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 .
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.
Claims 3, 20, 24, 35, 41, and 43 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.
Regarding claims 3, 20, 24, 41, and 43, the term “at least about” is a relative term which renders the claim indefinite. The term “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, it is unclear exactly what the lower bound for the claimed ranges are in each of the claims containing “at least about”.
Regarding claim 35, applicant recites administration of the IL-27 antibody, atezolizumab, and bevacizumab “on the same day, concurrently, or sequentially”. The phrase “on the same day, concurrently, or sequentially” presents ambiguity because it is unclear whether “concurrently or sequentially” refers to the days of administration or the order in which the antibodies are to be administered. Accordingly, a person of ordinary skill in the art cannot determine the metes and bounds of the claim with reasonable certainty. To advance compact prosecution, the examiner is interpreting claim 35 to be “administered on the same day, either concurrently or sequentially.”
Therefore, claims 3, 20, 24, 35, 41, and 43 are rejected under 35 U.S.C. 112(b).
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 1-3, 5, 20, 21, 24, 25, 35, 40, 41, 43, and 45-52 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al (US 2019/0382474-A1), in view of Finn et al. (2020).
Claims 1-3, 5, 20, 21, 24, 25, 35, 40, 41, 43, and 45-52 are drawn to two methods: a method of stimulating an immune system and a method of treating a cancer, both methods comprise administering an antibody, comprising specific heavy and light chains, that bind human IL-27, and coadministration of the drugs atezolizumab and bevacizumab.
Regarding claims 1 and 2, Hill discloses an antibody that binds human IL-27 comprising heavy and light chains of SEQ ID NOs 177 and 69 of Hill’s sequence listing (specification, page 16 paragraph 2). These sequences comprise the CDRs of instant claims 1 and 2 (instant SEQ ID NOs 5-7 and 13-15), and the further structural limitations of instant claims 41, 43, 45, 46, 48, and 49 (instant SEQ ID NOs: 11, 19, 11 and 19, 21, 23, 21 and 23). Hill also discloses an antibody comprising the heavy and light chains of SEQ ID NOs 181 and 69 of Hill’s sequence listing (specification, page 16 paragraph 4). These sequences correspond to instant claims 47 and 50 (instant SEQ ID NOs: 25, 25 and 23). Further, Hill teaches that IL-27 attenuation via an antibody can reduce PD-L1 expression, thereby inducing an immune response and treating cancer (specification; page 21, paragraph 5) (Instant claims 1 and 2). Hill discloses a method of treating cancer in a subject comprising the IL-27 antibody and either atezolizumab (specification, page 23 paragraph 1) or bevacizumab (specification, page 103 paragraph 2). The cancer may be hepatocellular carcinoma (specification, page 22 paragraph 2) (instant claim 52).
However, Hill does not teach coadministration with both atezolizumab and bevacizumab.
Finn teaches a method of treating hepatocellular carcinoma comprising administering a combination of atezolizumab and bevacizumab to human subjects (instant claims 1, 2, 51, 52). Finn specifically teaches administration of atezolizumab at a dose of 1200 mg (instant claim 20) once every three weeks (instant claim 21), and bevacizumab at a dose of 15 mg/kg (instant claim 24) once every three weeks (instant claim 25), and potentially administered together on the same day (instant claim 35). While Finn does not teach administration on different days (instant claim 40), this would have constituted routine optimization in the art at the time.
Although neither Hill nor Finn teaches the combination of an IL-27 antibody, atezolizumab, and bevacizumab as a combination therapy, one of ordinary skill in the art would have been motivated to combine IL-27 antagonism with PD-L1 and VEGF inhibition to target multiple non-redundant mechanisms of tumor-mediated immune suppression. As noted above, Hill teaches that IL-27 attenuation via an antibody can reduce PD-L1 expression, thereby inducing an immune response and treating cancer (specification; page 21, paragraph 5). Finn teaches PD-L1 inhibition with atezolizumab to restore T-cell activity and VEGF inhibition with bevacizumab to improve immune cell access to tumors. Based on these teachings, a person of ordinary skill would have had a reasonable expectation that combining IL-27 antagonism with atezolizumab and bevacizumab would enhance anti-tumor immune responses. Moreover, at the time of the invention, the use of immunomodulatory antibodies in combination cancer therapies was well known and routine, and the effects of IL-27 blockade, PD-L1 inhibition, and VEGF blockage were predictable and complimentary. Similarly, it would have been obvious to optimize the dose and timeline of administration for the IL-27 antibody (instant claims 3 and 5), as this was routine for a person of ordinary skill in the art at the time.
Therefore, the method of the invention is obvious in view of what was known in the art at the time of fling, and claims 1-3, 5, 20, 21, 24, 25, 35, 40, 41, 43, and 45-52 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/T.D.J./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675