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 is a continuation of 17/363,099 06/30/2021 abandoned which is a continuation of 16/734,566 01/06/2020 U.S. patent 11,084,812 which is a divisional of 16/127,229 09/11/2018 U.S. patent 10,590,122 which claims benefit of 62/711,959 07/30/2018 and claims benefit of 62/556,763 09/11/2017.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/556,763, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The prior filed application as discussed above fails to provide adequate support for the structural formula recited in claim 1 when:
Cy is -(C3-C5 or C7)cycloalkyl, bridged (C6-C12) cycloalkyl; or a 4-10 membered heterocyclic ring in addition to the optionally recited substituents, see instant claim 1, line 5-7;
where the (C1-C5)alkyl of R1 is optionally substituted with -OH, see instant claim 1, line 11;
where R3 is -CH2-phenyl; -(C3-C7)cycloalkyl; -CH2-(C3-C7)cycloalkyl, -CH2-monocyclic 3-7 membered heterocyclic ring or the optional substituents recited, see instant claim 1, lines 12-17;
where R2 is -NRaC(O)NRa-(C7)cycloalkyl, see instant claim 1, line 20;
wherein the -(C3-C7)cycloalkyl in the group represented by R2 is optionally =O, see instant claim 1, pg. 3, line 5;
wherein the phenyl in the group represented by R2 is optionally -CN, see instant claim 1, pg. 3, line 8;
wherein the heterocyclic ring in the group represented by R2 is optionally -ORa, see instant claim 1, pg. 3, line 10; and
wherein the heteroaromatic ring in the group represented by R2 is optionally -CN, see instant claim 1, pg. 3, line 14.
Therefore, the Examiner interprets claims 1, 35-36 and 48 have a priority date of 07/30/2018.
The Examiner also interprets claim 2 has a priority date of 09/11/2017.
Claim Status
The preliminary amendment to the claims filed 01/13/2025 has been entered.
Claims 3-34, 37-47 and 49-55 are canceled.
Thus, claims 1-2, 35-36 and 48 as amended are examined on the merits herein.
Claim Objections
Claims 1, 2 and 48 are objected to because of the following informalities:
(A) Claim 1, line 22, and Claim 2, pg. 4, line 1, are both clearly missing an “or” before the last recited species within the Markush group, specifically before “-NRaC(O)NRa-monocyclic 5-6 membered heteroaromatic ring”.
To resolve these objections Applicant can insert an “or” as recited above.
(B) Claim 48 recites “a DNA repair inhibitor, a DNA damage response (DDR) inhibitor”, however, the Examiner respectfully notes the compound of claim 1 is a DNA repair or damage response inhibitor, see specification, pg. 2, summary of the invention, paragraph 1.
To resolve this objection Applicant can insert the phrase “an additional agent comprising” immediately before the recitation “a DNA repair” as recited above.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 36 and 48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating lymphoma;
select compounds Ex. 29 (see pg. 160), Ex. 31 (see pg. 160), Ex. 66A (see pg. 165), and Ex. 67A (see pg. 165) in treating leukemia and head and neck cancer;
select compounds Ex. 66A and Ex. 67A in treating gastric cancer;
select compounds Ex. 29, Ex. 66A and Ex. 67A in treating ovarian cancer; and
selected compound Ex. 67A in treating pancreatic cancer, does not reasonably provide enablement for treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a result, substantiation of utility and its scope is required when utility is speculative, sufficiently unusual or not provided, and enablement must be commensurate with the scope of the claim language. As MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”.
As stated in MPEP § 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”.
The applicant’s attention is drawn to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), where the court set forth eight factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. They are: (1) The nature of the invention; (2) The state of the prior art; (3) The level of skill in the art; (4) The
predictability or lack thereof in the art; (5) The breadth of the claims; (6) The amount of direction or guidance present; (7) The presence or absence of working examples; and (8) The quantity of experimentation needed.
It is noted that all of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
The nature of the invention: The invention is directed at a method for treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se as recited in claim 36 by administering the compounds recited in claim 1.
Moreover, the Examiner notes claim 48 is drawn to co-administering an effective amount of a DNA repair inhibitor, a DNA damage response (DDR) inhibitor, a DNA damaging agent or an immunomodulatory agent.
Accordingly, to be enabled for the full scope of treatment, one skilled in the art must reasonably be able to ascertain which agents are effective, obtain said agents, and successfully use said agents for treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se.
The Examiner notes the compounds recited in claim 1 are disclosed as inhibitors of the enzyme RAD51, see specification, pg. 1, background of the invention, paragraph 1.
Additionally, Applicant provides EC50 data of these compounds in a cell killing assay against the Daudi cell line (AID positive) which is discussed in greater detail below, see specification, pg. 155, 3. Procedure, paragraph 1.
The state of the prior art: The state of the art does not recognize RAD51 inhibitors, e.g. the compounds recited in claim 1, as useful in treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se.
Attention is drawn to Castro et al. (Published 20 August 2024, US-12064419-B2, PTO-892), Castro discloses methods of using RAD51 inhibitors, see title. Castro exemplifies said RAD51 inhibitor within the generic structural formula (I), see Col. 40, line 30 – Col. 41, line 40. The Examiner respectfully notes the compounds of generic structural formula (I) of Castro encompass the compounds of the structural formula recited in instant claim 1.
Castro discloses the RAD51 inhibitors of the disclosure reduces the repair of activation-induced cytidine deaminase (AID or AICDA) induced DNA double strand breaks, leading to AID-dependent cytotoxicity in malignant cells, see Col. 3, lines 55-65.
Castro discloses RAD51 inhibitors of the disclosure inhibit homologous recombination by altering the nucleocytoplasmic distribution of RAD51 following DNA damage induction, see Col. 3, lines 55-65.
Castro alleges diseases which can be ameliorated by inhibition of RAD51 include treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease, see Col. 4, lines 5-10.
However, the Examiner notes Castro provides EC50 data of these compounds in a cell killing assay against the Daudi cell line (AID positive) in Table 1, see Col. 268-294; the Examiner notes Daudi cells are a lymphoma cell line, see Castro, Col. 294, Table 1, cell line, Daudi.
Additionally, Castro provides support for the activity of exemplified compounds in Example 74 within Table 4, where Table 4 discloses EC50 data associated to four exemplified RAD51 inhibitors, Ex. 29, Ex. 31, Ex. 66A, and Ex. 67A against different expression levels of activation-induced cytidine deaminase (AID or AICDA) within various cancer cell types which consist of Daudi, WSU-FSCCL, and U-698-M (lymphoma); CCRF-SB and KG-1 (leukemia); KYSE-70 and KYSE-510 (head and neck); SNU-1 and SNU-5 (gastric); and TOV-1120D and OV-56 (ovarian), see Col. 2945-295, Table 4.
Castro provides Example 80 which describes the IC50 activity data of Ex. 67A, as discussed above, screened against various pancreatic cancer cell lines, the data is provided in Table 6, see Col. 295-296 and Table 6.
Castro further provides in vivo data of anti-tumor activity of Ex. 67A in three different pancreatic PDX models, see Example 81, Col. 296-298 and Example 82, Col. 298-299.
Although Castro discloses the compounds of the generic structure of formula (I) as inhibitors of RAD51, no compounds are screened in a RAD51-based assay. The Examiner also notes, in view of Castro’s disclosure, the use of Castro’s compounds as RAD51 inhibitors seem to be dependent on their activity to reduce the repair mechanism of activation-induced cytidine deaminase (AID or AICDA) induced by Castro’s disclosed compounds as discussed above, the Examiner further notes said interactions with AID may provide the environment to alter RAD51’s nucleocytoplasmic distribution following DNA damage induction as disclosed by Castro above.
Moreover, the Examiner particularly notes Castro does not screen any disclosed compounds in any model that would provide support for treating any autoimmune disease, any immune deficiency, or any neurodegenerative disease as discussed above.
Furthermore, with particular attention to treating cancer per se, although the state of the art provides support for treating selected types of cancers with selected compounds as discussed above, as disclosed and demonstrated by Castro above, in view of Qin et al. (Published 24 September 2025, Med Research, Vol. 1, Issue 3, pp. 359-377, PTO-892) Qin discloses a review of the state of the art of Rad51 and its role in DNA repair, tumorigenesis, and immune regulation, see pg. 359, title. Qin discloses accumulating evidence reveals a paradoxical association between Rad51 dysregulation and tumor progression – although its deficiency predisposes cells to genomic instability and tumor initiation, its overexpression frequently correlates with advanced malignancies, therapy resistance, and poor clinical outcomes. This dual nature of Rad51 in oncogenesis, functioning as both tumor suppressor and tumor promoter depending on the cellular context, underscoring the complexity of DNA repair machinery in cancer biology. See pg. 363, right column, 3. Rad51 and Tumors, paragraph 1.
Qin discloses accumulating evidence demonstrates that Rad51 is frequently overexpressed in multiple human malignancies, including breast, lung, ovarian, and prostate cancers, see pg. 364, left column, 3.1 Rad51 Expression in Tumors.
However, Qin discloses the survival and metastatic functions of Rad51 in cancer cells are modulated by multiple regulatory factors, see pg. 364, right column, paragraph 1.
Additionally, Qin discloses studies have shown that inhibition of Rad51 expression or function can enhance the sensitivity of tumor cells to immune checkpoint inhibitors, thereby improving the efficacy of immunotherapy, see pg. 368, right column, 4.3 Antitumor Immunotherapy Strategies Targeting Rad51, paragraph 1.
Therefore, as whole Qin discloses the potential use of Rad51 inhibitors in cancers where Rad51 is overexpressed. Accordingly, in view of the disclosure of Qin, the Examiner reasonably interprets the inhibition of Rad51 in cancer per se is not enabled as administering said Rad51 inhibitor, for example the compounds of claim 1 as recited in claim 36, would not reasonably provide a therapeutic effect if Rad51 is not overexpressed and thus involved in the cancer as a tumor promoter as disclosed by Qin as a whole above.
Moreover, in the context of Rad51’s relationship with immune response, Qin discloses homologous recombination repair (HRR) defects caused by Rad51 may be an activating endogenous factor that upregulates the STING pathway as studies have shown that the innate immune signaling pathway is mediated by cGAS‐STING, see pg. 366, right column, 4.1 Relationship Between Rad51 and Immune Response.
However, Qin discloses it is not clear how Rad51 precisely regulates immune‐related signaling pathways (such as interferon responses); and there is a lack of systematic research on the specific interactions between Rad51 and different immune cell subsets, such as Treg and NK cells, etc, see pg. 367, left column, paragraph 1.
Thus, in viewing the state of the art as discussed above in its totality, the actual use of the compounds recited in claim 1 for treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se in a subject in need thereof is currently unclear.
The relative skill in the art: The relative skill of those in the art is high.
The predictability or lack thereof in the art: As discussed above, the use of the compounds recited in claim 1 in treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se is unknown. As a result, at the time of the invention the field of therapy to treat cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se by administering said compounds recited in claim 1 were limited. Therefore, at the time of the invention the field of therapeutic use to treat cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se by administering said compounds recited in claim 1 were relatively underdeveloped and unpredictable.
Furthermore, although claim 48 is drawn to co-administering an effective amount of an additional agent comprising a DNA repair inhibitor, a DNA damage response (DDR) inhibitor, a DNA damaging agent or an immunomodulatory agent; in view of this high level of generality, this limitation does not provided further predictability in treating any cancer, any autoimmune disease, any immune deficiency, or any neurodegenerative disease claimed by Applicant above.
The breadth of the claims: The breadth of treatment claimed is extremely broad as it is reasonably interpreted by the Examiner to encompass a method for treating any cancer, any autoimmune disease, any immune deficiency, or any neurodegenerative disease by administering a compound of claim 1, or a pharmaceutically acceptable salt thereof.
The amount of direction or guidance present: The specification suggests a method for treating a cancer, an autoimmune disease, an immune deficiency, or a neurodegenerative disease, see specification, pg. 3, second full paragraph, by inhibiting RAD51 by binding to MDC1 and causing reduced ability to form active complexes of RAD51, see pg. 3, fifth full paragraph.
However, Applicant’s suggestion of using said compounds recited in claim 1 for treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se via inhibition of RAD51 as the mechanism of action is based on Applicant’s speculation and is not supported by any existing experimental results in the art regarding the administration of the compounds recited in claim 1 to treat any cancer, any autoimmune disease, any immune deficiency, or any neurodegenerative disease in view of the state of the art above.
The presence or absence of working examples: Applicants’ specification discusses Example 75, a screening technique using AID positive cells and AID negative cells to determine potency of Applicant’s disclosed compounds, see pg. 155, Example 75, 1. Background.
The procedure screened exemplified compounds of Applicant in a cell killing assay in the Daudi cell line (AID positive), see pg. 155, Example 75, 3. Procedure; and the results of said assay are provided in Table 1, see pg. 157-166. The Examiner notes the cell killing assay described above corresponds to the cell killing assay disclosed by Castro in the state of the art above.
Applicant provides the activity of exemplified compounds in Example 78 in Table 4, where Table 4 discloses EC50 data associated to four exemplified RAD51 inhibitors, Ex. 29, Ex. 31, Ex. 66A, and Ex. 67A against different expression levels of activation-induced cytidine deaminase (AID or AICDA) within various cancer cell types which consist of Daudi, WSU-FSCCL, and U-698-M (lymphoma); CCRF-SB and KG-1 (leukemia); KYSE-70 and KYSE-510 (head and neck); SNU-1 and SNU-5 (gastric); and TOV-1120D and OV-56 (ovarian), see pp. 168-169, Table 4. The Examiner notes the EC50 data discussed above corresponds to the EC50 data disclosed in Table 4 of Castro in the state of the art above.
Moreover, Applicant alleges AID expressing cells are dependent upon RAD51 for survival and by inhibiting RAD51 in AID positive cells results in cytotoxic effects. See specification, pg. 155, Example 75, 1. Background. Accordingly, the Examiner notes the compounds screened within Example 75 exemplified in Table 1 above provides support the compounds recited in claim 1 are RAD51 inhibitors.
However, the Examiner notes Applicant does not provide a scientific rationale based on evidence for why such a distinction is substantive in view of the state of the art as discussed above, as the Examiner reiterates based on the state of the art it appears enablement for treating cancer is dependent on said cancer overexpressing RAD51, additionally RAD51’s role in immune response is currently unclear and lacks systematic research, and thus these are critically important considerations in view of the broad scope of diseases Applicant is claiming to treat by administering the compounds recited in claim 1 as discussed above.
Furthermore, the Examiner notes Applicant does not screen any disclosed compounds in any model that would provide support for treating any autoimmune disease, any immune deficiency, or any neurodegenerative disease as discussed above.
Finally, the Examiner notes the experimental examples provided by Applicant above are not an actual example of treating any cancer in a subject. Rather, it’s based on the extrapolation of the role RAD51 may have on AID, particularly AID positive cells in view of Applicant’s disclosure above, and the role RAD51 may have as a tumor promoter on cancer as a genus in view of the state of the art, as Applicants hypothesizes the AID activity level in cancer cells, its potential interface with RAD51 in cancer cells, and the result of said interface in producing a potential therapeutic effect in any cancer.
Note the lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the use of the compounds recited in claim 1 in treating cancer, autoimmune disease, immune deficiency, or neurodegenerative disease per se in a subject.
The quantity of experimentation needed: In order to translate the suggestions in Applicants’ disclosure into an actual therapeutic model with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would have to undertake a novel and extensive research program to show that any compound according to instant claim 1 could successfully treat any cancer, any autoimmune disease, any immune deficiency, or any neurodegenerative disease in a subject. Therefore, because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of disease, for which there is no single cause or mechanism of disease, it would constitute an undue and unpredictable search and experimental burden.
Genentech, 108 F.3d at 1366, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art, the breadth of the claims, and the lack of guidance or working examples, Applicants fail to provide sufficient information to practice the claimed invention.
Henceforth, the 102 rejection as written below captures what Applicant has enablement for as discussed above.
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)(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.
Claims 1, 35-36 and 48 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Cyteir Therapeutics, Inc. (US 10336746, US 10590122, or US 11084812 benefitted from provisional application 62/556,763 filed on 09/11/2017, PTO-892).
The applied references have a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claims 1, 35-36 and 48:
(I) US 10336746 teaches RAD51 inhibitors, see title.
‘746 exemplifies said inhibitor as Example 67A depicted as,
PNG
media_image1.png
196
694
media_image1.png
Greyscale
, see Col. 223, Table 1, Ex. 67A.
The Examiner notes Ex. 67A, reads on the compounds of claim 1 when Cy is C6-cycloalkyl; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
‘746 teaches a pharmaceutical composition comprising a compound described herein and a pharmaceutically acceptable carrier or diluent (e.g. the composition, required in claim 35), see Col. 2, lines 40-45.
‘746 teaches treating lymphoma by administering to the subject an effective amount of one or more disclosed compounds or the corresponding pharmaceutical composition (e.g. the method, required in claim 36), see Col. 30, lines 29-35.
‘746 teaches co-administering an effective amount of a DNA damaging agent to the subject being treated for cancer, in addition to an effective amount of a disclosed RAD51 inhibitor (e.g. the DNA damaging agent, required in claim 48), see Col. 41, lines 31-36.
Thus, in view of the teachings of the ‘746 patent, the ‘746 patent anticipates claims 1, 35-36 and 48.
(II) US 10590122 teaches RAD51 inhibitors, see title.
‘122 exemplifies said inhibitor as Example 67B depicted as,
PNG
media_image2.png
198
638
media_image2.png
Greyscale
, see Col. 249, Table 1, Ex. 67B.
The Examiner notes Ex. 67B, reads on the compounds of claim 1 when Cy is C6-cycloalkyl; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
‘122 teaches a pharmaceutical composition comprising a compound described herein and a pharmaceutically acceptable carrier or diluent (e.g. the composition, required in claim 35), see Col. 2, lines 37-40.
‘122 teaches treating lymphoma by administering to the subject an effective amount of one or more disclosed compounds or the corresponding pharmaceutical composition (e.g. the method, required in claim 36), see Col. 31, lines 8-13.
‘122 teaches co-administering an effective amount of a DNA damaging agent to the subject being treated for cancer, in addition to an effective amount of a disclosed RAD51 inhibitor (e.g. the DNA damaging agent, required in claim 48), see Col. 42, lines 50-55.
Thus, in view of the teachings of the ‘122 patent, the ‘122 patent anticipates claims 1, 35-36 and 48.
(III) US 11084812 teaches RAD51 inhibitors, see title.
‘812 exemplifies said inhibitor as either Example 67A or 67B depicted as,
PNG
media_image3.png
354
574
media_image3.png
Greyscale
, see Col. 251, Table 1, Ex. 67A and Ex. 67B.
The Examiner notes Ex. 67A and Example 67B read on the compounds of claim 1 when Cy is C6-cycloalkyl; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
‘812 teaches a pharmaceutical composition comprising a compound described herein and a pharmaceutically acceptable carrier or diluent (e.g. the composition, required in claim 35), see Col. 2, lines 42-45.
‘812 teaches treating lymphoma by administering to the subject an effective amount of one or more disclosed compounds or the corresponding pharmaceutical composition (e.g. the method, required in claim 36), see Col. 30, lines 47-52.
‘812 teaches co-administering an effective amount of a DNA damaging agent to the subject being treated for cancer, in addition to an effective amount of a disclosed RAD51 inhibitor (e.g. the DNA damaging agent, required in claim 48), see Col. 42, lines 17-22.
Thus, in view of the teachings of the ‘812 patent, the ‘812 patent anticipates claims 1, 35-36 and 48.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
(I) Claims 1-2 and 35 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-2 and 19 of prior U.S. Patent No. 10,590,122 B2 (Applicant: Cyteir Therapeutics, Inc., PTO-892). This is a statutory double patenting rejection.
Reference claims 1 and 2 recite an identical scope of compounds representing the structural formula as recited in Cy, X5, X6, R1, R3, and R2 as instantly claimed within the structural formula of instant claim 1 and instant claim 2 respectively.
Additionally, reference claim 19 recites an identical pharmaceutical composition as recited within instant claim 35.
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.
(II) Claims 1-2 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 10,336,746 B1 (Applicant: Cyteir Therapeutics, Inc., PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to pharmaceutical compositions comprising the compounds recited in instant claims 1-2.
Reference claim 1 recites a compound of the following structure depicted as,
PNG
media_image4.png
198
386
media_image4.png
Greyscale
or a pharmaceutically acceptable salt thereof.
Reference claim 2 recites a pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
The Examiner notes the compound of reference claim 1 reads on the generic structure recited in either instant claim 1 or instant claim 2 when Cy is -C6-cycloalkyl or cyclohexyl, respectively; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
Thus, reference claims 1-2 anticipate instant claims 1-2 and 35.
(III) Claims 1-2 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,084,812 B2 (Applicant: Cyteir Therapeutics, Inc., PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to compounds recited in instant claims 1-2 and methods of use thereof.
Reference claim 1 recites treating lymphoma, comprising administering to a subject in need thereof an effective amount of a compound represented by the following structural formula depicted as,
PNG
media_image5.png
194
434
media_image5.png
Greyscale
or a pharmaceutically acceptable salt thereof, where:
Cy is (C3-C7)cycloalkyl, bridged (C6-12)cycloalkyl, or a 4-10 membered heterocyclic ring;
When X5 is connected with a nitrogen ring atom, X5 is absent or when X5 is connected with a carbon ring atom X5 is NRa or O;
X6 is NRa or O;
R1 is (C1-C5)alkyl;
R3 is (C1-C5)alkyl, -CH2-phenyl, -(C3-C7)cycloalkyl, -CH2-(C3-C7)cycloalkyl, -CH2-monocyclic 3-7 membered heterocyclic ring, or monocyclic 3-7 membered heterocyclic ring;
R2 is -NRaC(O)O(C1-C4)alkyl; -NRaC(O)NRa(C1-C4)alkyl; -NRaC(O)O(C2-C4)alkenyl; -NRaC(O)NRa (C2-C4)alkenyl; -NRaC(O)O-(C3-C6)cycloalkyl; -NRaC(O)NRa-(C3-C7)cycloalkyl; -NRaC(O)O-phenyl; -NRaC(O)NRa-phenyl; -NRaC(O)O-monocyclic 3-7 membered heterocyclic ring; -NRaC(O)NRa-monocyclic 3-7 membered heterocyclic ring; -NRaC(O)O-monocyclic 5-6 membered heteroaromatic ring; or -NRaC(O)NRa-monocyclic 5-6 membered heteroaromatic ring; and
Ra is H or CH3.
Reference claim 2 depends from reference claim 1 and further recites:
Cy is cyclohexyl or a 6-membered monocyclic heterocyclic ring;
X5 and X6 is NRa or O;
R1 is (C1-C5)alkyl;
R3 is (C1-C5)alkyl or monocyclic 3-7 membered heterocyclic ring; and
R2 and Ra is as recited above.
The Examiner notes the recitations of reference claims 1-2 imply possession of the compounds recited within reference claims 1-2 so administered and further notes the scope of Cy, X5, X6, R1, R3, and R2 as recited in reference claims 1-2 read on instant claims 1-2 respectively.
Accordingly, the Examiner notes the recitations of reference claims 1-2 anticipate instant claims 1-2 and 36, where applicable.
(IV) Claims 1-2 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,064,419 B2 (Applicant: Cyteir Therapeutics, Inc., PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to compounds recited in instant claims 1-2 and methods of use thereof.
Reference claim 1 recites treating pancreatic cancer comprising administering to a subject in need thereof an effective amount of compound 67A depicted as,
PNG
media_image6.png
162
402
media_image6.png
Greyscale
or a pharmaceutically acceptable salt thereof.
The Examiner notes the compound of reference claim 1 reads on the generic structure recited in either instant claim 1 or instant claim 2 when Cy is -C6-cycloalkyl or cyclohexyl, respectively; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
The Examiner notes the recitations of reference claim 1 imply possession of the compound recited within reference claim 1 so administered.
Accordingly, the Examiner notes the recitations of reference claim 1 anticipate instant claims 1-2 and 36.
(V) Claims 1-2, 36 and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,607,404 B2 (Applicant: Cyteir Therapeutics, Inc., PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to compounds recited in instant claims 1-2 and methods of use thereof.
Reference claim 1 recites treating a hematological cancer and a solid tumor comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the following structure depicted as,
PNG
media_image7.png
226
444
media_image7.png
Greyscale
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a PARP inhibitor selected from olaparib, veliparib, and niraparib or a pharmaceutically acceptable salt thereof (e.g. the DNA repair inhibitor, required in instant claim 48).
The Examiner notes the compound of reference claim 1 reads on the generic structure recited in either instant claim 1 or instant claim 2 when Cy is -C6-cycloalkyl or cyclohexyl, respectively; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
The Examiner notes the recitations of reference claim 1 imply possession of the compound recited within reference claim 1 so administered.
Accordingly, the Examiner notes the recitations of reference claim 1 anticipate instant claims 1-2, 36 and 48.
(VI) Claims 1-2 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/766,813 (Applicant: Cyteir Therapeutics, Inc., filed 07/09/2024, amended claim set filed 11/25/2024) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to compounds recited in instant claims 1-2 and methods of use thereof.
Reference claim 1 recites treating pancreatic cancer comprising administering to a subject in need thereof an effective amount of a compound represented by the following structural formula depicted as,
PNG
media_image8.png
104
248
media_image8.png
Greyscale
or a pharmaceutically acceptable salt thereof, where:
Cy is (C3-C7)cycloalkyl, bridged (C6-12)cycloalkyl, or a 4-10 membered heterocyclic ring;
When X5 is connected with a nitrogen ring atom, X5 is absent or when X5 is connected with a carbon ring atom X5 is NRa or O;
X6 is NRa or O;
R1 is (C1-C5)alkyl;
R3 is (C1-C5)alkyl, -CH2-phenyl, -(C3-C7)cycloalkyl, -CH2-(C3-C7)cycloalkyl, -CH2-monocyclic 3-7 membered heterocyclic ring, or monocyclic 3-7 membered heterocyclic ring;
R2 is -NRaC(O)O(C1-C4)alkyl; -NRaC(O)NRa(C1-C4)alkyl; -NRaC(O)O(C2-C4)alkenyl; -NRaC(O)NRa (C2-C4)alkenyl; -NRaC(O)O-(C3-C6)cycloalkyl; -NRaC(O)NRa-(C3-C7)cycloalkyl; -NRaC(O)O-phenyl; -NRaC(O)NRa-phenyl; -NRaC(O)O-monocyclic 3-7 membered heterocyclic ring; -NRaC(O)NRa-monocyclic 3-7 membered heterocyclic ring; -NRaC(O)O-monocyclic 5-6 membered heteroaromatic ring; or -NRaC(O)NRa-monocyclic 5-6 membered heteroaromatic ring; and
Ra is H or CH3.
The Examiner notes the recitations of reference claim 1 imply possession of the compound recited within reference claim 1 so administered; and accordingly, the recitations of reference claim 1 make obvious the compounds of instant claims 1-2.
Thus, the recitations of reference claim 1 make obvious instant claims 1-2 and 36.
Furthermore, although the ‘813 application recites treating pancreatic cancer using the compounds recited in reference claim 1 above, the Examiner respectfully and particularly notes the specification only provides evidence for treating pancreatic cancer with Ex. 67A, see specification pg. 218 for the recited structure; and Examples 80-82 on pp. 223-229 for the in vitro and in vivo experimental studies; and consequently the Examiner notes said evidence is commensurate with the 112(a)-scope of enablement rejection written above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(VII) Claims 1-2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/798,938 (Applicant: Cyteir Therapeutics, Inc., filed 08/09/2024, amended claim set filed 12/20/2024, Notice of Allowability mailed 06/11/2026) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to compounds recited in instant claims 1-2.
Reference claim 1 recites preparing compound A depicted as,
PNG
media_image9.png
136
258
media_image9.png
Greyscale
or a pharmaceutically acceptable salt thereof.
The Examiner notes the compound of reference claim 1 reads on the generic structure recited in either instant claim 1 or instant claim 2 when Cy is -C6-cycloalkyl or cyclohexyl, respectively; X5 is NRa, wherein Ra is H; X6 is O; R1 is C4-alkyl; R3 is C3-alkyl; and R2 is -NRaC(O)OC3-alkyl, wherein Ra is H.
The Examiner notes the recitations of reference claim 1 imply possession of the compound recited within reference claim 1 so prepared.
Accordingly, the Examiner notes the recitations of reference claim 1 anticipate instant claims 1-2.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARET J CREWS/Examiner, Art Unit 1691
/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
Prosecution Insights