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 .
Claim Status
Claims 2, 4-6, 10-34, 36, 41-50, 52, 54-55, 58, 60-66, and 68-70 were canceled.
Claims 1, 3, 7-9, 35, 37-40, 51, 53, 56-57, 59, 67, and 71-72 are pending and under consideration.
Specification
The disclosure is objected to because of the following informalities: Applicant must correct following errors for compliance with 37 CFR 1.835. Instant specification recites “X1KX2 (SEQ ID NO: 51)”, “GKG (SEQ ID NO: 2)” and “GGG (SEQ ID NO: 74)” at pages 32; “SC (SEQ ID NO: 3)” at page 34 for three or fewer amino acid sequence. Sequence identifier must not be assigned to the sequence of three or fewer amino acid residues. Applicant must replace SEQ ID NO: 51, 2, 74 and 3 with actual sequence “X1KX2”, “GKG”, “GGG” and “SC”, respectively, throughout instant specification. Furthermore, Applicant must replace SEQ ID NO: 51-53, 68, 74, 76, 81, 110, 149, 150-153, 155, 158, 160, 162, 167, 169, 171, 174, 179 and 184 with actual sequence throughout instant specification. Applicant is advised to check all SEQ ID NOs to see whether there are more SEQ ID NOs for three or fewer amino acid residues are present in instant specification. If so, Applicant must replace SEQ ID NO for three or fewer amino acid residues with actual sequence throughout instant specification.
Appropriate correction is required. See ST.26 rules.
Claim Objections
Claim 1 is objected to because of the following informalities: “wherein DS1 and/or D2” in line 9 should read “wherein DS1 and/or DS2”. Appropriate correction is required.
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.
Claims 1, 3, 7-9, 35, 37-40, 51, 53, 56-57, 59, 67, and 71-72 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 1 recites that one of B and C comprises SEQ ID NO: 61 as acyl donor because the other of B and C comprises lysine or terminal glycine (SEQ ID NO: 2, 74-75) as acyl acceptor. Instant specification disclosed that acyl donor comprises glutamine and acyl acceptor comprises lysine or N-terminal glycine (paragraph 140 at page 30). However, SEQ ID NO: 61 does not comprises glutamine and instead it comprises lysine (see Table 2 at page 30). Furthermore, Khew et al (Biomaterials 31 (2010) 4600-4608; 5/21/2024 IDS) teaches that EDGFFKI (instant SEQ ID NO: 61) is an amine donor (= acyl acceptor) substrate for tissue transglutaminase and APQQEA (instant SEQ ID NO: 60) is an amine acceptor (=acyl donor) for this enzyme (abstract). Therefore, SEQ ID NO: 61 is acyl acceptor instead of acyl donor. Since instant claim 1 claims SEQ ID NO: 61 as acyl donor, it is unclear whether Applicant intends to recite SEQ ID NO: 61 as acyl donor or acyl acceptor.
Claim 72 recites SEQ ID NO: 18 (SNYSMVNTTNMTSA) which contains alanine at C-terminus. However, Table 13 at page 81-82 of instant specification disclosed glycosylation sequence SNYSMVNTTNMTS which does not contain alanine at C-terminus. Therefore, it is unclear whether glycosylation sequence recited by claim 72 contains alanine at C-terminus or not. Claim 72 will not be further considered for art rejection below because the sequence is unclear.
Claim 1 recites conjunction “or” between wherein-clause in line 5 from bottom, and conjunction “and” in the second line from bottom. Therefore, it is unclear claim 1 require all of wherein-clause (in case of conjunction “and”) or only one of them (in case of conjunction “or”). It is suggested that Applicant amend line 7 to line 2 from bottom to make a single wherein-clause as follows.
FROM:
wherein B comprises a sequence selected from the group consisting of: SEQ ID NOs: 1, 53-62, 124, 127, 128, 129, 130, 131, and 132-139 and C comprises a sequence selected from the group consisting of: SEQ ID NOs: 2 and 74-75, or wherein B comprises a sequence selected from the group consisting of: SEQ ID NOs: 2 and 74-75 and C comprises a sequence selected from the group consisting of: SEQ IDNOs: 1, 53-62, 124, 127, 128, 129, 130, 131, and 132- 139
TO:
wherein (i) B comprises a sequence selected from the group consisting of: SEQ ID NOs: 1, 53-62, 124, 127, 128, 129, 130, 131, and 132-139 and C comprises a sequence selected from the group consisting of: SEQ ID NOs: 2 and 74-75; or (ii) B comprises a sequence selected from the group consisting of: SEQ ID NOs: 2 and 74-75 and C comprises a sequence selected from the group consisting of: SEQ IDNOs: 1, 53-62, 124, 127, 128, 129, 130, 131, and 132-139
All claims which depend from claim 1 also contain same claim limitation and therefore they are rejected as well.
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 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, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2016/0185875 (hereinafter US875; 5/21/2024 IDS), Yusuke Tanaka et al (Org. Biomol. Chem., 2007, 5, 1764-1770; 5/21/2024 IDS), and Tsutomu Tanaka et al (FEBS Letters 579 (2005) 2092-2096; 5/21/2024 IDS).
Regarding claim 1 and 3, US875 teaches antibody-based therapeutic agent which is capable of being selectively activated in a target cell or tissue to treat a condition in the target cell or tissue (paragraph 010). US875 teaches that the hinge antibody comprises a functional antibody, two inhibitory domains, and four cleavable linkers (paragraph 011, see below for Figure 1). The functional antibody is capable of treating the condition in an activated state and comprises two light chains and two heavy chains. Each of the two inhibitory domains consists of two peptide arms (corresponding to S1 and S2 of instant application) interconnected by disulfide bonds. Each of the four cleavable linkers (corresponding to DS1 and DS2 of instant application) comprises a peptide substrate cleavable by an enzyme that is specifically or highly expressed in the target cell or tissue. Each cleavable linker connects one of the two peptide arms of the two inhibitory domains to the N-terminals of one of the two light chains and two heavy chains of the functional antibody (paragraph 011). The cysteine residues for the disulfide bonds in the inhibitory domain of US875 correspond to association moieties B and C.
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US875 teaches that each of the inhibitory domain comprises the amino acid sequence of SEQ ID NO: 10 (paragraph 015). SEQ ID NO: 10 comprises 15 amino acid residues (page 19).
US875 teaches that the peptide substrate is cleavable by any of the following enzyme: a matrix metalloproteinase (e.g., MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and MMP-14), a cathepsin (e.g., CTS A, CTS B, CTS D, CTS E and CTS K) [0070].
Regarding claim limitation “association of S1 with S2 spans a length greater than about 35 A”, since each of the inhibitory domain comprises the amino acid sequence of SEQ ID NO: 10 which is 15 amino acid long, the association of S1 with S2 comprises 30 amino acid residues. Since extended conformation in a beta strand is about 3.5 A per residue, the association of S1 with S2 spans a length of about 105 A.
Regarding claims 37-38, US875 teaches that each cleavable linker comprises same sequence (claim 9).
Regarding claim 39, the function of disease-sensing releasable moiety (DS1 and DS2) is release of shield moiety at the location of target cell (e.g. tumor microenvironment). Therefore, one of ordinary skill in the art would understand that any protease expressed in tumor microenvironment will cleave the shield moiety. There are finite number of proteases which are expressed at the tumor microenvironment and therefore there are finite number of identified predictable solutions. Choosing a protease from these options are arbitrary. Furthermore, there are two possible options for two DS1 and DS2 (i.e. same or different). It would have been obvious to one of ordinary skill in the art to try the finite number of identified predictable solutions through routine experimentation.
Regarding claim 51 and 53, US875 teaches that the inhibitory domain proposed in this disclosure can be attached to the N-termini of a bispecific antibody (e.g., catumaxomab) in a way similar to those discussed herein (paragraph 155). Other antibody-based therapeutics suitable for use in the present invention include, but are not limited to, bispecific diabody, trispecific Fab3 antibodies, bivalent minibodies, triabody, tetrabody, scFv fragments, Fab fragments, and Bis-scFv fragments (paragraph 155).
Regarding claim 57, US875 teaches that the functional antibody is … anti-CTLA-4 antibody, anti-HER2 antibody, anti-EGFR antibody, … , anti-CD3 antibody (paragraph 013).
Regarding claim 59, US875 teaches that the hinge structures of the inhibitory domains 120, upon being attached to the functional antibody 110, sterically mask the ligand-binding site of the functional antibody 110 (paragraph 064). Therefore, the cleaving of the cleavable linkers will unblock the binding of the antibody to its target.
Regarding claim 67, US875 teaches that in addition to the hinge antibody, said pharmaceutical composition further comprises a pharmaceutically-acceptable carrier (paragraph 093).
However, US875 does not teach that B and C are conjugated to each other by an isopeptide bond which is catalyzed by transglutaminase.
Regarding claim 1 and 7, Yusuke Tanaka teaches cross linking between LLQG tag (instant SEQ ID NO: 1) and lysine residue catalyzed by microbial transglutaminase (abstract). Yusuke Tanaka teaches that transglutaminase catalyzes acyl transfer reaction between glutamine residue and a variety of primary amines (acyl acceptors), including the amino-group of lysine (page 1764, right column, last paragraph).
Tsutomu Tanaka teaches that microbial transglutaminase can catalyze transglutamination reaction between glutamine and N-terminal amino group of glycine of GGG-EGFR (Figure 1 and Figure 3A). Therefore, Tsutomu Tanaka teaches instant SEQ ID NO: 74 (GGG) as acyl acceptor.
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have replaced disulfide bond of US875 with isopeptide bond taught by Yusuke Tanaka and Tsutomu Tanaka in order to make alternative activatable antibody because isopeptide bond system is chemical cross-linking well known in the art as disulfide bond is a well-known chemical cross-linking. One of ordinary skill in the art would be able to recognize that disulfide bond and isopeptide bond are alternative chemical cross linking which are well known in the art. Because disulfide bond can be disrupted in reduction environment, one of ordinary skill in the art would be motivated to replace disulfide bond with isopeptide which is not disrupted by change of oxidation potential and test alternative activatable antibody to find a better therapeutic agent.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because isopeptide bond can be formed by transglutaminase as taught by Yusuke Tanaka.
However, US875 does not teach GKG (SEQ ID NO: 2) as acyl acceptor.
Regarding claim 8, as discussed above, Yusuke Tanaka and Tsutomu Tanaka teaches LLQG (SEQ ID NO: 1) as acyl donor and GGG as acyl acceptor. Since Yusuke Tanaka teaches that transglutaminase catalyzes acyl transfer reaction between glutamine residue and a variety of primary amines (acyl acceptors) including the amino-group of lysine (page 1764, right column, last paragraph), it would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have replaced glycine in GGG with lysine to make alternative acyl acceptor sequence. There would be finite number of possible solutions (i.e. GGK, GKG, KGG).
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have tried the finite number of identified predictable solutions through routine experimentation. Therefore, LLQG (SEQ ID NO: 1) as acyl donor and GKG (SEQ ID NO: 2) as acyl acceptor would be obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because it was well known in the art that any sequence including lysine would work as acyl acceptor because Yusuke Tanaka teaches that transglutaminase catalyzes acyl transfer reaction between glutamine residue and a variety of primary amines (acyl acceptors) including the amino-group of lysine.
However, US875 does not teach that S1 comprises DS1 and S2 does not comprise DS2; or S2 comprises DS2 and S1 does not comprise DS1.
Regarding claim 35, there are finite number of possible solutions for DS1 and DS2: (a) both of S1 and S2 comprise DS1 and DS2, respectively; (b) S1 comprises DS1 and S2 does not comprise DS2; and (c) S2 comprises DS2 and S1 does not comprise DS1.
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have tried the finite number of identified predictable solutions through routine experimentation. One of ordinary skill in the art would be able to predict that if at least one of two disease sensing releasable moiety (DS1 and DS2) is cleaved off, the shield moieties S1 and S2 cannot block binding of the ABD to its target because both linkers are required to hold shield moieties S1 and S2 fixed in three-dimensional space. Therefore, both S1 and S2 do not need to comprise disease sensing releasable moiety (DS1 and DS2). Therefore, the invention as a whole would be obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because finding alternative activatable antibody with different configuration of DS1 and DS2 through routine experimentation is obvious to one of ordinary skill in the art. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 3, 7-8, 35, 37-40, 51, 53, 57, 59 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2016/0185875, Yusuke Tanaka et al, and Tsutomu Tanaka et al as applied to claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67 above, and further in view of DeCoux et al (Journal of Molecular and Cellular Cardiology 77 (2014) 64-72; 5/21/2024 IDS).
Regarding Claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67, teachings of US875, Yusuke Tanaka and Tsutomu Tanaka were discussed above.
However, US875 and Yusuke Tanaka and Tsutomu Tanaka do not teach that DS1 and/or DS2 comprises SEQ ID NO: 171.
Regarding claim 40, DeCoux teaches that the consensus sequence for the MMP-2 cleavage site is XPXX(L/I)XXX (where X is any amino acid) which is same sequence as instant SEQ ID NO: 171 (page 65, right column, second paragraph; see also instant specification, page 46, paragraph 188).
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used specific MMP-2 cleavage site (instant SEQ ID NO: 171) taught by DeCoux because DeCoux teaches that specific MMP-2 cleavage site (instant SEQ ID NO: 171) can be effectively cleaved by MMP-2 protease. One of ordinary skill in the art would understand that any protease expressed by cancer cell can be used to cleave off the shield moieties and it is well known in the art that MMP-2 protease is one of most studied proteases expressed in cancer microenvironment. Therefore, the invention as a whole would be obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because specific MMP-2 cleavage site (instant SEQ ID NO: 171) can be effectively cleaved off by MMP-2 protease expressed in cancer microenvironment. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 3, 7-8, 35, 37-39, 51, 53, 56-57, 59 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2016/0185875, Yusuke Tanaka et al, and Tsutomu Tanaka et al as applied to claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67 above, and further in view of US2019/0016819 (hereinafter US819; 5/21/2024 IDS).
Regarding Claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67, teachings of US875, Yusuke Tanaka and Tsutomu Tanaka were discussed above.
However, US875 and Yusuke Tanaka and Tsutomu Tanaka do not teach that the antibody is an antibody-drug conjugate.
Regarding claim 56, US819 teaches that in general, the probody comprises at least an antibody or antibody fragment thereof (collectively referred to as “AB”), capable of specifically binding a target, wherein the AB is modified by a masking moiety (MM) (paragraph 150). US819 teaches “When the AB is modified with a MM and is in the presence of the target, specific binding of the AB to its target is reduced or inhibited, as compared to the specific binding of the AB not modified with an MM or the specific binding of the parental AB to the target” (paragraph 150). Masking moiety corresponds to shield moiety of instant claims. US819 teaches an activatable antibody (paragraph 151). US819 teaches antibody-drug conjugate (paragraph 007).
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have replaced antibody portion of US875, Yusuke Tanaka and Tsutomu Tanaka with antibody-drug conjugate of US819 in order to make alternative activatable antibody-drug conjugate. One of ordinary skill in the art would be able to envision that shield moiety can also be attached to the antibody portion of antibody-drug conjugate. Because antibody-drug conjugate comprises drug moiety which is toxic to cells, one of ordinary skill in the art would be motivated to attach shield moiety to antibody-drug conjugate to make activatable antibody-drug conjugate which can be activated only in the cancer microenvironment in order to reduce side effect. Therefore, the invention as a whole would be obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because one of ordinary skill in the art would be able to envision that shield moiety can also be attached to the antibody portion of antibody-drug conjugate because prior art teaches antibodies with shield moieties. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59, 67 and 71 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2016/0185875, Yusuke Tanaka et al, and Tsutomu Tanaka et al as applied to claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67 above, and further in view of US2010/0178292 (hereinafter US292; 5/21/2024 IDS).
Regarding Claims 1, 3, 7-8, 35, 37-39, 51, 53, 57, 59 and 67, teachings of US875, Yusuke Tanaka and Tsutomu Tanaka were discussed above.
However, US875 and Yusuke Tanaka and Tsutomu Tanaka do not teach that S1 and/or S2 further comprises glycosylation peptide sequence.
Regarding claim 71, US292 teaches that lectin-glycan complex formation [0074].
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have designed masking moiety to further comprise lectin-glycan complex because lectin-glycan complex is dimerizing element well known in the art. One of ordinary skill in the art would envision that any dimerizing element can be used as shield moiety because US875 teaches that two peptides comprising cysteine can form disulfide bond and can be used as shield moieties. Because US292 teaches that lectin-glycan complex formation, one of ordinary skill in the art would be motivated to fuse lectin (glycan-binding protein) to one of heavy chain and light chain of antibody and fuse glycosylation peptide sequence (glycan attachment signal) to the other chain to make dimerization element to form shield moiety. When each chain of antibody is expressed inside cell, glycan will be attached to glycosylation sequence and then lectin of the other chain of antibody will bind to the glycan to form shield moiety. One of ordinary skill in the art would be motivated to test this lectin-glycan dimerization element as shield moiety to see whether this lectin-glycan system can function better as a shield moiety. One of ordinary skill in the art would envision that lectin-glycan complex might be a better shield moiety by blocking antigen binding more efficiently due to its bulkier size than disulfide bond of US875. Therefore, the invention as a whole would be obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because lectin-glycan complex is dimerizing element well known in the art and because one of ordinary skill in the art would envision that lectin-glycan complex might be a better shield moiety by blocking antigen binding more efficiently due to its bulkier size than disulfide bond of US875. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 7-9, 37-38, 40, 51, 53, 56-57, 67, and 71-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,939,385 (hereinafter patent’385; 7/25/2024 IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 1, 3 and 8-9, claim 1 of patent’385 claims
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SEQ ID NO: 140 comprises LLQG (SEQ ID NO: 1) and SEQ ID NO: 141 comprises GKG (SEQ ID NO: 2).
Regarding claim 7, claim 2 of patent’385 claims “The activatable antibody of claim 1, wherein B and C are conjugated to each other by a transglutaminase”.
Regarding claim 37-38 and 40, SEQ ID NO: 140 and 141 comprises LSGRSDNH (SEQ ID NO: 19) which is protease substrate.
Regarding claim 51, claim 3 of patent’385 claims “The activatable antibody of claim 1, wherein the antibody is a bispecific antibody”.
Regarding claim 53, claim 4 of patent’385 claims “The activatable antibody of claim 1, wherein the antibody is a Fab, a (Fab)2, an Fv, or a full-length antibody”.
Regarding claim 56, claim 5 of patent’385 claims “The activatable antibody of claim 1, wherein the antibody is an antibody-drug conjugate (ADC)”.
Regarding claim 57, claim 6 of patent’385 claims “The activatable antibody of claim 1, wherein the ABD specifically binds to EGFR, CTLA-4, PD-1, CD-71, PD-L1, HER2, CD3, a-4 integrin, a-V integrin, a-4-b-1 integrin, a-4-b-7 integrin, AGR2, Anti-Lewis_Y, Apelin J receptor, APRIL, B7-H3, B7-H4, BCMA, BTLA, C5 complement, C-242, CA9, CA19-9, Carbonic anhydrase 9, CD2, CD3, CD6, CD9, CD11a, CD19, CD20, IL27, IL27R, IL29, IL31, IL31R, Insulin Receptor, Jagged-1, Jagged-2, KIR, LAG-3, LIF-R, Lewis X, LIGHT, LRP4, LRRC26, CD22, CD24, CD25, CD27, CD28, CD30, CD40, CD40L, CD41, CD44, CD44v6, CD47, CD51, CD52, CD56, CD64, CD70, CD71, CD74, CD80, CD81, CD86, CD95, CD117, MCSP, Mesothelin, MRP4, MUC1, Mucin-16, Na/K ATPase, Neutrophil elastase, NGF, Nicastrin, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NOV, OSM-R, CD125, CD132, CD133, CD137, CD138, CD166, CD172A, CD248, CDH6, CEACM5, CEACAM6, CLAUDIN-3, CLAUDIN-4, cMet, Collagen, Cripto, CSFR, CSFR-1, CTLA-4, CTFG, CXCL10, CXCL13, CXCR1, CXCR2, OX-40L, OX-40R, PAR2, PDGF-AA, PDGF-BB, PDGFRa, PDGFRb, PD-1, PD-L1, PD-L2, Phospahtidyl-serine, P1GF, PSCA, PSMA, RAAG12, CXCR4, CYR61, DL44, DLK1, DLL4, DPP-4, DSG1, EGFR, EGFRVIII, Endothelin b receptor (ETBR), ENPP3, EPCAM, EPHA2, EPHB2, ERBB3, F protein of RSV, FAP, FGF-2, FGF-8, FGFR-1, FGFR-2, FGFR-3, FGFR-4, Folate receptor, RAGE, SLC44A4, TNFa, STEAP1, STEAP2, TAG-72, TAPA1, TGFb, TIGIT, TIM3, TLR2, TLR4, TLR6, TLR7, TLR8, GAL3STI, G-CSF, G-CSFR, GD2, GITR, GLUT1, GLUT4, GM-CSF, GM-CSFR, GPIIb/IIIa receptor, Gp130, GPNIVIB, GRP78, HER-2/neu, HGF, hGH, HVEM, Hyaluronidase, ICOS, INFa, INFb, INFg, IgE, TLR9, TMEM31, Sphingosine 1, Phosphate, TNFR, TNFRS12A, TRAIL-R1, TRAIL-R2, Transferrin, Transferrin Receptor, TRK-A, TRK B, uPAR, VCAM-1, VEGF, VEGF-A, IgE Receptor, IGF, IGF1R, IL1B, IL1R, IL2, IL2R, IL4, IL4R, IL6, IL6R, IL11, IL12, IL12p40, IL12R, IL12Rbl, IL13, IL13R, IL15, IL17, IL18, IL21, IL23, IL23R, VEGF-B, VEGF-C, VEGF-D, VEGFR1, VEGFR2, VEGFR3, VISTA, WISP-1, WISP-2, or WISP-3”.
Regarding claim 67, claim 7 of patent’385 claims “A pharmaceutical composition comprising the activatable antibody of claim 1 and a pharmaceutically acceptable carrier.”
Regarding claim 71, claim 8 of patent’385 claims “The activatable antibody of claim 1, wherein S1 and/or S2 further comprises a glycosylation peptide sequence.”
Regarding claim 72, claim 9 of patent’385 claims “The activatable antibody of claim 8, wherein the glycosylation peptide sequence comprises the amino acid sequence of SEQ ID NO: 18.”
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached at 571-272-0835. 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.
/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/GARY B NICKOL/Supervisory Patent Examiner, Art Unit 1645