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 .
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-4, 6-7, 9, 12-14, 16-19, 22, 24, 26, 28 and 118-121 in the reply filed on December 17, 2025 is acknowledged. New claims 118-121 have been added. Claims 1-4, 6-7, 9, 12-14, 16-19, 22, 24, 26, 28 and 118-121 are pending and under examination in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 17, 2025, October 7, 2025 and April 15, 2025 have been considered by the examiner.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-4, 6-7, 9, 12, 14, 16-19, 22, 24, 26, 28 and 118-121 are rejected under 35 U.S.C. 103 as being unpatentable over Wiklander (WO 2018/015535 in IDS on 4/15/2025) in view of Xu et al. (US 2018/0327494).
Regarding claims 1-4, 7, 9, 12, 14-19, 22, 24 and 119-121. Wiklander teaches a composition comprising an extracellular vesicle, comprising an adapter polypeptide comprising a peptide sequence that binds to an Fe region of an antibody, wherein said adapter polypeptide comprises an extracellular domain and c. at least one therapeutic within the cellular vesicle (see claims 1-23, Examples 1-4, page 18, page, 21, and 36).
Regarding claims 3-4. Wiklander teaches tumor homing peptide, a tumor targeting domain, and the Fc receptor comprising FcyRI (CD64) (see Examples 1-4, page 18, page, 21, and 36).
Regarding claim 6. Wiklander teaches a covalent and non-covalent fusion/attachment of the targeting domain to the extracellular domain (see pages 5-6, page 18).
Regarding claim 12. Wiklander teaches a humanized IgG antibody (see page 19).
Regarding claims 26 and 28. Wiklander teaches a method of treating a subject (see page 9, third paragraph; page 43, second paragraph), said method comprising administering a therapeutically effective amount of a pharmaceutical composition to said subject (said method comprising administering a pharmaceutical composition to said subject; abstract; page 9, third paragraph; page 43, second paragraph), wherein said pharmaceutical composition comprises said composition (wherein said pharmaceutical composition comprises said composition; abstract); a method of producing a composition, said method comprising: a. transfecting an extracellular vesicle donor cell with at least one heterologous polynucleotide encoding an adapter polypeptide (method of producing a composition, said method comprising: a. transfecting an extracellular vesicle donor cell with at least one heterologous polynucleotide encoding an adapter polypeptide; page 37, first paragraph; page 49, second paragraph; page 36, first paragraph; claims 17, 19), wherein said adapter polypeptide comprises a peptide sequence that is at least 70% identical to a Fc receptor, wherein said Fc receptor recognizes a Fc region of an antibody (wherein said adapter polypeptide comprises a peptide sequence that is at least 70% identical to a Fc receptor, wherein said Fc receptor recognizes a Fc region of an antibody; (see page 36, first paragraph); b. collecting an extracellular vesicle released from said extracellular vesicle donor cell (collecting an extracellular vesicle released from said extracellular vesicle donor cell; page 36, first paragraph), wherein said extracellular vesicle released from said extracellular vesicle donor cell expresses said adapter polypeptide, wherein said adapter polypeptide comprises an extracellular domain (wherein said extracellular vesicle released from said extracellular vesicle donor cell expresses said adapter polypeptide, wherein said adapter polypeptide comprises an extracellular domain; (see page 36, first paragraph).
Wiklander does not disclose wherein said adapter polypeptide comprises an extracellular domain; b. said antibody complexed with said adapter polypeptide, wherein said antibody binds a first cell-surface marker and c. complexing said antibody to said extracellular domain, wherein said antibody binds a first cell-surface marker.
Xu teaches an adapter polypeptide comprising a peptide sequence that binds to an Fc region of an antibody (PDL1-Fc fusion protein wherein the Fc region (adapter polypeptide) is from the human IgG1-Fc (comprising a peptide sequence that binds to an Fc region); wherein said antibody complexed with said adapter polypeptide, wherein said antibody binds a first cell-surface marker associated with a diseased cell (see paragraphs [0092], [(0216]-(0217]), wherein said adapter polypeptide comprises an extracellular domain (antibodies specifically bind to PDL1 without binding to Fc (wherein said adapter polypeptide comprises an extracellular); paragraphs [0198]-[0199]); b. said antibody complexed with said adapter polypeptide (PDL1 binding molecule complexed with Fc region (said antibody complexed with said adapter polypeptide); paragraphs [0006], [0072], [0092), [0216]), wherein said antibody binds a first cell-surface marker (said antibody binds a first cell-surface marker; paragraphs [0006], [0072], [0092], [0216]); administering a therapeutically effective amount (administering a therapeutically effective amount; claim 21); polynucleotide encoding an adapter polypeptide (polynucleotide encoding an adapter polypeptide; paragraph [0216]), wherein said adapter polypeptide comprises a peptide sequence that is at least 70% identical to a Fc receptor (wherein said adapter polypeptide comprises a peptide sequence that is at least 70% identical to a Fe receptor; (see paragraph [0216]).
Regarding present claim 9. Xu teaches cell surface marker PD-L1 (see paragraphs [0079], [00177], Example 1).
Regarding claims 17 and 18. Based on the teachings in Xu it would have been within the skill of the ordinary artisan to optimize the conditions of an antibody configuration to complex with the adapter polypeptide in an acidic environment.
Regarding present claim 118. Xu teaches dissociation constant (see paragraph [0073] Typically, the PDL1-binding molecules of the invention will bind to the antigen (i.e., PDL1) with a dissociation constant (KD) of 10.sup.−7 to 10.sup.−11 moles/liter (M), and preferably 10.sup.−8 to 10.sup.−11 moles/liter, more preferably 10.sup.−9 to 10.sup.−11 moles/liter, and even more preferably 10.sup.−10 to 10.sup.−11 moles/liter or less (as measured in a Biacore or in a KinExA assay), and/or with an association constant (KA) of at least 10.sup.7 M.sup.−1, preferably at least 10.sup.8 M.sup.−1, more preferably at least 10.sup.9 M.sup.−1, more preferably at least 10.sup.10 M.sup.−1, such as at least 10.sup.10 M.sup.−1. Any KD value greater than 10.sup.−4 M is generally considered to indicate non-specific binding).
Based on the teachings in Xu it would have been within the skill of the ordinary artisan to optimize the dissociation constant Kd to less of equal 10-9 M.
It is noted that the intended use of the extracellular vesicle recited in the present claim 120 is not limiting to the structure of the claimed extracellular vesicle.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of Wiklander to include, the adapter of Xu, because Xu teaches that programmed death ligand 1 (PDL1) binding molecule is especially useful for treating and/or preventing or diagnosing PDL1 relating diseases such as tumor.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Wiklander (WO 2018/015535 in IDS on 4/15/2025) in view of Xu et al. (US 2018/0327494) as applied to claim 1 and further in view of Jung et al. (US Patent Application Publication US 2018/0208657).
Wiklander and Xu teach the claimed invention as discussed above. They do not teach anti-EGFR antibody clone C225.
Jung teaches A recombinant antibody molecule consisting of a Fab fragment comprising a first binding site for a first antigen, a variable domain of either the light chain or the heavy chain of a second binding site for a second antigen and an immunoglobulin CH2 domain, wherein the Fab fragment and the variable domain are linked via the CH2 domain, wherein in the immunoglobulin CH2 domain at least one cysteine residue that is able to form a disulfide bridge for dimerisation is lacking or mutated (see claims 1-15).
Jung teaches anti-EGFR antibody clone C225 (see paragraph [0222] Immunoglobulin V regions were combined with the desired constant C regions in an expression vector. The cloning procedure indicated here allows the introduction of complete Ig V regions and their expression in lymphoid cells without any alterations of their amino acid sequence. To this end, the nucleotide sequence of a VDJ and VJ fragment of a monospecific antibody was used to design primer pairs (C C′; D D′; Table 1). The reamplified DNA fragments of the V segments were digested (VJ directly and VDJ after reamplification with primer pair E E′ Table 1) with appropriate restriction nucleases (summarized in Table 1) and then ligated into the expression vectors. Alternatively, the V domains were synthezised as DNA fragments at GeneArt, Regensburg, or at Eurofins, Ebersberg, Germany. This method was used for genes coding for the V regions of the antibody directed to EGFR (clone C225). The vectors (FIG. 7) contain human heavy and human light constant region genes. Thus, insertion of the amplified and digested V segments reconstitutes the original genomic organisation of the Ig genes in the vectors without altering any amino acid of the V regions.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of Wiklander to include, the adapter of Xu, and to use the anti-EGFR antibody clone C225 of Jung because Jung teaches that the C225 antibody allows the introduction of complete Ig V regions and their expression in lymphoid cells without any alterations of their amino acid sequence. To this end, the nucleotide sequence of a VDJ and VJ fragment of a monospecific antibody was used to design primer pairs.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648
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