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 .
Status of the Claims
Claims 1-20 are pending. Claims 1-20 are rejected.
Information Disclosure Statement
The information disclosure statement (IDS) dated 08/15/2023 has been considered.
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.
Claims 5-9 and 16-18 are rejected under 35 U.S.C. 112(b) being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claim 5, the claim recites “the first ovarian cancer cell line resistant to cisplatin, A2780cis, to a half maximal inhibitory concentration in the first ovarian cancer cell line, A2780” (emphasis added). However, there is no previous mention in claim 1 of a first ovarian cancer cell line for either cell type. There is insufficient antecedent basis for these “the first” limitations in the claim. Applicant may overcome the rejection by, for example, amending the claim from “the first” to “a first” in both instances.
Regarding claims 6-8, each claim also recites “the first” as indicated in the rejection of claim 5 above. See lines 5, 8, 11 and 13. Since there is no mention in claims 1 or 2 of a first ovarian cancer cell line, there is insufficient antecedent basis for this limitation in the claim. Applicant may overcome the rejection by, for example, amending the claim from “the first” to “a first” in each instance.
Regarding claim 9, the claim recites a “second ovarian cancer cell line, SKOV3”, however there is no mention of a first ovarian cancer cell line in the claim itself or claims 2 or 1 from which it depends. There is insufficient antecedent basis for this limitation in the claim. Applicant may overcome the rejection by, for example, amending claim 9 so that it depends from claim 3 instead of claim 2.
Regarding claims 16-18, each claim recites “the sample”. See lines 5, 7, 10, 12, 15 and 17. There is insufficient antecedent basis for this limitation in the claim. It is unclear which of the samples of claim 12 are being referred to in dependent claims 16, 17 and 18. Applicant may overcome the rejection by, for example, specifically stating which sample, either the monolayer of cells, a multicellular tumor spheroid, or an in vivo xenograft tumor, is intended in each claim.
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.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sulaiman, A. et al. "Design, Synthesis, and Preclinical Activity in Ovarian Cancer Models of New Phosphanegold(I)-N-heterocyclic Carbene Complexes" J. Med. Chem. 2022, 65, 14424-14440.
Sulaiman et al. teach seven gold(I) complexes with structures identical to the seven described in the instant claims and specification, including complex 6:
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(see Scheme 1 on page 14425) which is embraced by the instant claims wherein the phosphane ligand is tricyclohexylphosphane, per claim 2. Thus claims 1 and 2 are anticipated by the prior art.
The properties of half maximal inhibitory concentration in ovarian cancer cell line A2780 (per claims 3 and 6) and the cisplatin-resistant A2780cis (per claims 4 and 7) are also taught by Sulaiman et al. Per the reference, complex 6 has an IC50 of 0.14 uM and 0.12 uM in A2780 and A2780cis cell lines, respectively. See Table 2 on page 14427 which is reproduced here:
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. In the same table, the prior art shows that complex 6 has a fold resistance of 0.86 based on a ratio of these IC50 values, which is within the range of 0.5 to 2 recited in claim 5 and a range of less than 1 recited in claim 8. Thus claims 3-8 are anticipated by the prior art.
Regarding instant claim 9, Sulaiman et al. teach that complex 6 inhibited SKOV3 cells with an IC50 value of 0.58 uM, see page 14427, second column, second paragraph:
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. This value is within the range of 0.55 to 0.65 uM recited in claim 9. Thus claim 9 is anticipated by the prior art.
Regarding instant claim 10, drawn to a pharmaceutical composition comprising the complex of claim 1 and at least one pharmaceutical additive or adjuvant, Sulaiman et al. describe, a cell viability assay using MTT as an additive. See page 14436, right column, “Cell Viability Assay” section, first paragraph:
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. Thus, claim 10 is anticipated by the prior art.
Regarding instant claim 11, which is interpreted as a product-by-process claim, according to MPEP 2113 I, the patentability of such claims must be determined by the structure: “‘[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.’ In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” Thus, claim 11 is anticipated by the prior art.
Regarding claim 12, Sulaiman et al. teach experiments wherein complex 6 was administered in vitro to a monolayer of SKOV3 cells (see page 14437, left column, “Wound Healing Assay and Cytoskeleton Organization” section), to SKOV3-MCTSs (see page 14436 right column, “SKOV3-MCTSs” section) and in vivo to mice with SKOV3-Xenografts (see page 14434, right column, “Effects of Complex 6 in SKOV3-Xenografts Growth”). Thus, claim 12 is anticipated by the prior art.
Regarding claim 13, Sulaiman et al. teach that complex 6 was able to induce apoptosis in A2780 and A2780cis cells (see page 14427, right column, fifth paragraph and Figure 3A on page 14429) and SKOV3-MCTSs (see page 14428, left column, second paragraph and Figure 4D on page 14430). Sulaiman et al. also state “Complex 6 induced apoptosis… not only in A2780 and A2780cis but also in the 3D-SKOV3-MCTSs” in the second paragraph of the Conclusion section on page 14435. Thus, claim 13 is anticipated by the prior art.
Regarding claim 14, Sulaiman et al. display results of the experiment wherein complex 6 decreased the volume of SKOV3-MCTSs by approximately 85 to 95% based on volume after 7 days of treatment at a concentration of 1 uM in Figure 4A on page 14430:
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. On page 14428, left column, first paragraph, Sulaiman et al. state: “At the concentration of 1 uM, complex 6 almost completely destroyed SKOV3-MCTSs (Figure 4A,B).” It is clear in the figure that the T=7 days group at 1 uM concentration shows a volume of approximately 10%. Thus, claim 14 is anticipated by the prior art.
Regarding claim 15, Sulaiman et al. display results of the experiment wherein complex 6 generates mitochondrial reactive oxygen species in SKOV3-MCTSs of 50 to 60% based on cell count 24 hours after administration at a concentration of 0.50 uM in Figure 4G and 4H on page 14430:
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and
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. Thus, claim 15 is anticipated by the prior art.
Regarding claims 16 and 17, Sulaiman et al. display results of the experiments wherein complex 6 was administered to samples at a concentration of either 0.15 uM or 0.50 uM and those samples exhibited a change in the amount of cells in the S phase and G1 phase after 24 hours in Figure 5A on page 14431:
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. Since the SKOV3 test, for example, had an amount of S phase cells of about 20% at 0.5 uM compared with about 40% in medium, claim 16 is anticipated by the prior art. Since the SKOV3 test, for example, had an amount of G1 phase cells of about 70% at 0.15 uM compared with about 50% in medium, claim 17 is anticipated by the prior art.
Regarding claim 18, Sulaiman et al. display results of the experiment wherein complex 6 decreases proteasome activity by about 70% after 24 hours based on a 20S-proteasome assay after being administered at a concentration of 0.5 uM in Figure 5D on page 14431:
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. The section “Thioredoxin Reductase and 20S Proteasome Activity” in the left column on page 14437 indicates that the results of this experiment were obtained 24 hours after treatment:
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. Thus, claim 18 is anticipated by the prior art.
Regarding claim 19, Sulaiman et al. display results of the experiment wherein complex 6 decreased xenograft tumor volume and weight by more than 80% compared with vehicle after being administered 2 mg/kg of the complex twice a week for 35 days in Figure 8 on page 14434:
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. Thus, claim 19 is anticipated by the prior art.
Regarding claim 20, drawn to a pharmaceutical composition comprising the complex of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient, Sulaiman et al. describe, for example, a cell viability assay in which cells were treated with 0-1uM concentrations of the gold complexes. See page 14436, right column, “Cell Viability Assay” section. A person having ordinary skill in the art would expect that the carrier used to dissolve the gold complexes was pharmaceutically acceptable. Thus, claim 20 is anticipated by the prior art.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jalisa H. Ferguson whose telephone number is (703)756-1489. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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/J.H.F./Examiner, Art Unit 1626
/JOSEPH K MCKANE/Supervisory Patent Examiner, Art Unit 1626