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 .
Claims 1-42 and 61-64 are canceled. Claims 47, 51, 55, 59, 60 have been amended. Claims 65 and 66 have been added. Claims 43-60, 65 and 66 are pending and examined on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Claim 48, 52, 53, 56, and 57, paragraph [0034]), paragraph [0051], paragraphs [0052], [0055] and [0056], [059], [0060], page 69, Table 3, pages 71-72, Table 4, paragraphs [00309-00315], [00325], [00328]-[00333], [00342]-[00350], [00352], [00354]-[00357], [00359]-[00361] are all missing sequence identifiers. Also “CXPXR” in paragraph [00420] is a fully-defined sequence because “X” is serine, threonine, alanine or glycine, and thus “CXPXR” requires a sequence identifier.
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 43, 44, 47, 48, 51, 52, 55, 56, 59, 60 and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Van Berkel et al (WO2017/020972) in view of Drake et al (Bioconjugate Chemistry, 2014, Vol. 25, pp. 1331-1341, reference of the IDS filed 1/26/2024).
Van Berkel et al teach antibody-drug conjugates comprising anti-CD25 antibodies for treating disorders characterized by the presence of CD25+ve cells (abstract). Van Berkel et al teach that Daclizumab is an anti-CD25 antibody of the invention (page 125, lines 5-6) which meets the limitations of claim 66.
Van Berkel et al teach that the anti-CD25 antibody is conjugated to the linker-drug through the reaction of the linker with a cysteine thiol, or the N-terminus of lysine on the antibody to form a bond with a functional group of the linker or spacer (page 35, lines 20-24).
Van Berkel et al do not teach an anti-CD25 antibody comprising a formyl glycine residue.
Drake et al teach the insertion of a recognition sequence for formyl glycine enzyme at the C-terminus of an antibody heavy chain (abstract figure and figure 1B, ). Drake et al teach that the recognition sequence is “CXPXR” wherein X is usually S, T, A or G (page 1332, bridging sentence) thus meeting the limitations of claim 44 wherein Z20 is proline, Z30 is a basic amino acid sequence Arg and X1, X2 and X3, wherein X1, X2 and X3 are any amino acid. Drake et al also teach the insertion of the recognition sequence in the CH1 Domain of the heavy chain bordering A165 and G169 (Tag C) and the light chain bordering A153 and Q 155 (Tag LC) in addition to the C-terminus of the heavy chain (Tag G) resulted in low levels of aggregation (Table 1). Drake et al teach the insertion of the FGE in the CH2 portion of trastuzumab bordering on N544 and A349 (page 1333, Table 1) also provided an antibody having low levels of aggregation
Drake et al teach that Trastuzumab antibodies comprising said Tag C, Tag G (also referred to as CT Tag) and Tag-LC were recombinantly expressed in cells overexpressing human FGE resulting in 86%, 92% and 98% conversion of Cys to Fgly at the LC, CH1 and C-terminus tag sites, respectively (page 1333, lines 1-4 under the heading “Site-Specific Conjugation of a cytotoxic Payload…). Drake et al tach that the modified antibodies comprising the FGly were reacted with a linker drug HIPS-Glu-PEG2-maytansine (page 1333, lines 8-10 under the heading “Site-Specific Conjugation of a cytotoxic Payload…). Drake et al teach that the reactions were high-yielding with <90% conjugation efficiency at the CH1 (Tag C) and C-terminus tag sites (Tag G) and 75% conjugation efficiency at the LC Tag site (page 1334, first column, lines 3-5). Drake et al teach that the LC-, CH1- and CT-tagged ADCs demonstrate potent activity against tumor targets in vitro and in vivo (page 1136, under the heading that states the same). Drake et al teach that the C-terminus tagged ADC conferred the largest survival benefit to tumor bearing mice and also had the longest half-life (page 1337, first column, lines 3-7) relative to αHer2-DM1.
It would have been prima facie obvious at the time prior to the effective filing date to link the pyrrolobenzono diazapines of Van Berkel to the anti-CD25 antibody, Daclizumab through recombinant production of a modified daclizumab comprising of formylglycine enzyme consensus sequence in the CH1 region of the heavy chain bordering on the residues corresponding to A165 and G169 in trastuzumab, in the CH2 region bordering on the residues corresponding to N544 and A349 of trastuzumab, in the LC region bordering on the residues A153 and Q155 of trastuzumab and at the C-terminus of the heavy chain at residue K478.
One of skill in the art would haver been motivated to do so because Drake et al teach that conjugates formed from reaction with the FGly result in stable C-C bonds between the antibody and the toxic payload, and the conjugates formed using trastuzumab. Placing the consensus sequence motifs in the corresponding regions of Daclizumab meet the limitations of claim 48, having the sequence is X1(FGly)X2Z20X3Z30, wherein, according to Drake et al, the sequence is CXPXR with X usually S, T, A or G, and meeting the requirement for Z20 to be proline, Z30 to be the basic amino acid, arginine. Inserting of this sequence at the C-terminus of the heavy chain meets the limitation of the sequence being C-terminal to SLSLSPG:
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEYNQKF
KDKATITADESTNT A YMELSSLRSEDTA VYYCARGGGVFDYWGQGTTLTVSSGPSVFPLAPSSKST
SGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 7, as evidenced by WO2014/055370, page 30) thus fulfilling the limitations of claim 48.
Inserting of the FGE consensus sequence into the light chain of daclizumab bordering on residues corresponding to residues A153 and Q155 of trastuzumab meets the limitation of claim 52 for the sequence being X1(FGly)X2Z20X3Z30, wherein, according to Drake et al, the sequence is CXPXR with X usually S, T, A or G, meeting the requirement for Z20 to be proline, Z30 to be the basic amino acid, arginine, with the insertion of the sequence at the corresponding location bordered by residues A153 and Q155 results in the sequence being C-terminal to KVDNAL and N-terminal to QSGNSQ:
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPARFSGSGSG
TEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLL
NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNR
(SEQ ID NO: 8, as evidenced by WO2014/055370, page 30) thus fulfilling the limitations of claim 52.
Inserting of the FGE consensus sequence into the heavy chain CH1 region of daclizumab bordering on residues corresponding to residues A165 and G169 of trastuzumab meets the limitation of claim 56 for the sequence being X1(FGly)X2Z20X3Z30, wherein, according to Drake et al, the sequence is CXPXR with X usually S, T, A or G, meeting the requirement for Z20 to be proline, Z30 to be the basic amino acid, arginine, with the insertion of the sequence at the corresponding location bordered by residues A165 and G169 results in the sequence being C-terminal to SWNSGA and N-terminal to GVHTFP:
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEYNQKF
KDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 7, as evidenced by WO2014/055370, page 30) thus fulfilling the limitations of claim 56.
Drake et al also teach the insertion of the FGE consensus sequence into the CH2 region of trastuzumab at residues bordering N544 and A349 resulted in a low level of aggregation (page 1333, Table 1).
Thus, it would have been prima facie obvious to use the corresponding location in daclizumab for insertion of the FGE consensus sequence and the production of the formyl glycine in the corresponding region in daclizumab, thus rendering obvious instant claim 59..
Drake et al teach the insertion of the FGE consensus sequence into the CH3 region of trastuzumab resulted in an antibody prone to aggregation (page 1333, Table 1). However, it would have been prima facie obvious to determine if the insertion of the FGE consensus sequence into the corresponding location in Daclizumab resulted in the same tendency toward aggregation as observed in trastuzumab, thus rendering obvious claim 60.
Claims 43, 44-59, 60 and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Van Berkel et al and Drake et al as applied to claims 43, 44, 47, 48, 51, 52, 55, 56, 59, 60 and 66 above, and further in view of Kim et al (WO2018/169953).
Van Berkel et al and Drake et al render obvious the instant claims, including specific teachings regarding the location for insertion of the FGE consensus sequence, and the consensus sequence of “CXPXR”, wherein X can be any amino acid, but is usually serine, threonine, alanine or glycine. Neither Van Berkel et al, nor Drake et al teach the specific Tag sequences used for “CXPXR”.
Kim et al teach the tag sequence of LCTPSR (SEQ ID NO: 561), (paragraph [0010] which is converted to L(fGly)TPSR (SEQ ID NO: 630), (paragraph [0012]) by a formyl glycine generating enzyme (abstract) to produce a fGly-modified heavy chain . Kim et al teach that the formyl glycine tag can be covalently and site-specifically bound to a moiety of interest to produce an antibody conjugate (abstract).
It would have been prima facie obvious to insert the LCTPSR sequence as the “CXPXR” sequence between the residues corresponding to daclizumab heavy chain relative to trastuzumab One of skill in the art would have been motivated to do so by the teachings of Kim et al on using the FGE consensus sequence to produce a formyl glycine modified heavy chain, where the formyl glycine residue is further relied on to produce an antibody conjugate. It also would be obvious to use the same sequence between the residues corresponding to daclizumab light chain. Relative to trastuzumab One of skill in the art would understand that the formyl glycine generating enzyme would also be active on the same consensus sequence in the light chain. Providing the LCTPSR sequence meets the limitation of claim 45 for L(fGly)TPSR because the FGE converts the cysteine to formyl glycine and also meets the limitations of claim 46 for Z30 being R, X1 being L, X2 being T and X3 being S in claim 46. Providing the LCTPSR sequence meets the limitations of claim 49, wherein the LCTPSR is inserted between SPGS and GS in claim 49, and claim 50 for Z30 being R, X1 being L, X2 being T and X3 being S. Providing the LCTPSR sequence meets the limitations of claim53, wherein the LCTPSR is inserted between the KVDNAL and QSGSQ, and claim 54 for Z30 being R, X1 being L, X2 being T and X3 being S. Providing the LCTPSR sequence meets the limitations of claim 57 , wherein the LCTPSR is inserted between SWNSGA and GVHTFP, and claim 58 for Z30 being R, X1 being L, X2 being T and X3 being S.
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 43-50, 65 and 66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,857,637. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claims.
Claim 1 of the patent discloses that the C-terminus of the heavy chain of an anti-CD25 antibody comprises formula II, wherein fGly is the amino acid coupled to the linker. Claim 7 discloses that the sequence of formula II is LfGlyTPSR which meets the limitations of claim 43 for an anti-CD25 antibody comprising a formyl glycine residue, claims 44, 46 and 50 for formula II wherein X1 is L, X2 is T, Z20 is P, X3 is S and Z30 is R, claim 45 for the L(Gly)TPSR sequence, the sequence being at the C-terminus of the heavy chain in claim 47. Claim 9 of the patent discloses that the formula II sequence is C-terminal to SLSLSPG which meets the limitations of claim 48. Claim 10 of the paten discloses that the heavy chain constant region comprises SPGSL(fGly)TPSRGS, which meets the limitations of claim 49. Claim 1 of the patent discloses the anti-CD25 antibody comprising the heavy chain CDRs of SEQ ID NO: 6, 7 and 8, and the light chain CDRs of SEQ ID NO: 9, 10 and 11 which meet the limitation of claim 65. Claim 12 of the patent discloses that the anti-CD25 antibody is daclizumab, which meets the limitations of claim 66.
It is noted that claim 65 reads on the heavy chain of daclizumab (WO2014/055370, Table 7, SEQ ID NO:5):
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEYNQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSS
but only CDR1 of the light chain is the same as the CDR1 in the light chain of daclizumab (WO2014/055370, Table 7, SEQ ID NO: 6):
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPARFSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKR
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/ Primary Examiner, Art Unit 1643
