DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 08/24/2023, is acknowledged.
3. Claims 2, 5, 7-10, 13-16, 18-20, 22-24, 28 are pending and under examination.
4. Applicant’s IDS, filed 08/24/2023, is acknowledged.
5. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(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.
6. Claims 14-15, 20, 24 and 28 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
The recitation "preferably ..." in claims 14-15, 20, 24 and 28 is indefinite because the narrow range within the broad range using the term “preferably” renders the claim indefinite.
7. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
8. Claim 28 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 28 encompasses methods of “preventing” and treating a broad genus cancer or tumor in human subject with the claimed anti-CD73 antibodies.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification on page 1 under Background of the Invention discloses that CD73 is highly expressed in different tumor cells such as breast cancer and lung cancer, and the high expression of CD73 is positively correlated with poor prognosis. Yet, the claims are directed to the treatment of each and every cancer or tumor with anti-CD73 antibdy.
The specification under Example 4 discloses that anti-CD73 antibodies of the invention bind to human CD73 overexpressed on CHO- S cells.
The specification under Example 7 discloses the anti-tumor activity of the anti-CD73 antibodies using NOG mice inoculated with breast cancer cell line MDA-MB-231. The results of tumor inhibition rate are shown in Fig. 11 and Table 4.
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The specification under Example 8 discloses the anti-tumor efficacy of the anti-CD73 antibody of the present invention combination with an anti-PD-1 antibody in an A375 tumor-bearing humanized mouse model. In particular, mice were subcutaneously inoculated with A375 human malignant melanoma cell into the right abdominal region of NOG mice. The drugs were administered on days 1, 4, 8, and 11 after inoculation as shown in Table 5. The results of tumor inhibition rate are shown in Figure 13 and Table 5: The tumor inhibition rate in the ADI-37505 treatment group is 33%, and the tumor inhibition rate of the combination therapy of ADI-37505 and PD-1 antibody (sintilimab) is 61%, which is significantly excellent than that of each single drug.
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The specification discloses only two cancer species melanoma and breast cancer treatment with the claimed anti-CD73 antibodies, while the claims are directed to the prevention and /or treatment of a broad genus of cancers and tumors in human subject.
The specification fails to show that all cancers and tumor overexpress CD73, which is responsible for the generation f immune suppressive adenosine and thus would be a target for the treatment with the claimed anti-CD73 antibodies.
If the use disclosed is of such nature that the art is unaware of successful treatments with chemically analogous compounds, a more complete statement of how to use must be supplied.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988).
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the 'inventor' would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
The MPEP states that the issue of "correlation" is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
Importantly, the burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to cancer and /or tumor within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti-CD73 antibody in preventing cancer/tumor state. For example, the specification discloses that the inoculated NOG mice were first injected with anti-CD73 antibody after inoculation. (e.g. see Examples 8-9 of the instant specification). The specification does not show that anti-CD73 antibody being injected prior to melanoma/breast cancer inoculation. Therefore, the specification at most discloses a method of treating CD73 overexpressing cancer by administering the anti-CD73 antibody but not preventing cancer/tumor in human subject.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
9. Claims 2, 5, 7-10, 13, 16, 18-19, 22-23 are free form prior art and are allowable.
10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kurago et al. Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy. Front. Immunol. 14:1212209, 2023.
Kurago et al teach approximately 50 active phase I/II cancer immunotherapy trials targeting the CD73-AR IC are listed on https://clinicaltrials.gov. Among these, more than 60% were designed to target CD73 by monoclonal antibodies or small molecule inhibitors, some of which were combined with PD-1/PD-L1 ICB regimens. The other 30-40% have employed small molecule inhibitors targeting A2AR alone or together with anti-CD73 and/or A2BR inhibitors (8, 61, 83–86). In addition to the safety (severity of adverse event, AE) and pharmacokinetic assessment of the therapeutic agents, a secondary objective was to collect data on clinical benefit rate (CBR), consisting of complete response (CR), partial response (PR) and stable disease (SD). Also, progression-free survival (PFS), objective response (OR), overall response rates (ORR) and overall survival (OS) were assessed based on standardized Response Evaluation Criteria in Solid Tumors version 1.1 (82) (for details, see legend to Table 1) (section 4).
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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August 1, 2025
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644