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 .
Receipt of claim amendments filed on 05/01/2026 is acknowledged. Claims 1 and 9-11 have been canceled. Claims 2-8 and 12-20 are currently pending.
Priority
The instant application claims priority as follows:
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Response to Election/Restriction
Applicant’s election without traverse, of Group II, drawn to a method of treating cancer or inhibiting the growth of cancer cells comprising administering a compound of Formula I in combination with an additional therapeutic agent, in the reply filed on May 1, 2025 is acknowledged. The elections of species prembrozilumab as additional therapeutic agent, and liver cancer as cancer type are also acknowledged. Claims 2, 4-8 and 12-20 read on the elected species.
Examination
Examination will begin with the elected species. In accordance with MPEP 803.02, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious. If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush claim and claims to the elected species will be rejected, and claims to the nonelected species will be held withdrawn from further consideration. Should applicant, in response to a rejection of a Markush claim, overcome the rejection by amending the Markush claim to exclude the species anticipated or rendered obvious by the prior art, the amended Markush claim will be examined again. The examination will be extended to the extent necessary to determine patentability of the Markush claim. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species.
Pursuant to MPEP 803.02, the elected species of combination composition of OBI-3424 and prembrolizumab and liver cancer was searched and found unpatentable over the art as detailed below. Therefore, examination was stopped and art has been applied against the claims. During the search, an additional combination composition for treating leukemia was found. The uncovered subject matter has been presented in this Office action for the purpose of a compact prosecution.
Subject matter outside of the searched/examined scope 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 2-8 and 12-20 are the subject of this Office Action.
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) 2-3, 8 and 12-15 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Lock et al. (WO2019/062919-cited by applicant in the IDS of 10/25/2023).
The prior art teaches a method for treating leukemia comprising administering a compound of Formula I or Formula II
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in combination with other anti-cancer medicines and a pharmaceutically acceptable excipient. See whole document, particularly, paragraphs:
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and
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See also paragraph [0025], Experiment 6, Figure 17, for particular treatment with a combination of OBI-3424 and nelarabine.
The method treats leukemia that overexpresses ARK1C3, per at least paragraph [0026], examples and Figures.
Paragraph [0040] teaches effective amounts used:
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Paragraph [0044] teaches:
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See also prior art claims 15-18.
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.
Claims 2-8 and 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lock et al. (WO2019/062919-as above) and Duan (WO 2017/087428) and Oncology Times (40(23):p 73-80, December 5, 2018), in view of and Schmidt (JAMA Network Open. 2020; 3(2):e1920833), Chowdhury (Journal of Internal Medicine, 2018, 283; 110-120), or Longo (Medicina 2019, 55, 698) or Noonan (Expert Opinion on Investigational Drugs 2019, Vol. 28 (11) 941-949).
Applicant’s Invention
The present application is drawn to a method for treating cancer, such as the elected liver cancer, comprising administering a pharmaceutical composition comprising the compound of formula
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(known as OBI-3424, AST-3424, TH3424, Odafosfamide) and at least one additional therapeutic agent, such as an immune checkpoint inhibitor which is an anti-PD-1/PD-L1 antibody selected to be pembrolizumab.
Determination of the scope and content of the prior art (MPEP §2141.01)
The teachings of Lock et al. (WO2019/062919) were discussed above and are here incorporated by reference.
Duan
Duan discloses a method of treating cancer in a patient, and inhibiting the growth of cancer cells, wherein the cancer is a cancer wherein AKR1C3 reductase levels are high or higher than usual. The cancer is liver cancer, such as HCC, which overexpresses AKR1C3. The method comprises administering a composition comprising a compound of formula
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(known as OBI-3424, AST-3424, TH3424, Odafosfamide) and an excipient. See at least pages 2-3, paragraphs [0012], [0038], Figure 3, Examples 4 through 9 and claims 11-12. The compound was administered in effective amounts of 2.5 mg/kg and 5 mg/kg ([00127]).
Oncology Times
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The secondary references below show that the combinations of anticancer drugs with immune checkpoint inhibitors of PD-1 and PD-L1 have been found advantageous in the treatment of cancers.
Schmidt
Schmidt is drawn to PD-1 checkpoint inhibitor combination therapies reported in clinical trials. It disclosed that cancer drugs given in combination have the potential for increased tumor-cell killing, and finding the best combination partners for programmed cell death 1 (PD-1) checkpoint inhibitors could improve clinical outcomes for patients with cancer. The reference showed effective combinations with pembrolizumab. Schmidt disclosed that most combination trials showed the expected benefit of combining 2 active anticancer agents, while few combinations showed synergy according to the Bliss model. In addition,
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Chowdhury
Chowdhory taught combination therapy strategies for improving PD-1 blockade efficiency in cancer immunotherapy. “The key to improve the PD-blockade therapy is the development of combination therapies.” For example, pembrolizumab combined with chemotherapy enhanced the efficacy of chemotherapy alone (p. 113). See also the summary.
Longo
Longo is drawn to the use of immune checkpoint inhibitors against PD-L1/PD1 combined with other drugs for the treatment of hepatocellular carcinoma (HCC). It teaches prembrolizumab as an immune check point inhibitor in HCC. See at least abstract, table and figure 1.
Noonan
Noonan is drawn to recent clinical trials for the treatment of hepatocellular cancer. They disclose that “HCC results from aberrations in intracellular signaling and immune system dysregulation. Thus, a multisystem approach will be required to deliver personalized therapy. Combination therapies are likely to be future options.” See abstract. Noonan reported that pembrolizumab in combination with other anticancer agents is undergoing clinical trials for the treatment of HCC. See Table 1 and 2, and section 3.9. Noonan also reported on OBI3424 at page 947:
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Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
The prior art did not use a combination of OBI-3424 and pembrolizumab as immune checkpoint inhibitor anti-PD-1/PD-L1 antibody.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness 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.
Applying KSR exemplary rationale (A), it would have been prima facie obvious to administer a combination of OBI-3424 and pembrolizumab (Keytruda®) to treat patients with hepatocellular cancer in which AKR1C3 is overexpressed. Each agent was taught in the prior art for treatment of hepatocellular cancer, particularly, OBI-3424 at effective amounts was taught for treating hepatocellular cancer in which AKR1C3 is overexpressed, and each agent was also shown efficacious in combination with different chemotherapy drugs.
It has been held that “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).
Moreover, since the artisan knew that alkylating agents are immunosuppressive, the artisan would have been motivated to enhance the immune response to the cancer by integrating the immune-based therapy of a PD-1/PD-L1 inhibitor, as above. (At least Colvin (Alkylating agents. In:Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003-Section: Immunosuppression).
In view of the disclosure of the secondary references, a person having ordinary skill would have reasonably expected that the combination involving the claimed alkylating agent and the PD-1/PD-L1 immune checkpoint inhibitor pembrolizumab, would have resulted in a greater than expected response in comparison to administering either single agent alone.
In regards to claim 17, the limitation “that the combination acts corporately or synergistically to rescue a T cell inactivation and improve therapeutic efficacy” is not considered to further limit the treatment of claim 17 because it is merely a feature of the method that necessarily flows from administering the combination of OBI-3424 with an immune checkpoint inhibitor to patients having cancer, which is taught by the combination of references above.
Note MPEP 2112: The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103."The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983).
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004).
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.
Claim 12 is 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 12, the phrase “at least one therapeutic agent including a chemotherapeutic agent or biological agent” is ambiguous.
Claim 12 recites the broad recitation “at least one therapeutic agent”, and the claim also recites “including a chemotherapeutic agent or biological agent”, which appears to be the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claim 2 is 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 2 recites that the compound in the composition of claim 12 is of Formula I-1 or Formula I-2. This does not further limit the subject matter of claim 12 because Formula I-1 and Formula I-2 are the only compounds present in claim 12. 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.
Conclusion
Claims 2-8 and 12-20 are rejected.
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.
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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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