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 .
Applicant’s response and amendments received August 24, 2026 are acknowledged.
Claims 2,3, 5-8, and 12-18 have been canceled.
Claims 1, 4, 9-11, 19 and 20 have been amended.
Claims 1, 4, 9-11, 19, and 20 are pending in the instant application.
Claims 1, 4, 9-11, 19, and 20 are under examination in this office action.
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.
The rejection of claims 1, 2, 4, 7, 9-11, 19, and 20 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), first paragraph, as failing to comply with the written description requirement because of new matter has been withdrawn in view of applicant’s claim amendments received as part of the August 24, 2026 response.
The rejection of claims 1, 2, 4, 7, 9-11, 19, and 20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement has been withdrawn in view of applicant’s claim amendments received August 24, 2026.
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.
The rejection of claims 2, 4, 7, and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of applicant’s claim amendments received August 24, 2026 which adequately address the issues discussed in the prior 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.
Claims 1, 4, 9-11, 19, and 20 are rejected 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).
Mao discloses dual ligand immunoliposomes (immunoliposomes which display two antibodies on their surface) wherein the pairs of antibodies on such constructs include anti-CD37 in combination with either anti-CD19 or anti-CD20 (see entire document, particularly Chapter 2). Notably, such constructs are disclosed as being useful for treating leukemia and killing cells via antibody crosslinking alone as no anti-cancer payloads were delivered (i.e. a “blank” liposome, see for example section 2.3.7, Figure 2.8, and page 65). Note that ratios of the two antibodies different from 1:1 were made and tested (see in particular section 2.3.4 and Figure 2.5). Such immunoliposomes contain phosphatidylcholine and cholesterol, and were made by conjugation of the antibodies to maleimide groups in the lipids (see particularly sections 2.2.1 and 2.2.7 as well as Chapter 1 and Figure 1.5). Antibodies used in targeting immunoliposomes are disclosed as being full length antibodies as well as antigen binding fragments thereof including Fab’ and scFv (see for example pages 13 and 18-21). Indeed, Mao explicitly teaches on page 21 that “To overcome immunogenicity and also to maximize the binding efficiency, F(ab’)2, Fab’, and scFv fragments lacking the Fc domain but with complementary activating regions are useful for ILP immobilization” (note that “ILP” stands for immunoliposome, see for example page 18 pf Mao et al). Various liposome formulation components, including egg phosphatidylcholine, are disclosed (see for example section 1.2.1.1 as well as Figure 1.2 and Table 1.1). Such inventions differ from that which is presently claimed in that the “auxiliary” antibodies binding lymphocytes in the compositions of Mao bind to B cells rather than to T cells expressing CD3 as is presently claimed.
The ‘118 document discloses making and using bispecific liposomes that surface express an anti-tumor antibody and an anti-T cell antibody to treat cancer (see entire translation, particularly page 3, the sentence spanning pages 3 and 4, and the paragraph immediately preceding the Example on page 5). Notably the anti-T cell antibody is disclosed as being the well-known anti-CD3 antibody named OKT3 (see the top of page 6). The ratio between the two antibodies can vary, with the working example disclosing a 5:1 ratio between the anti-tumor antibody and the anti-CD3 antibody (see particularly the working example).
Topp et al. disclose that the bispecific T cell engager blinatumomab which binds CD3 and CD19 and brings CD3 expressing T cells into contact with CD19 expressing tumor cells is effective in treating acute lymphoblastic leukemia (ALL) in human patients (see entire document, particularly the abstract).
Therefore, it would have been obvious to a person of ordinary skill to modify the antibody targeted liposomes of Mao to target other antigen specificities such as CD3 in order to redirect killing to tumor types distinct from those taught by Mao. Artisans would have been motivated to do so since immunoliposomes targeting CD3 and tumor antigens were known for treating leukemia in the art as evidenced by the ‘118 document, with the combination of anti-CD3 and anti-CD19 being highly desirable in treating leukemia as taught by Topp et al. In particular, artisans would know that targeting CD19 and CD3 in the same compound successfully targets CD3 expressing T cells to CD19 expressing B cell tumors in human leukemia as taught by Topp et al. and that such killing activity occurs in the absence of additional drugs being conjugated to the bispecific T cel engager. Given that dual ligand immunoliposomes not loaded with chemotherapeutics can be successfully used to treat cancers including leukemia as taught by Mao, it would be obvious that other antibody pairs known to treat cancers including leukemia could be combined in immunoliposomes and used for the same purpose, with the advantage of dual ligand immunoliposomes over traditional bispecific reagents being that the ratio between the two antibodies can readily varied and optimized in an immunoliposome as readily demonstrated by Mao and the ‘118 document whereas the bispecific T cell engagers of Topp et al. are fixed at a 1 to 1 ratio which cannot be optimized for therapeutic purposes. Given the use of liposomes comprising two antibodies to different antigens as shown by both Mao and the ‘118 document, and the ability of dual specificity regents to kill targets in the absence of additional chemotherapeutic agents as shown by Mao and Topp et al., artisans would have a reasonable expectation of success when making blank liposomes that display two different antibodies on their surface at ratios greater than 1 to 1. Note further that artisans would also be motivated to use antigen binding fragments of antibodies, such as scFv, rather than whole antibody in order to gain the advantage of reduced immunogenicity as taught by Mao.
Claims 1, 4, 9-11, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Leszczniecka et al. (WO 2017/123627) in view of CN 116118 (of record) in view of Topp et al. (of record) and in view of Mao (of record).
Leszczniecka et al. disclose compositions comprising empty liposomes decorated with antibodies specific for two different antigens to simultaneously target an immune effector cell and a tumor cell (see entire document, particularly the abstract, claims, paragraphs [0029-0037], and Figure 1). Such antibodies are disclosed as disclosed as being joined to the liposome via maleimide linkers and thiol chemistry (see particularly working example 11) and as offering the advantage as being able to vary the ratio between the antigen specificities unlike bispecific antibodies where the ratio is fixed at 1:1, with many ratios including 10:1, 5;1, and 3:2, (see for example paragraphs [0027], [0032], and examples 11-12). Notably, the ability of such reagents to target T cells to tumor cells is explicitly disclosed, as is the administration of such constructs to treat cancer (see for example paragraphs [0037-0038] and well as examples 8-10). Such teachings differ from what is presently claimed in that the bispecific liposomes of Leszczniecka et al. are not disclosed as binding CD19 and CD3, nor are the antibodies disclosed as necessarily being fragments such as Fab’, Fab, F(ab’)2 or scFv.
The ‘118 document discloses making and using bispecific liposomes that surface express an anti-tumor antibody and an anti-T cell antibody to treat cancer (see entire translation, particularly page 3, the sentence spanning pages 3 and 4, and the paragraph immediately preceding the Example on page 5). Notably the anti-T cell antibody is disclosed as being the well-known anti-CD3 antibody named OKT3 (see the top of page 6). The ratio between the two antibodies can vary, with the working example disclosing a 5:1 ratio between the anti-tumor antibody and the anti-CD3 antibody (see particularly the working example).
Topp et al. disclose that the bispecific T cell engager blinatumomab which binds CD3 and CD19 and brings CD3 expressing T cells into contact with CD19 expressing tumor cells is effective in treating acute lymphoblastic leukemia (ALL) in human patients (see entire document, particularly the abstract).
Mao discloses dual ligand immunoliposomes (immunoliposomes which display two antibodies on their surface) wherein the pairs of antibodies on such constructs include anti-CD37 in combination with either anti-CD19 or anti-CD20 (see entire document, particularly Chapter 2). Notably, such constructs are disclosed as being useful for treating leukemia and killing cells via antibody crosslinking alone as no anti-cancer payloads were delivered (i.e. a “blank” liposome, see for example section 2.3.7, Figure 2.8, and page 65). Note that ratios of the two antibodies different from 1:1 were made and tested (see in particular section 2.3.4 and Figure 2.5). Such immunoliposomes contain phosphatidylcholine and cholesterol, and were made by conjugation of the antibodies to maleimide groups in the lipids (see particularly sections 2.2.1 and 2.2.7 as well as Chapter 1 and Figure 1.5). Antibodies used in targeting immunoliposomes are disclosed as being full length antibodies as well as antigen binding fragments thereof including Fab’ and scFv (see for example pages 13 and 18-21). Indeed, Mao explicitly teaches on page 21 that “To overcome immunogenicity and also to maximize the binding efficiency, F(ab’)2, Fab’, and scFv fragments lacking the Fc domain but with complementary activating regions are useful for ILP immobilization” (note that “ILP” stands for immunoliposome, see for example page 18 pf Mao et al). Various liposome formulation components, including egg phosphatidylcholine, are disclosed (see for example section 1.2.1.1 as well as Figure 1.2 and Table 1.1).
Therefore, it would have been obvious to a person of ordinary skill to modify the antibody targeted liposomes of Leszczniecka et al. to target other antigen specificities such as CD3 and CD19 to treat cancers as disclosed by Leszczniecka et al. Artisans would have been motivated to do so since immunoliposomes targeting CD3 and tumor antigens were known for treating leukemia in the art as evidenced by the ‘118 document, with the combination of anti-CD3 and anti-CD19 being highly desirable in treating leukemia as taught by Topp et al. In particular, artisans would know that targeting CD19 and CD3 in the same compound successfully targets CD3 expressing T cells to CD19 expressing B cell tumors in human leukemia as taught by Topp et al. and that such killing activity occurs in the absence of additional drugs being conjugated to the bispecific T cel engager. Given that dual ligand immunoliposomes not loaded with chemotherapeutics can be successfully used to treat cancers as taught by Leszczniecka, it would be obvious that other antibody pairs known to treat cancers including leukemia could be combined in immunoliposomes and used for the same purpose, with the advantage of dual ligand immunoliposomes over traditional bispecific reagents being that the ratio between the two antibodies can readily varied and optimized in an immunoliposome as was explicitly taught by Leszczniecka et al. Note further that artisans would also be motivated to use antigen binding fragments of antibodies, such as scFv, rather than whole antibody in order to gain the advantage of reduced immunogenicity as taught by Mao when making antibody decorated liposomes.
No claims are allowable.
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.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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