot flashes and fatigue) (see e.g., abstract, design; p. 101, right column, line 5-11). Grassi et al. further teaches psychostimulants and other drugs, including ketamine (N-methyl-D-aspartate receptor antagonist) and psilocybin, have been use to rapidly alleviate depression in cancer patients (see e.g., Table 1, class - “psychostimulants and other drugs”; p. 105, right column, line 16-30). Grassi et al. further teaches in setting of terminal disease, the rapid onset of action of psychostimulants/ketamine may be preferable (see e.g., p. 107, Table 2, “Factors to be considered when prescribing Ads in cancer” section).
Regarding claims 1, 31, 32-35, 37-38, 45, 53, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine a dosage of 0.5 mg-10 mg rapamycin or temsirolimus taught by Marks et al., with a dosage of a therapeutically effective amount of a psychostimulant taught by Grassi et al., such as ketamine or psilocybin, as the second drug substance in a kit to arrive at the claimed invention. Please note the psychostimulant taught by Grassi et al. has a rapid onset of action, and that is a rapid-acting antidepressant. One would have been motivated to do so, because each is taught by the prior art to be useful for treating cancer-related symptoms. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One would have been further motivated to do so, because Marks et al. teaches a mTOR inhibitor, including rapamycin and temsirolimus, can be used alone for treating endocrine tumors, and said mTOR inhibitor can also be combine with a second drug substance for treating endocrine tumor invasiveness or symptoms associated with such tumor growth; and Grassi et al. teaches a psychostimulant, including ketamine and psilocybin, can be used to treat cancer-related symptoms in cancer patients. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the combination of 0.5 mg-10 mg rapamycin or temsirolimus and a therapeutically effective amount of a psychostimulant of Grassi et al., such as ketamine or psilocybin, each in an appropriate formulation suitable for administration, such as oral or intravenous, in a kit would have reasonably expected to be useful for treating cancer-related symptoms or treating endocrine tumors in addition to treating cancer-related symptoms. Please note the ketamine taught by Grassi et al. is a NMDA receptor modulator, and a racemic mixture of the enantiomers (R)-ketamine and (S)-ketamine, as evidenced by Andrade; and that meets the limitations of claims 32-35.
Regarding the limitations of “wherein the kit further comprises instructions…” in claims 12 and 13, each of these limitations is drawn to the content of the printed matter that describes the administering step(s) of the RAAD and the mTOR inhibitor, respectively, in the kit instantly claimed. Since the claim is interpreted to be a product, said method step(s) recites in the printed matter does not appear to further limit the structural component of the kit instantly claimed. According to MPEP 2112.01, III, “[where] the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)”. In the present case, the kit of Marks et al. and Grassi et al. sets forth above meets the structural limitation of the kit instantly claimed. Given that a kit or a package is required by law for pharmaceutical preparations and applications, and the FDA Guideline for Industry gives specific instructions for packaging and distributing medication for intended use and instructions for customers, one of ordinary skill in the art would have recognized the need for providing the instructions for the caregiver as those are mandated by federal law to include such instructions; and that renders obvious the limitations instantly claimed. In alternatives, it would have been prima facie obvious to one of ordinary skill in the art the time the application was filed to further modify the kit of Marks et al. and Grassi et al. sets forth above to include instruction for administration, including sequential administration. One would have been motivated to do so, because Marks et al. teaches the kit can provides instruction for co-administration, concomitant or sequential administration. One would have reasonable expectation of success to arrive the claimed invention by further incorporating the instruction(s) for administering the mTOR inhibitor and the second drug substance, including sequential administration.
Regarding the limitation of “wherein the human subject has a history of non-response
to at least one prior antidepressant therapy” in claim 39, the limitation pertains to the intended use of the RAAD and the mTOR inhibitor. Since the claim is interpreted to be a product, the human subject recites in the claim does not create a structural difference to the claimed product; and therefore, the human subject is not limiting, and the kit of Marks et al. and Grassi et al. sets forth above meets the structural limitation of the kit instantly claimed.
Regarding the limitation of “wherein the mood disorder is…” in claims 49, 57 and 59, the limitation pertains to the intended use of the RAAD and the mTOR inhibitor. Since the claim is interpreted to be a product, the mood disorder recites in the claim does not create a structural difference to the product; and therefore, the mood disorder is not limiting, and the kit of Marks et al. and Weg et al. sets forth above meets the structural limitation of the kit instantly claimed.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 1, 3, 8, 12-13, 31-39, 45, 49, 51, 53, 57, 59, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Marks et al. (US 2008/0255029 A1) in view of Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017) as applied to claims 1, 12-13, 31-35, 37-39, 45, 49, 53, 57 and 59 above, and further in view of Weg et al. (US 6,248,789 B1).
The teachings of Marks et al. and Grassi et al. are sets forth above and applied as before.
Marks et al. and Grassi et al. does not teach the therapeutically effective dose of the RAAD in claims 3, 36, 51 and 61. Marks et al. and Grassi et al. also does not teach an applicator in claim 8.
Weg et al. teaches oral administration of ketamine, a NMDA receptor antagonist (see e.g., Col. 1, line 60-61), for the treatment of pain from many causes, including but not limited to, inter alia, cancer (see e.g., Col. 5, line 3 to 14). Weg et al. further teaches the dose of ketamine is about 0.01 mg per kg of body weight (0.01 mg/kg) to about 1 mg/kg, preferably about 0.05 mg/kg to about 0.7 mg/kg (see e.g., Col.6 , line 36-39). Weg et al. further teaches in yet another embodiment, the dose ranges from about 1 mg to about 30 mg (see e.g., Col. 6, line 39-41). Weg et al. further teaches the term “ketamine,” as one of ordinary skill would presume, are isomers and enantiomers thereof that demonstrate analgesic properties, e.g., with greater potency or fewer side effects, or both (see e.g., Col. 7, line 22-25). Weg et al. further teaches in addition to the effects of ketamine alone administered via a transmucosal, transdermal, or oral route, which is particularly effective for breakthrough or spike pain conditions, the present invention is directed to administration of ketamine via any route, including parenteral administration in addition to transmucosal, transdermal, and oral administration parenteral administration (see e.g., p. 10, line 16-22). Weg et al. further teaches the advantages of transmucosal, transdermal, and oral administration for drug delivery are that they do not require injection using a syringe and needle (see e.g., Col. 7, line 39-41).
Regarding claims 3, 36, 51, and 61, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al. and Grassi et al. sets forth above by incorporating the second drug substance ketamine at the dose of about 0.01 mg/kg to about 1 mg/kg taught by Weg et al. One would have been motivated to do so, because Marks et al. teaches the second drug substance can be in an unit dosage from about 0.1 mg to about 1500 mg; and Weg et al. teaches the dose of ketamine ranges from about 1 mg to about 30 mg, and about 0.01 mg/kg to about 1 mg/kg for the treatment of pain caused by cancer. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the ketamine in the kit of Marks et al. and Grassi et al. at the therapeutically effective dose of 0.01 mg/kg to about 1 mg/kg taught by Weg et al. would successfully treat the cancer-related symptoms.
Regarding the limitation of “the kit further comprises an applicator” in claim 8, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the kit of Marks et al. and Grassi et al. sets forth above to further incorporate a syringe and needle taught by Weg et al. to arrive at the claimed invention. One would have been motivated to do so, because Marks et al. teaches the second drug substance can be in form of (injectable) solutions; and Weg et al. teaches the administration of ketamine can include any route, such as parenteral administration, and injection requires the use of a syringe and needle. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of a syringe and a needle as an applicator in the kit is essential for injection.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 14-16, 18, 21-23, 30, 48, 50, 55-56, 58, 60 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Marks et al. (US 2008/0255029 A1) in view of Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017) and Weg et al. (US 6,248,789 B1).
Marks et al. teaches a combination of an mTOR inhibitor with at least one second drug substance, e.g. for any use as indicated under 1.1 to 1.8, including a method for treating endocrine tumors and a method for treating endocrine tumor invasiveness or symptoms associated with such tumor growth (see e.g., [0041], [0045], [0064]); wherein the mTOR inhibitor is selected from, inter alia, rapamycin, 40-[3-hydroxy-2-(hydroxy-methyl)-2-methylpropanoate]-rapamycin (also known as temsirolimus), and/or compound A (see e.g., [0101]-[0112]; [0005]). Marks et al. further teaches the mTOR inhibitor may be used, e.g., in any method of 1.1 to 1.8 alone or in combination with one or more, at least one, second drug substance, in which 1.1 is drawn to a method for treating endocrine tumors (see e.g., [0041]; [0062]). Marks et al. further teaches endocrine tumors include endocrine or neuroendocrine tumor symptoms and pituitary tumor symptoms (see e.g., [0061]), wherein the endocrine or neuroendocrine tumor symptoms includes, inter alia, chest pain (see e.g., [0057]); and the pituitary tumor symptoms includes, inter alia, moodiness or depression, anxiousness (see e.g., [0059]). Marks et al. further teaches in the combination, an mTOR inhibitor, such as rapamycin or rapamycin derivative, may be administered as appropriate, e.g. in dosages which are known for mTOR inhibitors, by any administration route, e.g. orally or parenterally; e.g. everolimus may be administered, e.g. orally, in dosages from 0.1 mg up to 15 mg, in dosages more preferably from 0.5 mg to 10 mg, e.g. in the form of (dispersible) tablets; Rapamycin or e.g. temsirolimus may be administered parenterally in similar dosage ranges (see e.g., [0089]). Marks et al. teaches combinations include fixed combinations, in which an mTOR inhibitor and at least one second drug substance are in the same formulation; kits, in which an mTOR inhibitor and at least one second drug substance in separate formulations are provided in the same package, e.g. with instruction for co-administration; and free combinations in which an mTOR inhibitor and at least one second drug substance are packaged separately, but instruction for concomitant or sequential administration are given (see e.g., [0071]). Marks et al. further teaches a second drug substance according to the present invention may be administered by any conventional route, for example enterally, e.g. including oral administration; and parenterally; e.g., in form of capsules, (injectable) solutions (see e.g., [0091]); unit dosage form may contain, for example, from about 0.1 mg to about 1500 mg (see e.g., [0092]).
Marks et al. does not teach the rapid-acting antidepressant instantly claimed.
Grassi et al. teaches the use of psychotropic drugs, namely those with an antidepressant profile, is a mandatory part of an integrated treatment of psychiatric disorders among cancer patients (see e.g., abstract, background). Grassi et al. further teaches antidepressants have been shown to be effective in the treatment of both psychiatric (depressive spectrum, stress-related disorder and anxiety disorders) and non-psychiatric cancer-related symptoms (e.g., pain, hot flashes and fatigue) (see e.g., abstract, design; p. 101, right column, line 5-11). Grassi et al. further teaches psychostimulants and other drugs, including ketamine (N-methyl-D-aspartate receptor antagonist), have been use to rapidly alleviate depression in cancer patients (see e.g., Table 1, class - “psychostimulants and other drugs”; p. 105, right column, line 16-30). Grassi et al. further teaches in setting of terminal disease, the rapid onset of action of psychostimulants/ketamine may be preferable (see e.g., p. 107, Table 2, “Factors to be considered when prescribing Ads in cancer” section).
Weg et al. teaches oral administration of ketamine, a NMDA receptor antagonist (see e.g., Col. 1, line 60-61), for the treatment of pain from many causes, including but not limited to, inter alia, cancer (see e.g., Col. 5, line 3 to 14). Weg et al. further teaches the dose of ketamine is about 0.01 mg per kg of body weight (0.01 mg/kg) to about 1 mg/kg, preferably about 0.05 mg/kg to about 0.7 mg/kg (see e.g., Col.6 , line 36-39). Weg et al. further teaches in yet another embodiment, the dose ranges from about 1 mg to about 30 mg (see e.g., Col. 6, line 39-41). Weg et al. further teaches the term “ketamine,” as one of ordinary skill would presume, are isomers and enantiomers thereof that demonstrate analgesic properties, e.g., with greater potency or fewer side effects, or both (see e.g., Col. 7, line 22-25). Weg et al. further teaches in addition to the effects of ketamine alone administered via a transmucosal, transdermal, or oral route, which is particularly effective for breakthrough or spike pain conditions, the present invention is directed to administration of ketamine via any route, including parenteral administration such as intravenous injection (see e.g., p. 10, line 16-22 and 46-47).
Regarding claims 14, 16, 18, 21-23, 48, 55, 56 and 62, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine a dose of 0.5 mg-10 mg rapamycin or temsirolimus of Marks et al. with a dose of about 0.01 mg/kg to 1 mg/kg ketamine of Weg et al. as the second drug substance in the form of a kit to arrive at the claimed invention. Please note the ketamine taught by Weg et al. is a racemic ketamine. One would have been motivated to do so, because each is taught by the prior art to be useful for treating cancer-related symptoms. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One would have been further motivated to do so, because Marks et al. teaches 0.5 mg to 10 mg of an mTOR inhibitor, including temsirolimus, can be used alone for treating endocrine tumors, and said mTOR inhibitor can also be combined with a second drug substance in the same formulation administered by any conventional route, such as intravenous, for treating symptoms associated with such tumor growth; Grassi et al. teaches a psychostimulant, including ketamine, can be used to treat cancer-related symptoms in cancer patients; and Weg et al. teaches the dose of ketamine is 0.01 mg/kg to about 1 mg/kg ketamine for treating cancer-related pain, and said administration of ketamine can includes any route, including intravenous. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the combination of a dose of 0.5 mg-10 mg rapamycin or temsirolimus with a dose of 0.01 mg/kg to 1 mg/kg ketamine suitable for administration, such as intravenous, in a kit would reasonably expected to be useful for treating cancer-related symptoms or treating endocrine tumors in addition to treating cancer-related symptoms. Regarding the limitation of “wherein the RAAD is psilocybin…” in claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al., Grassi et al. and Weg et al. sets forth above by substituting the ketamine with psilocybin of Grassi et al. to arrive at the claimed invention. One would have been motivated to do so, because Grassi et al. teaches psychostimulants, including ketamine and psilocybin, are antidepressants with rapid onset of action useful for treating cancer-related symptoms. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the ketamine in the kit with psilocybin would have exerted the same or substantially similar effects as ketamine in treating cancer-related symptoms.
Regarding the limitation of “the kit further comprises an applicator” in claim 30, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al., Grassi et al. and Weg et al. sets forth above to further incorporate a syringe and needle taught by Weg et al. to arrive at the claimed invention. One would have been motivated to do so, because Marks et al. teaches the second drug substance can be in form of (injectable) solutions; and Weg et al. teaches the administration of ketamine can include any route, such as parenteral administration, and injection requires the use of a syringe and needle. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of a syringe and a needle as an applicator in the kit is essential for injection.
Regarding the limitation of “wherein the mood disorder is…” in claims 50, 58 and 60, the limitation pertains to the intended use of the RAAD and the mTOR inhibitor. Since the claim is interpreted to be a product, the mood disorder recites in the claim does not create a structural difference to the claimed product; and therefore, the mood disorder is not limiting, and the kit of Marks et al., North, Grassi et al. and Weg sets forth above meets the structural limitation of the kit instantly claimed.
Therefore, the claimed invention is prima facie obvious for one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 14-23, 30, 48, 50, 55-56, 58, 60 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Marks et al. (US 2008/0255029 A1) in view of Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017) and Weg et al. (US 6,248,789 B1) as applied to claims 14-16, 18, 21-23, 30, 48, 50, 55-56, 58, 60 and 62 above, and further in view of Rey (WO 2018/234568 A2).
The teachings of Marks et al., Grassi et al., and Weg et al. are sets forth above and applied as before.
Marks et al., Grassi et al., and Weg et al. does not teach the hydroxynorketamine as claimed in claim 17. Marks et al., Grassi et al., and Weg et al. does not teach the (R)-ketamine as claimed in claim 19. Marks et al., Grassi et al., and Weg et al. does not teach the (S)-ketamine in claim 20.
Rey teaches hydroxynorketamine for the use in the treatment of depression (see e.g., title; page 1, line 2-4). Rey further teaches the antidepressant effect of intraperitoneal administered (R,S)-ketamine
revealed that the metabolism of (R,S)-ketamine into (2S,6S;2R,6R)-hydroxynorketamine is essential for the antidepressant effect (see e.g., p. 1, line 32-35). Rey further teaches hydroxynorketamine is administered in form of at least one prodrug selected from, inter alia, (S)-Ketamine, (R)-Ketamine, (R,S)-Ketamine or pharmaceutically salts or solvates or mixtures thereof (see e.g., claims 1 and 4).
Regarding the limitation of “hydroxynorketamine” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al., Grassi et al. and Weg et al. sets forth above by substituting the ketamine with hydroxynorketamine of Rey to arrive at the claimed invention. One would have been motivated to do so, because Rey teaches hydroxynorketamine is a metabolite of (R,S)-ketamine essential for the antidepressant effect. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the ketamine in the kit with hydroxynorketamine would have exerted the same or substantially similar effects as ketamine in treating cancer-related symptoms.
Regarding the limitation of “(R)-Ketamine” in claim 19, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al., Grassi et al. and Weg et al. sets forth above by substituting the ketamine with (R)-ketamine of Rey to arrive at the claimed invention. One would have been motivated to do so, because Rey teaches the prodrug of hydroxynorketamine, including (R,S)-ketamine and (R)-ketamine, can be interchanged for treating depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the ketamine in the kit with (R)-ketamine would have exerted the same or substantially similar effects as ketamine in treating cancer-related symptoms.
Regarding the limitation of “(S)-Ketamine” in claim 20, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of Marks et al., Grassi et al. and Weg et al. sets forth above by substituting the ketamine with (S)-ketamine of Rey to arrive at the claimed invention. One would have been motivated to do so, because Rey teaches the prodrug of hydroxynorketamine, including (R,S)-ketamine and (S)-ketamine, can be interchanged for treating depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the ketamine in the kit with (S)-ketamine would have exerted the same or substantially similar effects as ketamine in treating cancer-related symptoms.
Therefore, the claimed invention is prima facie obvious for one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 63 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Marks et al. (US 2008/0255029 A1) in view of Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017), and Weg et al. (US 6,248,789 B1).
Marks et al. teaches a combination of an mTOR inhibitor with at least one second drug substance, e.g. for any use as indicated under 1.1 to 1.8, including a method for treating endocrine tumors and a method for treating endocrine tumor invasiveness or symptoms associated with such tumor growth (see e.g., [0041], [0045], [0064]); wherein the mTOR inhibitor is selected from, inter alia, rapamycin, 40-[3-hydroxy-2-(hydroxy-methyl)-2-methylpropanoate]-rapamycin (also known as temsirolimus), and/or compound A (see e.g., [0101]-[0112]; [0005]). Marks et al. further teaches the mTOR inhibitor may be used, e.g., in any method of 1.1 to 1.8 alone or in combination with one or more, at least one, second drug substance, in which 1.1 is drawn to a method for treating endocrine tumors (see e.g., [0041]; [0062]). Marks et al. further teaches endocrine tumors include endocrine or neuroendocrine tumor symptoms and pituitary tumor symptoms (see e.g., [0061]), wherein the endocrine or neuroendocrine tumor symptoms includes, inter alia, chest pain (see e.g., [0057]); and the pituitary tumor symptoms includes, inter alia, moodiness or depression, anxiousness (see e.g., [0059]). Marks et al. further teaches in the combination, an mTOR inhibitor, such as rapamycin or rapamycin derivative, may be administered as appropriate, e.g. in dosages which are known for mTOR inhibitors, by any administration route, e.g. orally or parenterally; e.g. everolimus may be administered, e.g. orally, in dosages from 0.1 mg up to 15 mg, in dosages more preferably from 0.5 mg to 10 mg, e.g. in the form of (dispersible) tablets; Rapamycin or e.g. temsirolimus may be administered parenterally in similar dosage ranges (see e.g., [0089]). Marks et al. teaches combinations include fixed combinations, in which an mTOR inhibitor and at least one second drug substance are in the same formulation; kits, in which an mTOR inhibitor and at least one second drug substance in separate formulations are provided in the same package, e.g. with instruction for co-administration; and free combinations in which an mTOR inhibitor and at least one second drug substance are packaged separately, but instruction for concomitant or sequential administration are given (see e.g., [0071]). Marks et al. further teaches a second drug substance according to the present invention may be administered by any conventional route, for example enterally, e.g. including oral administration; and parenterally; e.g., in form of capsules, (injectable) solutions (see e.g., [0091]); unit dosage form may contain, for example, from about 0.1 mg to about 1500 mg (see e.g., [0092]).
Marks et al. does not teach the rapid-acting antidepressant, racemic ketamine, instantly claimed.
Grassi et al. teaches the use of psychotropic drugs, namely those with an antidepressant profile, is a mandatory part of an integrated treatment of psychiatric disorders among cancer patients (see e.g., abstract, background). Grassi et al. further teaches antidepressants have been shown to be effective in the treatment of both psychiatric (depressive spectrum, stress-related disorder and anxiety disorders) and non-psychiatric cancer-related symptoms (e.g., pain, hot flashes and fatigue) (see e.g., abstract, design; p. 101, right column, line 5-11). Grassi et al. further teaches psychostimulants and other drugs, including ketamine (N-methyl-D-aspartate receptor antagonist), have been use to rapidly alleviate depression in cancer patients (see e.g., Table 1, class - “psychostimulants and other drugs”; p. 105, right column, line 16-30). Grassi et al. further teaches in setting of terminal disease, the rapid onset of action of psychostimulants/ketamine may be preferable (see e.g., p. 107, Table 2, “Factors to be considered when prescribing Ads in cancer” section).
Weg et al. teaches oral administration of ketamine, a NMDA receptor antagonist (see e.g., Col. 1, line 60-61), for the treatment of pain from many causes, including but not limited to, inter alia, cancer (see e.g., Col. 5, line 3 to 14). Weg et al. further teaches the dose of ketamine is about 0.01 mg per kg of body weight (0.01 mg/kg) to about 1 mg/kg, preferably about 0.05 mg/kg to about 0.7 mg/kg (see e.g., Col.6 , line 36-39). Weg et al. further teaches in yet another embodiment, the dose ranges from about 1 mg to about 30 mg (see e.g., Col. 6, line 39-41). Weg et al. further teaches the term “ketamine,” as one of ordinary skill would presume, are isomers and enantiomers thereof that demonstrate analgesic properties, e.g., with greater potency or fewer side effects, or both (see e.g., Col. 7, line 22-25). Weg et al. further teaches in addition to the effects of ketamine alone administered via a transmucosal, transdermal, or oral route, which is particularly effective for breakthrough or spike pain conditions, the present invention is directed to administration of ketamine via any route, including parenteral administration such as intravenous injection (see e.g., p. 10, line 16-22 and 46-47).
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine 0.5 mg to 10 mg temsirolimus of Marks et al. with about 0.01 mg/kg to 1 mg/kg ketamine of Weg et al. as the second drug substance in the same formulation in the kit to arrive at the claimed invention. Please note the ketamine taught by Weg et al. is a racemic ketamine. One would have been motivated to do so, because each is taught by the prior art to be useful for treating cancer-related symptoms. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One would have been further motivated to do so, because Marks et al. teaches 0.5 mg to 10 mg of an mTOR inhibitor, including temsirolimus, can be used alone for treating endocrine tumors, and said mTOR inhibitor can also be combined with a second drug substance in the same formulation administered by any conventional route, such as intravenous, for treating symptoms associated with such tumor growth; Grassi et al. teaches a psychostimulant, including ketamine, can be used to treat cancer-related symptoms in cancer patients; and Weg et al. teaches the dose of ketamine is 0.01 mg/kg to about 1 mg/kg ketamine for treating cancer-related pain, and said administration of ketamine can includes any route, including intravenous. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the combination of 0.5 mg-10 mg temsirolimus with 0.01 mg/kg to 1 mg/kg ketamine in the same formulation suitable for intravenous administration in a kit would have reasonably expected to be similarly useful for treating cancer-related symptoms or treating endocrine tumors in addition to treating cancer-related symptoms.
Therefore, the claimed invention is prima facie obvious for one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant’s arguments filed on October 7, 2025 have been fully considered.
Given that applicant did not put forth any arguments against the previous rejection on the record, the rejection has been revisited and modified in light of the claim amendments for the reasons set forth herein.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claim 1, 3, 8, 12-23, 30-39, 45, 48-51, 53 and 55-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,793,794 B2, in view of Marks et al. (US 2008/0255029 A1), Weg (US 2014/0057988 A1; cited in the previous Office Action mailed on 7/9/2025), Grassi et al. (Ann Oncol, 2018. Vol. 29(1):101-111. Published online on October 9, 2017) and Rey (WO 2018/234568 A2).
The claims of the reference patent are drawn to a method of treating a mood disorder or a major depressive mood disorder in a human subject in need thereof, the method comprising: a) administering to the human subject a dose ranging from 0.15 mg/kg to 10 mg/kg of a rapid-acting antidepressant (RAAD) selected from the group consisting of ketamine, S-ketamine, R-ketamine, and combinations thereof; and b) administering to the subject a dose ranging from 0.5 mg to 40 mg of rapamycin; wherein the RAAD and the rapamycin are co-formulate or in separate formulation; wherein the RAAD or the rapamycin is administered to the human subject by oral or intravenously delivery; wherein the human subject has a history of non-response to at least one prior antidepressant.
The claims of the reference patent does not teach a kit. The claims of copending application does not teach the applicator in claims 8 and 30. The claims of the reference patent does not teach psilocybin in claims 15 and 31.
Marks et al. teaches a combination of an mTOR inhibitor with at least one second drug substance, e.g. for any use as indicated under 1.1 to 1.8, including a method for treating endocrine tumor invasiveness or symptoms associated with such tumor growth (see e.g., [0041], [0045], [0064]); wherein the mTOR inhibitor is selected from, inter alia, rapamycin and/or 40-[3-hydroxy-2-(hydroxy-methyl)-2-methylpropanoate]-rapamycin (also known as temsirolimus)(see e.g., [0101]-[0112]; [0005]). Marks et al. further teaches combinations can include fixed combinations, in which an mTOR inhibitor and at least one second drug substance are in the same formulation; kits, in which an mTOR inhibitor and at least one second drug substance in separate formulations are provided in the same package, e.g. with instruction for co-administration; and free combinations in which an mTOR inhibitor and at least one second drug substance are packaged separately, but instruction for concomitant or sequential administration are given (see e.g., [0071]). Marks et al. further teaches endocrine tumors include endocrine or neuroendocrine tumor symptoms and pituitary tumor symptoms (see e.g., [0061]), including, inter alia, moodiness or depression (see e.g., [0059]).
Weg teaches a unit dosage form and corresponding kit including the formulation and composition of the present invention disposed within separable containers within an administration device such as a syringe (see e.g., [0029]). Weg further teaches the composition comprising NMDA receptor antagonist ketamine and its pharmaceutically acceptable salt (see e.g., claims 2, 14, 16); wherein the NMDA receptor antagonist is administered intravenously (see e.g., claim 7).
Grassi et al. teaches psychostimulants and other drugs, including ketamine (N-methyl-D-aspartate receptor antagonist) and psilocybin, have been use to rapidly alleviate depression in cancer patients (see e.g., Table 1, class - “psychostimulants and other drugs”; p. 105, right column, line 16-30).
Rey teaches hydroxynorketamine for the use in the treatment of depression (see e.g., title; page 1, line 2-4). Rey further teaches the antidepressant effect of intraperitoneal administered (R,S)-ketamine revealed that the metabolism of (R,S)-ketamine into (2S,6S;2R,6R)-hydroxynorketamine is essential for the antidepressant effect (see e.g., p. 1, line 32-35).
The conflicting claims of the reference patent recites a method of treating whereas the rejected claim covers a product, in this case, a kit. It would have been prima facie obvious to one of ordinary skill in the art to modify the RAAD and the rapamycin taught in the method of the reference patent to package each of these therapeutic agent together as a kit as taught by Marks et al. One would have been motivated to do so, because Mark et al. teaches an mTOR inhibitor, including temsirolimus, and at least one second drug substance can be combined in a kit in the same package with instruction. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by packaging the RAAD and the rapamycin together in a kit would have permits administration of said therapeutic agent(s).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In the present case, the therapeutically effective dose of the NMDA receptor modulator and the therapeutically effective dose of the rapamycin taught by the reference patent overlap or lie inside the claimed ranges, and that renders obvious the limitations instantly claimed.
Regarding the limitation of “an applicator” in claims 8 and 30, it would have been prima facie obvious to a person of ordinary skill in the art at the time the application was filed to modify the kit of reference patent and Marks et al. as set forth above to further incorporate a syringe as the administration device taught by Weg et al. One would have been motivated to do so, because Weg teaches the kit including the composition comprising intravenous ketamine can dispose within a syringe as the administration device. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the incorporation of a syringe in the kit would successfully facilitate the delivery of intravenous ketamine, and that renders obvious the limitation instantly claimed.
Regarding the limitation of “temsirolimus” in claims 14, 21, 23, 36, 37, 63, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of reference patent and Marks et al. as set forth above by substituting the rapamycin with temsirolimus or Marks et al. One would have been motivated to do so, because Marks et al. teaches rapamycin and temsirolimus are both mTOR inhibitors that can be interchange to treat symptoms associated with such tumor growth, including moodiness or depression. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the substitution of rapamycin with temsirolimus in the kit would have exerted the same or substantially similar mTOR inhibiting effects as rapamycin.
Regarding the limitation of “psilocybin” in claims 15 and 31, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of reference patent and Marks et al. as set forth above by substituting the rapid-acting antidepressant with psilocybin of Grassi et al. One would have been motivated to do so, because Grassi et al. teaches ketamine and psilocybin both rapidly alleviate depression in cancer patients. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the substitution of ketamine with psilocybin in the kit would have exerted the same or substantially similar antidepressant effects as ketamine.
Regarding the limitation of “hydroxynorketamine,” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the kit of reference patent and Marks et al. as set forth above by substituting the rapid-acting antidepressant with psilocybin of Grassi et al. One would have been motivated to do so, because Rey teaches hydroxynorketamine is a metabolite of (R,S)-ketamine essential for the antidepressant effect. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by substituting the ketamine with hydroxynorketamine in the kit would have exerted the same or substantially similar antidepressant effects as ketamine.
Regarding the limitations of “wherein the kit further comprises instructions…” in claims 12 and 13, each of these limitations is drawn to the content of the printed matter that describes the administering step(s) of the RAAD and the mTOR inhibitor, respectively, in the kit instantly claimed. Since the claim is interpreted to be a product, said method step(s) recites in the printed matter does not appear to further limit the structural component of the kit instantly claimed. According to MPEP 2112.01, III, “[where] the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)”. In the present case, the kit of reference patent and Marks et al. sets forth above meets the structural limitation of the kit instantly claimed. Given that a kit or a package is required by law for pharmaceutical preparations and applications, and the FDA Guideline for Industry gives specific instructions for packaging and distributing medication for intended use and instructions for customers, one of ordinary skill in the art would have recognized the need for providing the instructions for the caregiver as those are mandated by federal law to include such instructions; and that renders obvious the limitations instantly claimed. In alternatives, it would have been prima facie obvious to one of ordinary skill in the art the time the application was filed to further modify the kit of reference patent and Marks et al. sets forth above to include instruction for administration, including sequential administration. One would have been motivated to do so, because Marks et al. teaches the kit can provides instruction for co-administration, concomitant or sequential administration. One would have reasonable expectation of success to arrive the claimed invention by further incorporating the instruction(s) for administering the mTOR inhibitor and the second drug substance, including sequential administration.
Regarding the limitation of “wherein the human subject has a history of non-response
to at least one prior antidepressant therapy” in claim 39, the limitation pertains to the intended use of the RAAD and the mTOR inhibitor. Since the claim is interpreted to be a product, the human subject recites in the claim does not create a structural difference to the claimed product; and therefore, the human subject is not limiting, and the kit of reference patent and Marks et al. sets forth above meets the structural limitation of the kit instantly claimed.
Regarding the limitation of “wherein the mood disorder is…” in claims 49-50 and 57-60, the limitation pertains to the intended use of the RAAD and the mTOR inhibitor. Since the claim is interpreted to be a product, the mood disorder recites in the claim does not create a structural difference to the product; and therefore, the mood disorder is not limiting, and the kit of reference patent and Marks et al. sets forth above meets the structural limitation of the kit instantly claimed.
This is a nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628