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 .
Filing Receipt and Priority
The filing receipt mailed 06/6/2025 states that the instant application is a 371 of PCT/EP2022/087023, filed 12/20/2022.
The filing receipt also states that the instant application claims foreign benefit of EPO 21306878.6, filed 12/21/2021.
Information Disclosure Statement
The information disclosure statement filed 06/11/2024 has been considered.
Restriction/Species Election
Applicant’s election without traverse of Group I, claims 1-10 is acknowledged. Applicant’s election of AM23 as the iron metabolism disruptor and uveal melanoma is also acknowledged.
At examiner’s discretion, search and examination has been broadened to include salinomycin.
Objection
Claim 5 claims administration of either salinomycin or its derivative, AM23.
Claim 6 claims administration of ironomycin.
The specification on p. 5, l. 26 states “Ironomycin also called as AM5 or AM23…”.
While applicant is their own lexicographer, the claims would be in better form if applicant were to use one name for the compound ironomycin. Either ironomycin or AM23 is appropriate.
Rejections
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.
Claim(s) 1-2 and 4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou (Molecular Cancer, 2019, 18:159, of the record).
Zhou in p. 4, Fig. 2 description discloses that “Salinomycin elicits apoptosis in UM cells.” Additionally, Zhou on p. 7, Fig. 4 states “Salinomycin suppresses outgrowth of Xenografted UM cells in NOD/SCID mice.” Zhou on p. 8, sec. Xenografted Experiments states “Three million of Omm1 cells were subcutaneously injected into the flanks of 4- to 6-week male NOD/SCID mice.
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.
KSR Rationales
The MPEP in section 2143, subsection I gives examples of Rationales for supporting a conclusion of obvious. These rationales are non-exhaustive and include (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claim(s) 1-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (cited above).
Discussion of Zhou from the 102 rejection above is incorporated here.
Regarding claim 3, Zhou on p. 2, Fig. 1 teaches administration of salinomycin to uveal melanoma cell line Omm2.3 (also known as Omm1.3). While the specification does not explicitly state which uveal melanoma cell lines are resistant uveal melanoma, the cell lines which salinomycin was tested against are OMM1.3, MM28, MP46, MP65 (p. 24, sec. Figure 2). Additionally, the specification on p. 25, sec. Figure 6 and Figure 7 indicates that the OMM1.3 cell line is a metastatic cell line. One of ordinary skill would find it obvious to administer salinomycin to a patient with resistant uveal melanoma as the cell line taught by Zhou is one that was tested against in the instant application.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill to administer salinomycin to treat uveal melanoma resistant with a reasonable assumption of success. One of ordinary skill would find motivation to practice the method of administering as the art teaches salinomycin has efficacy in killing uveal melanoma cells.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (cited above) as applied to claims 1-4 above, and further in view of Versini (Chem. Eur. J. 2020, 26, 7416-7424), Chen (OncoTargets and Therapy, 2020:13 12243-12252), Branisteanu (Experimental and Therapeutic Medicine, 22: 1428, 2021, published online 10/11/2021) and Manjandavida (Indian J. Opthalmol. 2015; 63(2):141-145).
Regarding claims 1-4, discussion of Zhou from the 102 and 103 rejections above is incorporated here.
Zhou on p. 13, sec. Salinomycin decreases cancer stem-like cells in UM teaches that salinomycin is a selective inhibitor of cancer stems cells and that “salinomycin is active against CSCs in UM cells.”
Zhou does not discuss ironomycin, administration methods, or the combination with a classical melanoma treatment. This is addressed by the combination of Versini, Chen, Branisteanu, and Manjandavida.
Regarding claims 5 and 6, Versini on p. 7417, left col., para. 2 states “We have previously reported solid evidence that [Salinomycin] and its synthetic derivatives –in particular ironomycin (2) – kill [cancer stem cells] by sequestering iron in lysosomes…”.
Chen on p. 12249, left col., para 1 states “It was found that salinomycin could eliminate UM-CSC in the mouse model of UM liver metastasis and effectively inhibit liver metastasis, they believed that Twist1 was the basis of salinomycin-induced clearance of CSCs and inhibition of UM cell migration and invasion.” Additionally, Versini in its abstract states “It has bene previously shown that salinomycin and its C20-propargylamine derivative (Ironomycin (2)) accumulate in lysosomes and sequester iron in this organelle.”
Considering the evidence provided in Versini, that ironomycin works similarly to salinomycin in affecting cancer stem cells, and the teachings of Chen, which indicate that uveal melanoma is affected by cancer stem cells in uveal melanoma are affected by salinomycin, one of ordinary skill in the art would find it obvious to replace salinomycin with ironomycin as the two compounds have the same mechanism of action.
Regarding claims 8-10, Breanisteanu, on p. 5, sec. Treatments for metastatic disease states “The usage of systemic chemotherapy has offered poor results suggesting that uveal melanoma is resistant to current chemotherapies. Conventional drugs (dacarbazine, temozolomide, docosahexaenoic acid, and liposomal vincristine) have offered discouraging results, in monotherapy and also in combination. The most encouraging data have been noted with the combination of treosulfan and gemcitabine that showed a median survival of 14 months and an annual survival rate of 80%.”
The art indicates that chemotherapy in combination can have limited efficacy. However, the art also teaches that certain compounds have had some efficacy. The MPEP section 2144.06 states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
Therefore, one of ordinary skill would find it obvious to combine salinomycin and/or ironomycin with a classical melanoma treatment agent shown to be effective.
Regarding claim 7, Manjandavida in its abstract teaches intravitreal application of chemotherapy medication where it states “Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide.”
This teachings indicates that intravitreal administration of chemotherapeutic drugs is known within the art. Additionally, formulating a drug for topical and/or intravitreal application is within the skillset of one of ordinary skill in the art.
The prior art teaches administration of salinomycin to treat uveal melanoma in xenografted mice. The art further teaches the mechanism of salinomycin, of killing cancer stem cells in uveal melanoma, is shared with ironomycin. Classical methods of treating uveal melanoma are known within the art as well as intravitreal administration.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Zhou, Versini, Chen, Branisteanu, and Manjandavida to arrive at the instant claims with a reasonable assumption of success. One of ordinary skill would be motivated to make the combination because the art teaches ironomycin has similar efficacy to salinomycin and because it would be obvious to combine classical methods of treating uveal melanoma with administration of salinomycin and/or ironomycin.
Conclusion
No claims allowed.
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/LUISALBERTO GONZALEZ/Examiner, Art Unit 1624
