DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending.
Status of Priority
This application claims the benefits of priority to U.S. Provisional Application No. 63/603,412, filed on November 28, 2023.
Information Disclosure Statement
The instant application is accompanied with no IDS. Examiner would like to remind Applicant that “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section. The duty to disclose information exists with respect to each pending claim until the claim is cancelled or withdrawn from consideration, or the application becomes abandoned. Information material to the patentability of a claim that is cancelled or withdrawn from consideration need not be submitted if the information is not material to the patentability of any claim remaining under consideration in the application. There is no duty to submit information which is not material to the patentability of any existing claim. The duty to disclose all information known to be material to patentability is deemed to be satisfied if all information known to be material to patentability of any claim issued in a patent was cited by the Office or submitted to the Office in the manner prescribed by §§ 1.97(b) -(d) and 1.98. However, no patent will be granted on an application in connection with which fraud on the Office was practiced or attempted or the duty of disclosure was violated through bad faith or intentional misconduct.” See 37 C.F.R. 1.56 for more details.
Specification - Abstract
The abstract is objected to because of the following informalities:
For consistency with the claims, the 1st sentence of the abstract should read:
“Disclosed herein are phenoxido copper compounds or complexes, hydrates, solvates, geometric isomers, or salts thereof…”
To be consistent with MPEP 2173.05(h) regarding alternative limitations, the 1st sentence of the abstract should further read:
“… where the compounds have a chemical structure selected from the group consisting of: [Cu2(L1)2](ClO4)2, [Cu2(L2)2](ClO4)2, [Cu2(L3)2], [Cu2(L4)2], [Cu2(L5)2(H2O)]·2H2O, [Cu2(L6)2(H2O)]·2H2O, and catena-[Cu(μ-L7)].”
Notes about the changes in the above bullet point:
[Cu2(L4)2] is removed because it appears to be the same as “[Cu2(L4)2]” which is printed right after.
The “2” between “(L5)” and “(H2O)” in “[Cu2(L5)2(H2O)]·2H2O” should be in subscript as shown above.
The “2” between “(L6)” and “(H2O)” in [Cu2(L6)2(H2O)]·2H2O should be in subscript as shown above.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1, 9, and 15 are objected to because of the following informalities:
To be consistent with MPEP 2173.05(h) regarding alternative limitations, claims 1 and 9 should read:
“… a chemical structure selected from the group consisting of: [Cu2(L1)2](ClO4)2, [Cu2(L2)2](ClO4)2, [Cu2(L3)2], [Cu2(L4)2], [Cu2(L5)2(H2O)]·2H2O, [Cu2(L6)2(H2O)]·2H2O, and catena-[Cu(μ-L7)]…”
Notes about the changes in the above bullet point:
[Cu2(L4)2] is removed because it appears to be the same as “[Cu2(L4)2]” which is printed right after;
The “2” between “(L5)” and “(H2O)” in “[Cu2(L5)2(H2O)]·2H2O” should be in subscript as shown above;
The “2” between “(L6)” and “(H2O)” in [Cu2(L6)2(H2O)]·2H2O should be in subscript as shown above;
In claim 15, there should be a period at the end of the sentence (i.e., a period after the structure of H2L6).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 9-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Prior art referenced:
Slator et al. (Slator) (Slator, C. et al. Di-copper metallodrugs promote NCI-60 chemotherapy via singlet oxygen and superoxide production with tandem TA/TA and AT/AT oligonucleotide discrimination. Nucleic Acids Research 2018, pg. 1-18).
The claims are broad insofar as the instant claims recite a method for treating any cancer, wherein the method comprises administering to a subject a therapeutically effective amount of a phenoxido copper compound as recited in instant claim 9.
Although the claims are broad, the instant specification provides limited working examples:
In vitro cytotoxicity against human cell lines (starts on para. 000107)
Wherein the cancer cell lines include:
A2780: ovarian carcinoma
A2780R: cisplatin-resistant ovarian carcinoma
PC-3: prostate adenocarcinoma
22Rv1: prostate carcinoma
MCF-7: breast adenocarcinoma
HOS: osteosarcoma
A549: lung adenocarcinoma
PANC-1: pancreatic epithelioid carcinoma
CaCo2: colorectal adenocarcinoma
HeLa: cervical carcinoma
Only complex 6 was tested against all the cancer cell lines (except for 22Rv1 cell line; see Figure 9 for in vitro cytotoxicity data)
Complexes 1-5 and 7 were tested against at least three cancer cell lines (see Figure 9 for in vitro cytotoxicity data).
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
The prior art further demonstrates that cytotoxicity of Cu(II) complexes was not predictably shared across all cancer cell lines. For example, Slator evaluated the dinuclear Cu(II) complexes, Cu-Oda and Cu-Terph (see Figure 1A for general structure), against the NCI-60 panel (which includes breast, colon, central-nervous-system, leukemia, non-small-cell lung, melanoma, ovarian, prostate, and renal cancer cell lines) (see pg. 6, left col., “Results and Discussion” section, 1st paragraph). Although Cu-Terph exhibited enhanced cytotoxic effects across the majority of cell lines within the panel and Cu-Oda was particularly effective against melanoma, renal, and prostate cancer cells, Slator explicitly reports that leukemia cell lines were resistant to both of the Cu(II) complexes (see pg. 6, right col., 1st paragraph). Thus, the art demonstrates that activity of a Cu(II) complex against several cancer types does not predict activity against all cancer types (which also includes many other cancer types not included in the NCI-60 panel tested in the prior art).
Accordingly, the disclosed activity of one complex (i.e., complex 6) against 9 selected cancer cell lines, together with the more limited testing of complexes 1-5 and 7 against at least 3 cancer cell lines (wherein 2 of the 3 are ovarian cancer cell lines), does not adequately represent the full diversity encompassed by “cancer.” The specification, therefore, fails to provide:
a representative number of embodiments reflecting the full scope of “cancer” within the claimed method genus.
Therefore, a POSITA would not reasonably conclude from the disclosure that the inventors were in possession of the full scope of instant claims 9-16 as of the effective filing date.
Claim Rejections - 35 USC § 112(b)
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 2-8 and 10-16 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.
Claims 2-8 recite: “wherein L is a ligand…” Claims 2-8 are dependent on claim 1. Claim 1 does not recite the limitation “L.” Claim 1 only recites the following limitations: L1, L2, L3, L4, L5, L6, and L7. Therefore, there is insufficient antecedent basis for the limitation, “L,” in claims 2-8.
Claims 10-16 recite: “wherein L is a ligand…” Claims 10-16 are dependent on claim 9. Claim 9 does not recite the limitation “L.” Claim 9 only recites the following limitations: L1, L2, L3, L4, L5, L6, and L7. Therefore, there is insufficient antecedent basis for the limitation, “L,” in claims 10-16.
Note on 35 USC § 102 and § 103 Rejections
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Furthermore, in the 35 USC § 102 and § 103 Rejections discussed below, the following art is cited:
Massoud et al. (Massoud) (Massoud, S. S. et al. Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents. European Journal Of Medicinal Chemistry 2023, 246, 114992.; published online December 5, 2022.).
The invention disclosed in the instant specification is essentially disclosed in the Massoud NPL as well.
Although Massoud is identified as a co-author of the NPL, the publication also identifies authors who are not named as inventors in the instant application. Massoud’s co-authorship alone does not establish that the relevant subject matter disclosed in the instant application originated with Massoud.
According to MPEP § 2153.01(a):
The Office has provided a mechanism for filing an affidavit or declaration (under 37 CFR 1.130 ) to establish that a disclosure is not prior art under AIA 35 U.S.C. 102(a) due to an exception in AIA 35 U.S.C. 102(b). See MPEP § 717. In the situations in which it is not apparent from the grace period disclosure itself or the patent application specification that the disclosure is an inventor-originated disclosure, the applicant may establish that the AIA 35 U.S.C. 102(b)(1)(A) exception applies by way of an affidavit or declaration under 37 CFR 1.130(a). MPEP § 2155.01 discusses the use of affidavits or declarations to show that a disclosure was an inventor-originated disclosure made during the grace period.
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.
Rejection Part 1:
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Massoud et al. (Massoud) (Massoud, S. S. et al. Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents. European Journal Of Medicinal Chemistry 2023, 246, 114992.; published online December 5, 2022.).
Massoud discloses the following compounds:
shiny green-olive or green dinuclear doubly bridged-phenoxido-copper(II) complexes [Cu2(L1-2)2](ClO4)2 (1, 2), [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) (see pg. 2, right col., paragraph before the “2.2. characterization of the compounds” section, 1st sentence) and
an intense purple 1D polymeric, catena-[Cu(L7)] (7) (see see pg. 2, right col., paragraph before the “2.2. characterization of the compounds” section, 2nd sentence)
wherein the structures of L1-7 are:
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343
706
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, respectively (see pg. 2, scheme 1).
Note: complexes 1-7 disclosed in Massoud are the same as complexes 1-7 disclosed in the instant application and are encompassed by instant claims 1-8.
Therefore, Massoud anticipates instant claims 1-8.
Rejection Part 2:
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Michel et al. (Michel) (Michel, F. et al. An Unprecedented Bridging Phenoxyl Radical in Dicopper(II) Complexes: Evidence for an S = 3/2 Spin State. Angew. Chem. Int. Ed. 2005, 44, 438-441.)
Michel discloses [L’Cu]22+ as its ClO4- salt (see Michel, pg. 439, left col., 11th line from the bottom and Figure 1). The ligand, L’, has the following structure:
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214
220
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(see Michel, pg. 439, left col.).
This Cu(II) complex disclosed by Michel is encompassed by instant claims 1 and 2 wherein:
the phenoxido copper complex has the following chemical structure: [Cu2(L1)2](ClO4)2 and
the ligand is:
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199
292
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.
Therefore, Michel anticipates instant claims 1 and 2.
Rejection Part 3:
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Mijanuddin et al. (Mijanuddin) (Mijanuddin, M. et al. Concomitant polymorphism of an antiferromagnetically coupled dicopper(II,II) complex with single strand helical assembly: Synthesis, structure, DSC, magnetic and heterogeneous catalytic studies. Polyhedron 2009, 665-672.)
Mijanuddin discloses a [Cu2(L)2] complex (see Mijanuddin, Fig. 2) wherein the ligand, L, has the following structure:
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167
248
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(see Mijanuddin, pg. 666, left col.).
This Cu(II) complex disclosed by Mijanuddin is encompassed by instant claims 1 and 5 wherein:
the phenoxido copper complex has the following chemical structure: [Cu2(L4)2] and
the ligand is:
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220
218
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.
Therefore, Mijanuddin anticipates instant claims 1 and 5.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
Massoud et al. (Massoud) (Massoud, S. S. et al. Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents. European Journal Of Medicinal Chemistry 2023, 246, 114992.; published online December 5, 2022.).
The teachings of Massoud as they apply to claims 1-8 are as discussed in the “Claim Rejections - 35 USC § 102” section above and are incorporated herein.
Given that instant claims 1-8 are anticipated by Massoud, a POSITA would have also found it obvious to reproduce the subject matter disclosed.
Therefore, instant claims 1-8 are rendered obvious.
Massoud further discloses the following (see pg. 2, left col., last paragraph):
The synthesis and characterization of the 7 Cu(II) complexes as well as their anticancer activity against human cancer cells was the main target for the study.
The in vitro cytotoxicity of the synthesized bridged-phenoxido-copper(II) compounds 1–6, the 1D polymeric complex 7, and their parent free ligands were tested against selected human cancer cell lines as well as MRC-5 normal cells.
To clarify the mechanistic pathways of these complexes different biological approaches were conducted on the best performing cytotoxic complexes (4, 6 and 7) in order to understand their influence on the cellular cycle and cell modification of A2780.
Massoud does not explicitly disclose administering the complexes to a subject to treat ovarian cancer.
Nevertheless, a POSITA would still have found it prima facie obvious before the effective filing date of the claimed invention to administer one of Massoud’s phenoxido copper(II) complexes to a subject with ovarian cancer in a therapeutically effective amount. A POSITA would have been motivated to do this because Massoud explicitly identifies complexes 1-7 as anticancer agents (see Massoud, title) and demonstrates that the complexes are cytotoxic against both A2780 and A2780R ovarian cancer cell lines (see Table 2). Massoud’s additional findings that selected complexes affect the cell cycle and induce cell-death pathways in A2780 cells (see pg. 6, section “2.8 Cell death induction in the A2780 cells”) would have further supported the use of complexes 1-7 against ovarian cancer.
As such, instant claims 9-20 are also rendered obvious.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H. MURRAY can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
