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 .
Notice: Examiner Reassignment
The present Application is reassigned to Examiner Robert M. Kelly. Please address future correspondence accordingly.
Applicant’s amendment and argument of 9/2/26 are entered.
Claims 30 and 35 are amended.
Claims 5-7, 10-13, 17-18 are canceled.
Claims 51-54 are newly added.
Claims 1, 30, 35, and 51-54 are pending and considered herein.
Claim Status, Canceled Claims
In light of the cancelation of Claims 5-7, 10-13, and 17-18, all rejections/objections thereto, are withdrawn.
Allowable Subject Matter
The previous examiner has made of record of reasons for allowability of Claim 1 and the present Examiner agrees to the same (See OA of 6/3/26, pp. 2-4).
Rejoinder
For clarity of record, it should be noted that the previous Examiner withdrew the restriction requirement between the restricted groups, and all methods of use under In re Ochiai have been rejoined.
Priority
This application is a 371 of PCT/US2020/055073 filed on October 9, 2020. Applicant’s claim for the benefit of a prior-filed application provisional application 62/913,655 filed on October 10, 2019 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
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.
In light of the amendments, the rejections of Claims 30, 51, and 53-54 are 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.
Claim 30 recites that the MYXV is administered at an MOI of between about 0.001 and 1000. Without stating what this multiplicity is with regard to, it is impossible to know what is meant. To wit, there is no leukocyte onto which it is adsorbed. Is this an MOI versus the total number of cells of the human? Is it MOI versus the number of cancer cells?
Claim 51 recites “the MYXV kills multiple myeloma cells”. It is not clear how a single MYXV kills multiple myeloma cells.
Claim 53 recites “at least about [a million] PBMC is adsorbed by being exposed to the MYXV”. It is not clear what is mean. What is adsorbed? Does this mean a million MYXV viruses are adsorbed onto a single PBMC or there are a total of a million adsorbed MYXV onto a the PBMCs? Or is the PBMC adsorbed onto something else, by exposure to the MYXV? Additionally, while being written as “adsorbed”, PBMCs are susceptible to infection by MYXV, and thus, they do not remain adsorbed, but are instead infecting the PBMCs. If they are not so-infected, the BiKE cannot be made. It is not clear what is being claimed.
Claim 54 recites “at least about [a million] PBMC is adsorbed by being exposed to the MYXV”. It is not clear what is mean. What is adsorbed? Does this mean a million MYXV viruses are adsorbed onto a single PBMC or there are a total of a million adsorbed MYXV onto a the PBMCs? Or is the PBMC adsorbed onto something else, by exposure to the MYXV? Additionally, while being written as “adsorbed”, PBMCs are susceptible to infection by MYXV, and thus, they do not remain adsorbed, but are instead infecting the PBMCs. If they are not so-infected, the BiKE cannot be made. It is not clear what is being claimed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 30 and 51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains 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.
Breadth of the Claims
Claim 30 recites “wherein the MYXV is administered at a multiplicity of infection … of between about 0.001 and 1000” and “the MYXV is administered systemically”. The claims are broad for the MOI as well as the breadth of systemic administration.
Nature of the Invention
The invention is in the nature of delivering gene therapy to treat myelomas, leukemias and lymphomas, to express a BiKE that targets NK/neutrophil cells and the cancer cells by way of CD16 and CD138, respectively, thereby bringing them together and allowing for destruction of the cancers (e.g., paragraph 5).
The State of the Prior Art
The prior art was relatively undeveloped at the time invention. To wit, while one similar mechanism of bringing immune cells together with cancer cells (e.g., Link, et al. (1998) “Anti-CD3-Based Bispecific Antibody Designed For Therapy of Human B-cell Malignancy Can Induce T-Cell Activation by Antigen-Dependent and Antigen-Independent Mechanisms”, International Journal of Cancer, 77: 251-56), these are associated with toxicity and are only performed at the level of protein therapy with the bispecific antibody (e.g., p. 251). Thus, from this, it is not predictable how much virus should be administered to affect the present therapy, as it requires determining how much of the protein would be made and secreted into the system to reach the target cells in high enough amounts to affect the attachment between the NK/neutrophil and cancer cell as claimed.
The level of skill in the Art
While the skill level is relatively high in the art, being that of PhD or MD, it is also clear from the art provided (e.g., SUPRA), that the Artisan still did not reasonably grasp the issue to affect a therapy reliably in a human.
The Level of Predictability in the Art
As shown above, the Artisan did not reasonably predict how much of a MYXY to add to get the particular multiplicity of invention for any particular cell type, much less that if so-adminsitered, that a produced BiKE would reach the target sites in high enough amount to affect a therapy.
The Amount of Direction provided in the Disclosure
At no point does the specification teach how to determine which cells in the body are to be counted to determine an MOI of administration. In fact, what it teaches, is that MOI is between the leukocytes and the MYXV exposed to the same, in vitro (e.g., paragraphs 5, 175-178, 184), prior to their administration.
In order to administer at a specific MOI, not only must you know which cells you are going to transfect in vivo, but you must know it will not infect a distinct cell type first. At the time of invention, it was known that myxoma virus infects, but is unable to replicate in human cells, save for tumor cells lacking components of the interferon system (e.g., Bell, et al. (2003) “Getting oncolytic virus therapies off the ground”, Cancer Cell, 4(1): 7-11, p. 8, paragraph bridging columns). Thus, it would not be known how much to add in any case, to target the correct cells, as all cells in the body act as depot for the virus, blocking their arrival at the site required for action. Additionally, with systemic administrations, first-pass organs are therefore most likely to capture the virus rather than reaching the target cell(s). For example, Oupicky, et al. (2002) “Importance of Lateral and Steric Stabilization of Polyelectrolyte Gene Delivery Vectors for Extended Systemic Circulation”, Molecular Therapy, 5(4): 463-72, ABSTRACT, teaches that the viruses are likely to be quickly eliminated by way of first pass organs.
Existence of working Examples
While there exist prophetic examples, the working examples consist of in vitro infected neutrophils/NK cells, which are then placed, in a test tube, with the cancer cells (e.g., Examples).
Quantity of Experimentation Needed
Given the likelihood of other cells intercepting the MYXV and first pass organ clearance, as well as a lack of target cells and their numbers in the body of the human being treated, and lack of targeting, the Artisan would have to experiment with the particular method of systemic treatment and amount of virus to administer, to transfect enough of the correct cell type, to obtain treatment.
This is considered undue experimentation as it amounts to such experimentation as is required to enable the invention for all of the claimed embodiments.
Note: Re allowability of Claim 35
It is noted that Claim 35 is limited to human subjects, PBMC, and adsorption of the MYXV, administered systemically and for myeolomas, lymphomas and leukemias. The composition (Claim 1) is a BiKE that binds to the CD138 and CD16, necessarily making it clear that the NK/neutrophils of the PBMC are the important component, and it is known as in the prosecution herein, that the CD138 binds to the myeloma/lymphoma/leukemia. Further, the prior enablement rejections which are not directly addressed above focus on solid cancers, which are necessarily removed by way of amendment. Link, et al. (1998) “Anti-CD3-Based Bispecific Antibody Designed For Therapy of Human B-cell Malignancy Can Induce T-Cell Activation by Antigen-Dependent and Antigen-Independent Mechanisms”, International Journal of Cancer, 77: 251-56 teaches a bispecific engager for T cells and cancerous B cells, which parallels the present mechanisms. Backed by the demonstration in vitro and models in the present examples, it is hard to argue that at least some of the blood-borne cancers in each of the claimed cancers would be treated by such systemic administrations of the PBMC so-infected by MYXV (it is argued that adsorbtion necessarily yields infected PBMC, as it is simply the first step). Thus, present Claim 35 is found enabled contrary to the previous rejections.
Conclusion
Claims 1, 35, 52-54 are allowed.
Claims 30 and 51 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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, Tracy Vivlemore can be reached at 571-272-2914. 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.
ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
Prosecution Insights