DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 30, 2026 has been entered.
Claims 3, 5, 6, 8, and 12-18 have been canceled.
Claims 1, 2, 4, 7, 9-11 and 19 have been amended.
Claim 20 has been added.
Claims 1, 2, 4, 7, 9-11, 19, and 20 are pending in the instant application.
Claims 1, 2, 4, 7, 9-11, 19, and 20 are under examination in this office action.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The rejection of claims 1, 2, 4, 6-11, and 19 under 35 U.S.C. 103 as being unpatentable over Mao (of record) in view of CN 116118 (of record) and in view of Topp et al. (of record) has been withdrawn in view of applicant’s claim amendments received March 30, 2026.
Specifically, applicant has amended the claims to recite a composition comprising 3 parts, namely 1) a CD19 positive cell (i.e. a B cell tumor/”target”), 2) the liposome (with antibodies of two different specificities attached thereto), and 3) a CD3 expressing T cell that displays a killer effector phenotype (i.e. the effector cell). The rejection of record pertained only to why it would have been obvious to artisans to make liposomes that simultaneously target CD19 and CD3. There does not appear to be any guidance, direction or motivation in the art (or in the instant specification either, see below) to make a pre-formed complex of target-liposome-effector wherein such a pre-formed complex is then administered to a subject.
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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.
Claims 1, 2, 4, 7, 9-11, 19, and 20 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
Applicant has amended independent claim 1 as part of the March 30, 2026 response to claim a product wherein said product is a preformed complex comprising three parts, 1) a “target” cell which is a B-cell tumor expressing CD19, 2) a liposome comprising anti-CD19 and anti-CD3 antibodies on its surface and 3) an “effector” which a CD3 expressing cytotoxic T cell. The specification discusses administering liposomes decorated with two different antibodies so as to bring effector cells into close proximity with tumor targets via the liposome acting as a “bridge” between the target and cytotoxic effector. For example, administration of a CD19 and CD3 expressing liposome to a B cell cancer patient would serve to recruit pre-existing T cell effectors in the patient to the cancerous B cells which are also already pre-existing in the patient, such that the B cell tumor is killed by the T cell. Note that such a complex only forms in vivo and has a very transient lifetime as the effector kills the target which effectively disassembles such a complex. Thus administration of dual targeted liposomes to treat a cancer patient reasonably is disclosed. However, as discussed above applicant is no longer claiming just the liposome or methods of administering just the liposome as now applicant has claimed products which comprise the B cell target, the liposome, and T effector pre-assembled into a complex and the administration of such complexes to a patient to treat disease (see new claim 20 in particular). The specification as originally filed does not reasonably appear to provide support for the concept of applicant claiming a product comprising the three parts pre-assembled or methods of administering such a preformed complex, and applicant has not pointed out where support for such concepts are located in the specification as originally filed. As such the claim amendments received March 30, 2006 add limitations not reasonably disclosed by applicant at the time of filing (i.e. “new matter”). Removal of the new matter from the claimed invention via amendment or pointing out where clear and unambiguous support for the concepts as presently claimed are disclosed in the specification as originally filed are two possible mays to obviate this rejection.
Claims 1, 2, 4, 7, 9-11, 19, and 20 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.
Applicant has claimed a composition comprising three elements, namely a “target” cell that expresses CD19 (i.e. a B cell tumor), an “effector” cell which is a T cell which expressed CD3 and has cytotoxic activity, and a liposome onto which anti-CD19 and anti-CD3 antibodies are attached so as to form a “bridge” that brings the “target” and “effector” into very close proximity. The specification discloses making liposomes comprising anti-CD19 and anti-CD3 and using such liposomes to target cytotoxic effector T cells to B cell tumors resulting in the destruction of the B cells (see particularly working examples 4 and 5). Thus the specification discloses that liposomes which are decorated with anti-CD19 and anti-CD3 antibodies are to be administered to B cell cancer patients in order to eliminate their B cell population (which includes normal and cancerous B cells as CD19 is essentially universally expressed in mature B cells). Note that in such teachings, both the B cell “target” and the T cell “effector” are pre-existing in the subject/patient, and it is only the dual antibody decorated liposome which is administered to said subject/patient. Note that the idea of administering a reagent, such as a bispecific antibody, that simultaneously binds both the tumor target and the effector cell is extremely widely known in the art, with the instant recited liposomes offering the alleged advantage of being able to alter the ratio between antigen specificities as compared to a bispecific antibody wherein the ratio is always fixed at 1:1. However, as discussed above applicant is no longer claiming just a liposome comprising two different antigen specificities or methods of administering such a liposome to treat cancer but instead is claiming a product which comprises the target cell, the effector cell, and the linking liposome, as well as methods of administering such a tripartite complex to a patient to treat disease.
With regard to the claimed product, if the liposome correctly “works” any T cell brought into close proximity to a B cell target by the liposome will promptly kill the B cell, thus promptly destroying the tripartite complex. As such it does not appear reasonable that a complex comprising the three elements (i.e. target – liposome - effector) exists long enough to be isolated as a product, especially one that needs to be made and then administered to a patient (see claim 20 specifically). Further, no guidance or direction concerning how to isolate and stabilize such tripartite complex appears to be disclosed in the specification as filed. Additionally, claim 1 explicitly recites “wherein the multicellular targeting liposome including the predominant antibody against the target cell and the auxiliary antibody against the effector cell can promote the immune cells to bind and recognize tumor cells, and then activate the effector function of the immune cells” and thus the “target” cells which are part of the claimed complex (and thus necessarily administered as pert claim 20) are tumor cells and the specification fails to identify any reason why artisans would administer additional tumor cells to a patient who is already suffering from cancer. Indeed, administering additional cancer cells to a patient suffering from cancer appears extremely counterintuitive and reasonably is extremely detrimental to the health of the subject/patient based upon the evidence presently of record. In view of all of the above severe questions concerning what artisans would ever bother to make and then use the inventions as presently claimed exist and are not addressed in any reasonable fashion by the disclosure as originally filed.
Therefore, in view of the breadth of the claimed invention, the guidance and direction of the instant specification, and the teachings and knowledge in the art, artisans would be unable to make and use the full breadth of applicant’s inventions as presently claimed without first engaging in additional unpredictable basics science research and experimentation.
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 2, 4, 7, and 19 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.
As per the amendments to claim 1 received 3/30/2026, claim recites a product which is a complex comprising three components, a) a “target” cell expressing CD19, b) an “effector” T cell that expressed CD3 and had cytotoxic activity, and c) a liposome to which anti-CD19 and anti-CD3 antibodies are attached thereto. Dependent claims 2 and 7 recite that the claimed composition (which already necessarily comprises target effector, and liposome as per claim 1) is “capable of simultaneously or sequentially binding to a tumor cell and a lymphocyte”. Such a recitation is illogical. Given that the target and effector are already attached to the liposome in the claimed composition the recitation of “simultaneous or sequential” is not readily interpretable. Artisans reasonably cannot know the order of binding once the three component complex is formed (as per claim 1) and since the components are already present it is unclear what, if anything, applicant is trying to further limit the invention to by reciting “simultaneous or sequential”.
With regard to claim 4, it depends directly from claim 1 which recites that the ratio of predominant to auxiliary antibody on the liposome is in the range of 2:1 to 5:1. This means that minimally there are 2 predominant antibodies for every auxiliary antibody and there are a maximum of 5 predominant antibodies for every auxiliary antibody. Dependent claim 4 recites “wherein each liposome has 1-1000 predominant antibodies and 1-1000 auxiliary antibodies on the surface”. Such a recitation is mathematically impossible. For example, if 1 predominant antibody is present (i.e. the lowest possible number), the auxiliary antibody would need to be 0.5 which is physically nonsensical in addition to not being allowed by the recited claim language. Similarly, if 1000 auxiliary antibodies are present (i.e. the maximum amount allowed per claim 4) minimally there would need to be 2,000 predominant antibodies present which is not allowed per claim 4. As such the claim is indefinite as it allows for conditions which are impossible per the independent claim, and thus it is unclear how artisans are to interpret such impossibilities when making the claimed product.
With regard to claim 19, instead of using standard Markush language (i.e. “wherein the phosphatidyl serine is chosen from the group consisting of ….”) applicant recites “wherein the phosphatidyl choline may be selected from …”. The phrase “may be” is not equivalent in meaning to “must” and thus the list of cholines in in the claim most reasonably is interpreted as exemplification rather than limitation. Specifically, the practitioner “may” choose something from the list but the don’t HAVE to make such a selection and can therefore choose something which isn’t recited at all. Applicant is remined that exemplification in claims is not permissible. See MPEP 2173.05(d).
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 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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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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