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 .
Claims 1-12 are currently pending.
Priority
The instant application claims priority as follows:
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Claims 1-5, 7-9 and 11-12 do not find support in the foreign priority applications CN 202111375066.5 (filed 11/19/2021), CN 2021/11522026.9 (filed 12/14/2021) or CN 202210026917.3 (filed on 01/14/2022). This is apparent after comparing compound structures. No English language translation of the certified copies of the foreign priority have been submitted
It is not clear if claims 1-5, 7-9 and 11-12 find support in the foreign priority application CN 202211196794.4 (filed 09/30/2022) because no English language translation of the certified copy of the foreign priority has been submitted.
The effective filing date of claims 1-5, 7-9 and 11-12 is considered to be the filing date of the international application, which is 11/18/2022.
Claim 6 effective filing date appears to be 11/19/2021.
Response to Election/Restriction
Applicant’s election with traverse, of Group I, claims 1-9, 11 and 12, drawn to a compound of Formula (I-A), (I), or (II), and species compound #14
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(of claim 8), in the reply filed on August 21, 2026 is acknowledged. Claims 1-9, 11 and 12 read on the elected species.
The traversal is on the grounds that Group II contains all the structural limitations of Group I.
This is not found persuasive because that is not the standard for a lack of unity of invention under 37 CFR 1.475. Unity of invention exists when there is a technical relationship among the claimed inventions involving a special technical feature. The expression “special technical feature” means those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art. In the lack of unity requirement of July 9, 2026, it was stated that the compounds lack a significant structural element qualifying as the special technical feature. Additionally, the compounds were considered as the technical feature, however, it was stated that such technical feature was known in view of the references cited in the International Search Report. See the prior art rejections below. Since the compounds are not novel or inventive over the prior art, no “special technical feature” exists for subject matter that is common to all the claims. See PCT International Search and Preliminary Examination Guidelines, as in force from March 25, 2004, chapter 10, page 80 section 10.21, Example 1 which deals exactly with this situation, stating “However, if substance X is known in the art, unity would be lacking because there would not be a special technical feature common to all the claims.” Whether a particular technical feature makes a “contribution” over the prior art, and therefore, constitutes a “special technical feature”, is considered with respect to novelty and inventive step (see MPEP 1850).
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claim 10 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 07/09/2026.
Examination
Examination will begin with the elected species. In accordance with MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and applicable art was identified. Therefore, examination was stopped and art has been applied against the claims. The entire scope of claims 1-9, 11 and 12 has not yet been examined in accordance with Markush search practice. Pursuant to M.P.E.P. §803.02, the claims were examined with respect to the elected species and further with respect to the compounds in the rejections below. The prior art search will not be extended unnecessarily to cover all non-elected species.
Subject matter outside of the searched/examined scope and claim 10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions there being no allowable generic or linking claim.
Claims 1-9, 11 and 12 are the subject of this Office Action.
Specification Objections
The disclosure is objected to because of the following informalities:
The amendment filed on May 15, 2024 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: “the disclosure of which are hereby incorporated by reference in its entirety”. See page 1.
MPEP 211.02(a) states that “When a benefit claim is submitted after the filing of an application, the reference to the prior application cannot include an incorporation by reference statement specifying of the prior application unless an incorporation by reference statement specifying of the prior application was presented upon filing of the application. See Dart Indus. v. Banner, 636 F.2d 684, 207 USPQ 273 (C.A.D.C. 1980). An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a) ).”
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The instant application is a 371 application which has an International filing date of November 18, 2022. The incorporation by reference statement is being added by way of a Preliminary Amendment filed on May 15, 2024, which is after the instant application’s International filing date. Therefore, the “incorporation by reference” statement being added is deemed new matter.
Applicant is required to cancel the new matter in the reply to this Office Action.
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 1-7 and 9 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.
In claim 1, Z1-Z3 are each selected from N or C. A bare “C” leaves the valence and substitution of that ring atom undefined. The boundaries of ring B containing Z1-Z3 cannot be determined.
Claims 1, 6 and 7 recite A is “a 4- to 12-membered fused ring” or “a 4- to 12-membered bridged ring.” A fused or bridged bicyclic ring system cannot have only 4 members, so the claimed lower limit is inconsistent, and the scope of A is unclear.
Dependent claims are rejected for containing the same issues.
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.
Claims 11 and 12 are 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 11 depends of claim 6, however, claim 11 recites species in which ring B is a five-membered ring, R2 is a heteroaryl ring and species in which the quinoxaline ring is substituted at 5-position with fluoro. Claim 12 depends of claim 7, claim 7 fixes a ring nitrogen next to the fused carbon, requires ring B to be a six-membered aryl or heteroaryl, and limits R2 as in claim 6. However, claim 12 recites species in which ring B is a five-membered ring, species in which R2 is a heteroaryl ring, and species that lack the ring nitrogen next to the fused carbon. 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 § 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 6 is rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Angibaud et al. (US 8,404,713).
The prior art teaches compounds and compositions comprising a pharmaceutically acceptable carrier, and their use for the treatment of PARP-mediated disorders. The compound of formula
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was taught as PARP1 inhibitor at column 70 as Example B15, Preparation of Compound 17.
Claim 6 is rejected under 35 U.S.C. 102(a)(2) and claim 7 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being clearly anticipated by Trzoss et al. (WO 2022/225934-filed on April 19, 2022, claiming priority of
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).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
The prior art teaches compounds and compositions comprising a pharmaceutically acceptable carrier, and their use for the treatment of PARP-mediated disorders. Some compounds supported by priority doc of 05-03-2021 are exemplified below:
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(R2 is C2 substituted alkyl)
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(R2 is C3 substituted alkyl).
Some compounds supported by priority doc of 10-12-2021 are exemplified below:
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.
Claims 1-5, 7-9 and 11-12 are rejected under 35 U.S.C. 102(a)(2) as being clearly anticipated by Hoffman et al. (WO 2023/141290, claiming priority of
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).
The effective filing date of claims 1-5, 7-9 and 11-12 is considered to be the filing date of the international application, which is 11/18/2022.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
The prior art teaches Applicant’s elected species compound #14 at Table 1, as compound
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, and compositions comprising a pharmaceutically acceptable carrier, and their use for the treatment of PARP-mediated disorders. Other compounds that read on the instant claims are also taught in Table 1, for example
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. The compound species is supported by priority doc of 63/301,907, of effective filing date 21 January 2022.
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.
Claim(s) 1-9, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Angibaud et al. (US 8,404,713), in view of Johannes et al.(US 2021/0040084) and Johannes et al. (J. Med. Chem. 2021, 64(19), 14498-14512), and further in view of Trzoss et al. (WO 2022/225934, equivalent to US 2022/0348574-filed on April 19, 2022, claimed priority of
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).
Applicant elected compound #14
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. The structure of compound #14 is drawn in instant claims 8, 11 and 12.
Determination of the scope and content of the prior art (MPEP §2141.01)
Angibaud et al. teach 3-ethylquinolinones linked through -CH2- to a 4-aryl or 4-heteroaryl piperazine as PARP1 inhibitors and compositions comprising a pharmaceutically acceptable carrier. Compound 17 (column 70 as Example B15) carries a 5-cyanopyridin-2-yl group
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and inhibits PARP1 with a pIC50 of 9.063 (Table 3). Compound 17 is claimed specifically in patented claim 6.
Johannes et al. teaches azaquinolone PARP inhibitors linked through -CH2- to a 4-(pyridin-3-yl)piperazine
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(including the compound at [0021-0022]). It teaches that these azaquinolones have surprisingly high selectivity for PARP1 over PARP2, PARP3, PARP5a and PARP6, with low hERG activity (para [0010]). It also teaches pharmaceutical compositions with acceptable carriers and the treatment of cancer ([0012], [0027]).
Johannes (J. Med. Chem.) reports the discovery of the selective PARP1 inhibitor compound AZD5305.
The teachings of Trzoss et al. discussed above are incorporated herein. Compounds of formula
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were taught for the same use. Some compounds of claims 6 and 7 were anticipated by Trzoss. Trzoss teaches the same compound of Angibaud (#17):
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, in addition to many compounds containing the 1,5-naphthyridin-2-one-CH2-piperazine core:
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. See examples in Table 1, particularly examples 19, 82 and 128.
Ascertainment of the difference between the prior art and the claims (MPEP §2141.02)
The elected species compound #14 differs from compound 17 of the primary reference only in that the C-5 carbon of the quinolin-2-one is replaced by nitrogen, giving the 1,5-naphthyridin-2-one- scaffold.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
Before the effective filing date of this application, a person of ordinary skill in the art would have been motivated to select compound 17 as lead compound from the Angibaud patent, since it has a sub-nanomolar PARP1 inhibitory activity and it was specifically claimed in claim 6 of the patent. The artisan would have been motivated to replace its quinolin-2-one with the 1,5 naphthyridin-2-one of the secondary references because the secondary references teach that this aza replacement in the same type of core containing the -CH2-piperazine scaffold gives surprisingly high PARP1 selectivity and low hERG activity (see secondary references). The elected species was prima facie obvious.
Replacing a CH with N in a heteroaryl ring is a well known isosteric change, and Johannes and Trzoss show it was made successfully on this scaffold. There would have been a reasonable expectation of success in view of the secondary references, since the 7-ethyl-1,5-naphthyridin-2-one-CH2-piperazine-pyridin core core was previously made by the references.
Claim(s) 1-9, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Trzoss et al. (WO 2022/225934-filed on April 19, 2022, claimed priority of
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).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Determination of the scope and content of the prior art (MPEP §2141.01)
Some compounds of claims 6 and 7 were anticipated by Trzoss. The teachings of Trzoss et al. discussed above are incorporated herein.
Trzoss disclosed quinoline and 1,5-naphthyridine compounds of formula
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, such as compounds of formula
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, compositions with carriers, and their use as PARP1 inhibitors for the treatment of certain cancers.
Ascertainment of the difference between the prior art and the claims (MPEP §2141.02)
Applicant claims position isomers of compounds 128, 129, 131, 120 and 118 of Trzoss above, where a nitrogen on the pyridyl or pyrazine ring is at position 2 instead of at position 3. Applicant also claims position isomers of compounds of Trzoss above where the cyano group is at position 3, 4, 5 or 6 instead of at position 2 of the phenyl or pyridyl ring. The compounds have the same use as PARP1 inhibitors for the treatment of certain cancers.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
It has been held that compounds that differ only in the placement of substituents in a ring system are not patentable absent a showing of unexpected properties. See In re Jones, 74 USPQ 152 (CCPA 1947). Such structurally related compounds suggest one another and would be expected to share common properties absent a showing of unexpected results. In re Norris, 84 USPQ 458 (1950).
One of ordinary skill in the art would have been motivated to make the claimed position isomers of the prior art compounds of Trzoss above with the expectation that additional compounds useful as PARP1 inhibitors would be obtained. There could be nothing unexpected found in the compound defined by Applicant.
For example, the compound of Trzoss of formula
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rendered obvious the claimed compound of formula
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.
It is well established that position isomers are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the position isomers. This circumstance has arisen many times. See: Ex parte Englehardt, 208 USPQ 343, 349; In re Mehta, 146 USPQ 284, 287; In re Surrey, 138 USPQ 67; Ex Parte Ullyot, 103 USPQ 185; In re Norris, 84 USPQ 459; Ex Parte Naito, 168 USPQ 437, 439; Ex parte Allais, 152 USPQ 66; In re Wilder, 166 USPQ 545, 548; Ex parte Henkel, 130 USPQ 474; Ex parte Biel, 124 USPQ 109; In re Petrzilka, 165 USPQ 327; In re Crownse, 150 USPQ 554; In re Fouche, 169 USPQ 431; Ex parte Ruddy, 121 USPQ 427; In re Wiechert, 152 USPQ 247, In re Shetty, 195 USPQ 753; In re Jones, 74 USPQ 152, 154; and In re Mayne, 41 USPQ2d 1451 (in which the Court took notice of the extreme similarity between the amino acids Leucine and isoleucine: “In fact, Leu is an isomer of Ile -- an identical chemical formula with differences only in the chemical bonding of the atoms. The side chains…of Leu and Ile have the same number of hydrogen and carbon atoms…The structure of Leu and Ile alone suggest their functional equivalency” (at 1454-1455)). See In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).” See also MPEP 2144.09, second paragraph.
Trzoss et al. teach that the compounds are useful as PARP1 inhibitors for the treatment of cancer; artisan interested in such inhibitors would have found the compounds of the reference described above to be appropriate leads on the basis of their known biological activity. Once the artisan identified them as suitable lead compounds, their position isomers and homologs would have been obvious variants under MPEP 2144.09, second paragraph.
Moreover, Trzoss teaches formula (I) to include position isomers. The substituents on ring A may be at any position, and ring A may be connected at any position, while achieving retention of the compound’s activity as a PARP1 inhibitor:
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(p.15). Further, Trzoss teaches examples of position isomers:
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vs.
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. Thus, Trzoss suggested making the position change in the compounds with the expectation of obtaining compounds for the same use.
Conclusion
Not every piece of prior art found in the search has been applied against the instant claims. See MPEP 904.03.
Provisional applications for WO 2022/225934 A1 to Trzoss and WO 2023/141290 to Hoffman are available in Patentscope of WIPO.
Claims 1-9 and 11-12 are rejected. No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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