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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/27/2024 and 06/10/2024, are in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Priority
This U.S. Application filed on 03/27/2024, is a 371 of PCT/KR2022/014930, filed on 10/05/2022, which claims priority to KR Application No. 10-2021-0131698, filed on 10/05/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of the Claims
Claims 1-8 are pending.
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 1-2, 4-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Prevo et al (hereinafter “Prevo”, Cell Cycle, 2018, 17(12), 1513-1523) in view of Shin et al (hereinafter “Shin”, Cancer Cell, 2014, 26, 521-533).
By way of a background, the Applicants’ invention (see, e.g., page 1 of the specification), is directed to a method for treating bladder cancer with a combination therapy comprising an ID2 activator (ID2a), and a CDK inhibitor (CDKi). ID2 activation is mediated via activation of BMP (see, e.g., ¶s 110, 112 and 121 of the specification).
Independent claims 1 and 4 are directed to a method for treating or preventing bladder cancer, with a composition comprising a CDKi and an ID2a.
Similar to the Applicants’ invention (see discussions above), Prevo teaches a method for inhibiting the growth of bladder cancer cells (T24 tumor cell lines), with a composition comprising a Cdki (RO-3306, see abstract and Figure 1).
Prevo (see pages 1513-1514), discloses that: i) CDK inhibition can also be used in combination therapy; and ii) CDK inhibition can also act synergistically in a combination therapy. Accordingly, at the time of the instant invention, one skilled in the art would have understood that Prevo envisioned a method for treating bladder cancer with a CDKi (e.g., RO-3306), in a combination therapy. A person skilled in the art would have envisaged a method for treating bladder cancer with a CDKi (e.g., RO-3306), in a combination therapy in the disclosures of Prevo. One of the ordinary skills in the art would have had a reasonable expectation that the CDK inhibition would also act synergistically in the combination therapy.
Although Prevo is not explicit in teaching a CDKi in combination with an ID2a, the claimed invention would have been obvious over Prevo. This is because at the time of the instant invention, it was known in the art that an ID2a can be used for treating bladder cancer. For example, Shin teaches: i) mice models of bladder cancer with decreased ID2 expression compared to control mice without bladder cancer (see Figure S2); and ii) increase ID2 expression in treated bladder cancer mice compared to untreated bladder cancer mice (see Figure S4).
Shin relates to a method for treating bladder cancer with FK506 (a BMP activator, see abstract). Similar to the Applicants’ invention (see discussions above), Shin teaches ID2 activation mediated by a BMP activator (FK506, see Figure S4).
Accordingly, at the time of the instant invention, one skilled in the art would have envisaged a method for treating bladder cancer with a composition comprising a CDKi (e.g., RO-3306) and an ID2a (e.g., FK506), in the disclosures of Prevo and Shin.
A person of the ordinary skills in the art would have considered a combination therapy comprising a CDKi and an ID2a, in order to broaden the spectrum of therapeutic activity. One skilled in the art would have had a reasonable expectation that the CDK inhibition would also act synergistically in the combination therapy.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Therefore, claims 1 and 4 are obvious over Prevo and Shin.
Regarding claims 2 and 7, Prevo teaches RO-3306 (see discussions above).
Regarding claim 5, the claimed dosage form of administering the CDKi and ID2a as a mixed formulation or separate formulation, is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art.
MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
Claims 1-5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Prevo (Cell Cycle, 2018) in view of Shin (Cancer Cell, 2014), as applied to claims 1-2, 4-5 and 7 above and further in view of Beachy et al (hereinafter “Beachy”, U.S. Pub. No. 20170119740, published 05/04/2017).
The limitation of claims 1-2, 4-5 and 7 as well as the corresponding teachings of Prevo and shin are described above, and are hereby incorporated into the instant rejections.
The invention of claims 3 and 8 are similar to claims 1 and 4, however, claims 3 and 8 differ slightly from claims 1 and 4 in that claims 3 and 8 require, wherein the ID2a is selected from the group consisting of the list disclosed therein.
Although Prevo and Shin do not combine to disclose the ID2a of claims 3 and 8, the claimed inventions would have been obvious over Prevo and Shin. This is because at the time of the instant invention, an ID2a of claims 3 and 8, was known in the art. For example, similar to Shin (see discussions above), Beachy teaches an activator of BMP selected from the group consisting of FK506 (see abstract, ¶ 0049), isoliquiritigenin, 4-hydroxychalcone, apigenin and diosmetin (see ¶ 0059). Beachy discloses ID2 as a BMP responsive gene (see ¶ 0048). Beach also relates to use of BMP activator for treating cancer (see abstract) such as bladder cancer (see ¶ 0054). Similar to Shin (see pages 521 and 531), Beachy (see ¶s 0010-0023, Figures 1-13 and Example1), teaches treating mice models of BBN-induced bladder cancer with a BMP activator (FK506).
Accordingly, at the time of the instant invention, one skilled in the art would have envisaged a method for treating bladder cancer with a composition comprising a CDKi (e.g., RO-3306) and an ID2a of claims 3 and 8(e.g., apigenin), in the disclosures of Prevo, Shin and Beachy.
A person of the ordinary skills in the art would have considered a combination therapy comprising a CDKi and an ID2a, in order to broaden the spectrum of therapeutic activity. One skilled in the art would have had a reasonable expectation that the CDK inhibition would also act synergistically in the combination therapy.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
Claims 1-2,4-6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Prevo (Cell Cycle, 2018) in view of Shin (Cancer Cell, 2014), as applied to claims 1-2, 4-5 and 7 above and further in view of: 1) Lou et al (hereinafter “Lou”, U.S. Pub. No. 20190120844, published 04/25/2019); and 2) Kawahara et al (hereinafter “Kawahara”, Oncotarget, 2014, 6(3), 1582-1593).
The limitation of claims 1-2, 4-5 and 7 as well as the corresponding teachings of Prevo and shin are described above, and are hereby incorporated into the instant rejections.
The invention of claim 6 is similar to claim 4, however, claim 6 differs slightly from claim 4 in that claim 6 requires, wherein a dosage of the CDKi is 1 mg/kg to 10 mg/kg, and a dosage of the ID2a is 5 mg/kg to 150 mg/kg.
Although Prevo and Shin do not combine to disclose the dosage requirement of claim 6, the claimed inventions would have been obvious over Prevo and Shin. This is because the claimed dosage regime is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. For example:
1) Lou (see ¶s 0054-0055), discloses that an effective amount of a CDKi (e.g., RO-3306), can be from about 1 mg/kg to about 200 mg/kg. Effective doses can vary depending on the severity of the cancer, the route of administration, the age and general health condition of the subject, excipient usage, the possibility of co-usage with other therapeutic treatments such as use of other agents, and the judgment of the treating physician.
2) Kawahara discloses that bladder cancer can be treated with FK506 (an ID2a, see discussions above), at a dosage of 3mg/kg/day (see, e.g., page 1591 and Figure 1).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Accordingly, at the time of the instant invention, one skilled in the art would have envisaged a method for treating bladder cancer with a composition comprising a CDKi (e.g., RO-3306) and an ID2a (e.g., FK506), wherein the CDK dosage and ID2a dosage are within the dosage limitations of claim 6, in the disclosures of Prevo, Shin, Lou and Kawahara.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
Conclusion
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
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
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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