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 present Application, filed June 22, 2023, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/CN2022/088466, filed April 22, 2022, which claims priority to Chinese Patent Application Nos. CN202210072358, CN202110926676, CN202110653169, and CN202110443582, filed January 21, 2022, August 12, 2021, June 11, 2021 and April 23, 2021, respectively.
Status of the Claims
In the amendment filed October 13, 2023, claim 21 is canceled and new claims 23-24 are added. Claims 2-18 and 20 are amended. Claims 1-20 and 22-24 are currently pending.
Information Disclosure Statement
The information disclosure statements (IDSs), two in total, submitted on October 13, 2023 and March 5, 2024 are acknowledged.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, and 8-11 are anticipated by Stachel:
Claims 1, 5, and 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by German Patent No. DE1190466 to Stachel (hereinafter, “Stachel”).
Claim 1 recites a compound of formula (I)
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where the variable moieties are as defined.
Stachel teaches a process for the preparation of piperazine derivatives having a general formula
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where R can be any of several moieties, such as aryl (claim 1). Several working examples of Stacher are within the scope of instant claim 1, such as example 4,1-[1,2,3,4-Tetrahydro-naphthyl-(2')]-4-(o-methoxyphenyl)-piperazine (note that in an obsolete nomenclature, Stachel puts prime symbols on the four saturation sites of the naphthyl group, but it is clear from the disclosure, including the line drawing of the general formula, that this Example is as named above and drawn below):
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This is a compound of instant formula (I), where ring A is phenyl, ring B is cyclohexyl, Ring C is piperazinyl, and ring D is phenyl; L1, L2, and L3 are each a bond; Ra, Rb, and Rc are each hydrogen; and R1 is methoxy.
With respect to claim 5, instant ring C in the compound of Stachel is piperazinyl, the first alternative of claim 5. With respect to claims 8-11, each Ra, Rb, Rc, and Rd, respectively in the compound of Stachel is hydrogen.
Claims 1-2, 5-12, 19-20, and 22-24 are anticipated by Brown:
Claims 1-2, 5-12, and 19-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 8,669,249 to Brown et al. (hereinafter, “Brown”).
Brown teaches compounds of a generic formula for use as Poly (ADP-ribose) Polymerase (PARP) inhibitors
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where the variable moieties are as defined (col. 15, line 39 through col. 17, line 38). Among a substantial number of specific, real examples, Brown teaches 6-((4-(4-Fluorophenyl)-5,6-dihydropyridin-1(2H)-yl)methyl)-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)one (compound 33; col. 71, line 47 through col. 71, line 2).
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Brown compound 33 is a compound of instant claim 1, where ring A is heterocyclo and Ra is oxo and methyl (alkyl); ring B is aryl and Rb is hydrogen; L1 is -(CH2)1-; ring C is heterocyclyl and Rc is hydrogen; L2 is a bond; ring D is aryl and Rd is hydrogen; and L3 is a bond and R1 is hydrogen.
Brown compound 33 is a compound of claim 2 [formula (III)]
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where M5 is -CR6R7-O- with R6 and R7 being methyl and H; M6 is CH and Rb is hydrogen; L1 is -(CH2)1-; M1 and M2 are N, Rc is hydrogen, n5 and n6 are each one, and the variable bond is single; L2 is -(CH2)1-; ring D is aryl (phenyl) and Rd is hydrogen; and L3 is a bond and R1 is hydrogen.
With respect to claim 5, depending from claim 1, ring C of compound 33 of Brown is piperazinyl, the first listed option in claim 5. With respect to claim 6, ring D of compound 33 of Brown is phenyl, a C6-10 aryl. With respect to claim 7, R1 of compound 33 of Brown is hydrogen. While this claim specifies alternatives for different variable groups when present (e.g. R11, R22, R33, R44, R55, and R66, the claim does not require them to be present. With respect to claim 8, instant Ra of compound 33 of Brown is oxo and methyl (alkyl). With respect to claim 9, instant Rb of compound 33 of Brown is hydrogen. With respect to claim 10, instant Rc of compound 33 of Brown is hydrogen. With respect to claim 11, instant Rd of compound 33 of Brown is hydrogen.
Claim 12 recites a compound of formula (VII)
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which is highly similar to formula (III) of claim 2, except that ring D is required to be aryl or heteroaryl and L3 is required to be carbonyl. As such, compound 33 of Brown is nearly a compound of claim 12, except that it lacks the required carbon at M1 and carbonyl moiety at L3. However, Brown further teaches compounds, such as methyl 4-(1-((2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)methyl)piperidin-4-yl)benzoate (compound 207; col. 144, lines 35-58)
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that are within the scope of claim 12. Compound 207 of Brown is identical to compound 33 except that ring C is piperidinyl rather than piperazinyl and it includes a methyl formate group at the para position of the ring D. As such, compound 207 is a compound of instant claim 12, where M5 is -CR6R7-O- with R6 and R7 being methyl and H; M6 is CH and Rb is hydrogen; L1 is -(CH2)1-; M1 is CH and M2 is N, Rc is hydrogen, n5 and n6 are each one, and the variable bond is single; L2 is -(CH2)1-; M3 and M4 are CH and Rd is hydrogen; and R1 is methoxy (C1-6 alkoxy).
With respect to claim 19, Brown discloses a reductive amination involving 1-phenylpiperazine to prepare compound 33 (col. 71, lines 38-39). Phenylpiperazine is a compound of instant claim 19, where M1 and M2 are N, n5 and n6 are each one, Rc is hydrogen, L2 is a bond, ring D is phenyl and Rd is hydrogen, L3 is a bond, and R1 is hydrogen.
With respect to claim 20, Brown teaches compositions (pharmaceutical compositions) comprising a disclosed PARP inhibitor and a pharmaceutical excipient (col. 34, line 66 through col. 35, line 4). With respect to claims 22-23, Brown teaches a method of treating a disease state for which PARP possesses activity that contributes to the symptomology or pathology of the disease state, the method comprising administering a disclosed PARP inhibitor to a subject (col. 30, lines 31-39). Brown further teaches that the disease state can be cancer, such as breast cancer (col. 30, lines 39-60). With respect to claim 24, in compound 207 of Brown, each of R2-R9 is either hydrogen (R4, R5, R6) or methyl (R7) or absent (R8, R9).
Claims 1-11, 18-20, and 22-24 are anticipated by Packer:
Claims 1-11, 18-20, and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by International Patent Application No. WO2021/013735 to Packer et al. (hereinafter, “Packer”).
Packer discloses PARP inhibitors of a Formula (I)
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where the variable groups are as defined (pg. 2, lines 13-25). In a working example, Packer teaches 5-[4-[(7-ethyl-6-oxo-5H-1.5-naphthyridin-3-yl)methyl]piperazin-1-yl]-N-methyl-pyridine-2-carboxamide (Example 4 – pg. 15, line 36 through pg. 16, line 5),
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Example 4 is a compound of instant claims 1 and 2. For example, with respect to claim 2, M5 is -CR6R7-CR8R9- with R6 being ethyl and R7-R9 being H; M6 is N and Rb is hydrogen; L1 is -(CH2)1-; M1 and M2 are N, Rc is hydrogen, n5 and n6 are each one, and the variable bond is single; L2 is -(CH2)1-; ring D is aryl (phenyl) and Rd is hydrogen; and L3 is a bond and R1 is hydrogen.
Claim 3, depending from claim 1, recites compounds of the narrower formula (II)
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where the variable groups are as defined. Packer Example 4 is a species of formula (II) where Ra is ethyl; Rb is hydrogen; L1 is CH2; ring C is piperazyl and Rc is hydrogen; Rd is hydrogen; L3 is -(CH2)nC(O)NRaa(CH2)n1- where n is zero, Raa is hydrogen, and n1 is one; and R1 is hydrogen (other of the assorted definitions could be used to arrive at the same result).
Claim 4, depending from claim 1, recites compounds of the narrower (relative to the formula of claim 1) formula (IV)
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Packer Example 4 is a species of formula (IV) where Ra is ethyl; Rb, Rc, and Rd are hydrogen; M1 is N; ring D is pyridyl; L3 is -(CH2)nC(O)NRaa(CH2)n1- where n is zero, Raa is hydrogen, and n1 is one; and R1 is hydrogen.
With respect to claim 5, depending from claim 1, ring C of Packer Example 4 is piperazinyl, the first listed option in claim 5. With respect to claim 6, ring D of Packer Example 4 is pyridyl, a C5-10 heteroaryl. With respect to claim 7, R1 of Packer Example 4 is hydrogen. While this claim specifies alternatives for different variable groups when present (e.g. R11, R22, R33, R44, R55, and R66, the claim does not require them to be present. With respect to claim 8, instant Ra of Packer Example 4 of Brown is ethyl (alkyl). With respect to claim 9, instant Rb of Packer Example 4 is hydrogen. With respect to claim 10, instant Rc of Packer Example 4 is hydrogen. With respect to claim 11, instant Rd of Packer Example 4 is hydrogen.
Claim 18 recites a method for preparing a compound of formula (III) – i.e. claim 2. The method comprises reacting compounds of formulae (III-1) and (III-2) to produce a compound of formula (III):
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where X is a halogen.
As discussed above, Example 4 of Packer is a compound of formula (III). Packer further teaches reacting 7-(chloromethyl)-3-ethyl-1H-1,5-naphthyridin-2-one (Intermediate 17) with N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (Intermediate 13) to produce Example 4 (pg. 15, line 36 through pg. 16, line 20).
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This is an instance of the method of claim 18.
With respect to claim 19, Packer teaches various intermediates, such as intermediate 13 (reaction scheme at top of pg. 14), which is a compound of claim 19. With respect to claim 20, Packer teaches a pharmaceutical composition comprising a therapeutically effective amount of a disclosed PARP inhibitor and at least one pharmaceutically acceptable diluent, excipient, or inert carrier. (pg. 2, lines 26-28). With respect to claims 22-23, Packer teaches a method of treating diseases or conditions in which inhibition PARP1 is beneficial, comprising administering to a patient in need thereof an effective amount of a disclosed compound and further teaches that the disease state can be cancer, such as breast cancer (pg. 3, lines 7-121).
Allowable Subject Matter
Claims 13-17 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached on (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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629