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 .
DETAILED ACTION
Claims 1-12 are pending in the present application file.
Election/Restrictions
Applicant’s election of Group I (claims 1-11; drawn to a method for preparing a compound of formula I) and a species of compound of formula I without traverse in the reply filed July 28, 2026 is acknowledged by the Examiner.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species is not allowable over the prior art as indicated in the rejection under 35 U.S.C 112(b) and 103.
As the Applicant’s elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1-11 have been examined to the extent that they embrace and are readable on the elected embodiment and the above identified nonelected species. Claims 1-11 have been found to be not allowable.
Claim 12 is withdrawn from consideration by the Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Priority
The following continuity data is acknowledged in the present application file:
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Claim Objections
Claims 1-2 are objected to because of the following informalities:
Claim 1, line 20, “R2 is selected from the group consisting of” should read “R2 is”;
Claim 2, last line, “andiodosobenzene diacetate” should read “and iodosobenzene diacetate”.
Appropriate correction is required.
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 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 includes the limitation where “Compound D and Compound E undergo reductive amination to produce Compound G”, see Step (2) on page 2 of claim 1. Compound E and Compound G comprise the variable R3 which is not defined in the present claims. As such, the scope of the compounds encompassed by the presently claimed methods is indefinite to one of ordinary skill in the art.
Claim 10 also contains the step of “Reacting compound G with an organic or inorganic acid to obtain compound H”, see Step (3) in lines 3-4 of claim 10. Compounds G and H also contain the variable R3 without further definition. Claims 2-9 and 11, which are dependent upon claims 1 and 10, respectively, do not clarify the indefinite subject matter and are similarly rejected.
Compound H recited in claim 10 also contains the variable B, which is not defined in claim 10.
Applicant can amend the claims to include a definition for R3 and B to overcome this aspect of the rejection.
The present claims recite preferred embodiments for many of the steps, compounds, conditions and agents within the claimed methods. See claims 1, 5-6 and 9-11 which contain recitations of preferred embodiments. The phrases render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. See MPEP § 2173.05(d). Applicant may amend the claims to remove each instance of a preferred or exemplary embodiment to overcome this aspect of the rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites the limitation wherein in step (1), the solvent is a halogenated hydrocarbon solvent. Parent claim 1 limits the solvent in step (1) to C1-C4 halogenated hydrocarbon solvent, which is smaller in scope to the solvents claimed in present claim 3. As such, claim 3 fails to properly further limit the subject matter of parent claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over US 10836743 B2 (Liu et al.; Publication Date: November 17, 2020), in view of US 2011/0237584 A1 (Amishiro et al.; Publication Date: September 29, 2011).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Liu discloses methods of preparing a compound of present formula (I).
Liu discloses where a compound of formula (I) comprises compound A1 which corresponds to a compound of present formula (I) where ring A is C6 aromatic ring (phenyl), R1 is -CH2-R, where R is C6 aryl (phenyl), and n is 0. See col 6 and col 49 of Liu.
Liu discloses reductive amination step where a Compound D and Compound E undergo reductive amination to produce Compound G as well as Compound of formula (I). See Scheme 1 col 37 and col 45. Compound II of Liu corresponds to a compound of present formula E and Compound (III) corresponds to a compound of present formula D.
Liu discloses where the reductive amination is carried out with a polar solvent, such as methanol, an acid, such as acetic acid, and a borohydride reducing agent (e.g., sodium cyanoborohydride). See present claims 7-8.
Liu discloses in Example 1 a preparation of a compound of formula (I) corresponds to Applicant’s elected species where 167 mg of trans-2-phenylcyclopropylamine (Compound E) and 300 mg of benzyl 4-fluoro-4-formylpiperidine-1-carboxylate (Compound D) were combined in the presence of 20 mL of anhydrous methanol, 72 μl of acetic acid, and 142 mg of sodium cyanoborohydride. See col 49. In this exemplary reaction, the molar ratio of the compound of formula D to the reducing agent is 1:1.9 and the molar ratio of the compound of formula D to the compound of formula E is 1:1.1 (see present claim 9).
Liu discloses compounds of the invention as LSD1 inhibitors useful in the treatment and prevention of malignant tumor diseases associated with lysine-specific demethylase 1 (LSD1) inhibitors, including, but not limited to, diseases such as cancer, leukemia, and the like. See col 108-115 for inhibitor activity assays as well as in vivo pharmacological data for compounds of the invention.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Liu does not disclose a preparation of a compound of present formula D comprising present step (1), such as benzyl 4-fluoro-4-formylpiperidine-1-carboxylate.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Amishiro discloses where 1-benzyloxy-4-fluoropiperidin-4-ylcarbaldehyde was obtained from 1-benzyloxy-4-fluoropiperidin-4-ylmethanol according to Step 4 of Reference Example 8-92. See para 1170 on page 151 for Step 4 of Reference Example 8-92 and para 1185 on page 153 for Step 4 of Reference Example 8-96.
Step 4 of Reference Example 8-92 teaches oxidation of 4-Fluorotetrahydro-2H-pyran-4-ylmethanol in dichloromethane using Dess-Martin periodinane as oxidizing agent. See present claims 2-4. In Reference Example 8-92, the alcohol compound (4-Fluorotetrahydro-2H-pyran-4-ylmethanol (500 mg, 3.73 mmol)) and oxidizing agent (Dess-Martin periodinane (1.96 g, 4.47 mmol)) are present in a molar ratio of 1:1.2. See present claims 5-6.
One of ordinary skill in the art seeking to prepare a compound of Liu such as a compound of present formula I or formula G, for the purposes of treating malignant tumor disease associated with methylase 1 (LSD1), would be motivated to prepare a compound of present formula D in order to carry out the disclosed reductive amination. In seeking to find a method of preparing the necessary reagent for the reductive amination, one of skill would look to Amishiro which discloses an efficient synthesis of the compound of present formula D from a compound of present formula C. There would be a reasonable expectation of success as Liu teaches benzyl 4-fluoro-4-formylpiperidine-1-carboxylate and trans-2-phenylcyclopropylamine (compounds of present formula D and E, respectively) as reagents in the amination to prepare a compound of formula I and Amishiro teaches a preparation of benzyl 4-fluoro-4-formylpiperidine-1-carboxylate in specific working examples.
Therefore, the present claims are prima facie obvious and are properly rejected.
Conclusion
Claims 1-11 are rejected.
Claim 12 is withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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