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 .
DETAILED ACTION
Applicant’s response filed on 10/02/2025 is duly acknowledged.
Claims 5, 6, 11 and 12 have been canceled by the applicants.
Claims 1-4, 7-10 and 13-18, as amended, are currently pending in this application.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-4, 17 and 18; directed to “A mutant of an immunoglobulin-degrading enzyme IdeE…” and Kits) in the reply filed on 10/02/2025 (see REM pages 6-7) is acknowledged. The traversal is on the ground(s) that “a search of all groups would not present an undue burden on the office..”. This is not found persuasive because search for a nucleotide or mutant thereof would not necessarily provide a pertinent prior art applicable for an enzyme protein, or composition/kit therefor.
However, considering applicant’s amendment of claim 10, as currently presented and cancellation of claims 11-12 (see also applicant’s REM, page 7), the invention of group III has been rejoined with Group I, and will be examined hereinafter. However, the election/restriction for group II is still maintained, and would not be rejoined.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-9 (non-elected Group II) have been withdrawn.
Claims 1-4, 10 and 13-18 (elected Group I and rejoined Group III; directed to “A mutant of an immunoglobulin-degrading enzyme IdeE…”, compositions, and Kits comprising the same), as currently amended have been examined on their merits in this action hereinafter.
Priority
This application is a 371 of PCT/CN2021/100844 (filed on 06/18/2021), which claims foreign priority from a Chinese application CN 202010557830.X (filed on 06/18/2020).
Claims
The mutants of immunoglobulin-degrading enzyme IdeE have been interpreted to the extent of the particular amino acid sequences recited in the claims. Kit claims have been interpreted as comprising specific product components as recited in the claims.
Claim Objections
Claims 16-18 (as presented) are objected to because of the following informalities: Claims 16, 17 and 18, each recite the limitation in abbreviated form “FcRn” (see claim 16, line 3; claim 17, section (4); claim 18, last line), which should be recited in full form (for instance “neonatal Fc receptor (FcRn)”) at least the first time it appears in a claim set. The specification should also be amended to reflect such change. 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 2, 14-16 and 18 (as presented) 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 (section (2)) recites the broad recitation of limitations “deletion of the first 15, the first 16, the first 17, the first 18 or the first 19 amino acids at the N-terminus of the immunoglobulin-degrading enzyme IdeE”, and the claim also recites “preferably the first 18 amino acids”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim.
Similarly, claim 2, section (3) also recites both broad limitations “deletion of the last 5 or the last 10 amino acids at the C-terminus of the immunoglobulin-degrading enzyme IdeE”, and narrow limitations ”preferably the first 18 amino acids”, which renders the claim indefinite for the same reasons as discussed above. Appropriate correction is required.
Likewise, Claim 15 recites the broad recitation of limitations “a viral vector drug”, and the claim also recites “preferably selected from the group consisting of: an oncolytic virus, a gene therapy virus and a viral vector vaccine”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim. Appropriate correction is required.
Also, Claim 16 recites the broad recitation of limitations “an agent capable of reducing the IgG level in the blood”, and the claim also recites “preferably selected from the group consisting of: an FcRn antibody and an Fc fragment variant with a high affinity to FcRn”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim. Appropriate correction is required.
Claim 18 has been reproduced as follows:
“18. (Previously Presented) A kit, comprising: a part A and a part B, wherein
the part A comprises the mutant according to claim 1, and
the part B comprises one or more selected from the group consisting of:
(1) a pharmaceutically acceptable carrier or excipient; (2) an antibody or an Fc-containing protein; and/or (3) a viral vector drug; and/or (4) an agent capable of reducing the IgG level in the blood;
wherein the viral vector drug is selected from an oncolytic virus, a gene therapy virus and a viral vector vaccine; and the agent capable of reducing the IgG level in the blood is selected from an FcRn antibody and an Fc fragment variant with a high affinity to FcRn.”
From the recitation of claim 18, it appears that applicants intend to recite a Markush group in part B, the proper recitation of which should be in the form of “selected from the group consisting of A, B, C, and D”, for instance. However, the recitations of “and/or between the alternative components as presented raise ambiguity and confusion as to whether the components recited after “and/or” are actually required, or optional components of the kit product as claimed. The metes and bounds of the claimed invention is therefore not properly defined. Appropriate correction is required.
Claim 14 (as presented) is recites the limitation "the antibody target" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 14 directly depends from claim 13 (which in turn depends from claim 10) that does not provide a reasonable basis for “an antibody target” per se. Appropriate correction is required.
NOTICE: 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 10, 17 and 18 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lannergard et al (2006; cited in IDS dated 06/22/2023; citation # 8).
Claim 1 has been reproduced below:
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Lannergard et al (2006) disclose the mutant immunoglobulin-degrading enzyme (and composition thereof in pharmaceutically acceptable carrier such as phosphate buffered saline, PBS; taken herein as a kit comprising the mutant protein in carrier/buffer; see Title, page 231, section “IgG-cleavage assay”, for instance) comprising isolated/purified protein; wherein (regarding instant claims 1-2) the mutant immunoglobulin-degrading enzyme protein comprises four different amino acid substitutions T8A, A10V, A59V and R280G (see p. 232, left column, 1st and 2nd paragraphs, for instance) as shown in the amino acid sequence homology with 98.8% identity to SEQ ID NO: 2 of instant claim 1 as reproduced below:
SEQ ID NO: 2
(UNIPROT DATABASE RESULT- T8A, A10V, A59V, R280G substitutions)
RESULT 6
Q0PIW1_STRSZ
ID Q0PIW1_STRSZ Unreviewed; 349 AA.
AC Q0PIW1;
DT 05-SEP-2006, integrated into UniProtKB/TrEMBL.
DT 05-SEP-2006, sequence version 1.
DT 02-APR-2025, entry version 30.
DE SubName: Full=IgG endopeptidase {ECO:0000313|EMBL:ABH04315.1};
GN Name=ideZ {ECO:0000313|EMBL:ABH04315.1};
OS Streptococcus equi subsp. zooepidemicus.
OC Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=40041 {ECO:0000313|EMBL:ABH04315.1};
RN [1] {ECO:0000313|EMBL:ABH04315.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=ZV {ECO:0000313|EMBL:ABH04315.1};
RX PubMed=16923080; DOI=10.1111/j.1574-6968.2006.00404.x;
RA Lannergard J., Guss B.;
RT "IdeE, an IgG-endopeptidase of Streptococcus equi ssp. equi.";
RL FEMS Microbiol. Lett. 262:230-235(2006).
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DR EMBL; DQ826037; ABH04315.1; -; Genomic_DNA.
DR RefSeq; WP_231194787.1; NZ_JAHLHM010000004.1.
DR AlphaFoldDB; Q0PIW1; -.
DR MEROPS; C66.001; -.
DR GO; GO:0008233; F:peptidase activity; IEA:InterPro.
DR Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR InterPro; IPR015117; IdeS.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR Pfam; PF09028; Mac-1; 1.
DR SUPFAM; SSF54001; Cysteine proteinases; 1.
PE 4: Predicted;
KW Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..34
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 35..349
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5004175543"
FT DOMAIN 43..345
FT /note="Ig protease IdeS"
FT /evidence="ECO:0000259|Pfam:PF09028"
SQ SEQUENCE 349 AA; 39036 MW; 1D01DEEB16FE985C CRC64;
Query Match 98.8%; Score 1642; Length 349;
Best Local Similarity 98.7%;
Matches 311; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 1 DDYQRNATEAYAKEVPHQITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKAF 60
||||||| | |||||||||||||||||||||||||||||||||||||||||||||||| |
Db 35 DDYQRNAAEVYAKEVPHQITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKVF 94
Qy 61 DGKDNLLCGAATAGNMLHWWFDQNKTEIEAYLSKHPEKQKIIFNNQELFDLKAAIDTKDS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 95 DGKDNLLCGAATAGNMLHWWFDQNKTEIEAYLSKHPEKQKIIFNNQELFDLKAAIDTKDS 154
Qy 121 QTNSQLFNYFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 155 QTNSQLFNYFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKR 214
Qy 181 GGIFDAVFTRGDQTTLLTARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 215 GGIFDAVFTRGDQTTLLTARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVI 274
Qy 241 NLWGADFNAEGNLEAIYVTDSDANASIGMKKYFVGINAHRHVAISAKKIEGENIGAQVLG 300
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||
Db 275 NLWGADFNAEGNLEAIYVTDSDANASIGMKKYFVGINAHGHVAISAKKIEGENIGAQVLG 334
Qy 301 LFTLSSGKDIWQKLS 315
|||||||||||||||
Db 335 LFTLSSGKDIWQKLS 349
Regarding instant claim 3 section (4), the disclosed mutant enzyme protein comprises substitution A59V (i.e. comprising the substitution as set forth in the instant amino acid sequence SEQ ID NO: 14). Since, Lannergard et al disclose the mutant enzyme protein as discussed above in a carrier such as PBS (taken herein as pharmaceutically acceptable “carrier or excipient”, as components of a kit product, for instance), in the absence of any specific definition from applicants (see SPEC p. 9, section “II. Pharmaceutical combinations”) the limitations of instant claims 10, 17 and 18 as presented are deemed met by the cited prior art reference. Also, since the immunoglobulin-degrading enzyme comprising one or more of the same substitution(s) in the protein have already been disclosed, the functional property as recited in instant claim 1 (i.e. higher activity and/or higher thermal stability), in the absence of any specific conditions recited in the claims, would be deemed inherent to the enzyme as disclosed by the cited prior art.
Claims 1-3, 10, 17 and 18 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kjellman et al (WO 2016/128559 A1; cited in IDS dated 10/02/2025; for citation # 2).
Kjellman et al (2016), while teaching cysteine proteases displaying IgG degrading activity, and uses thereof in treatment or prevention of diseases or conditions mediated by IgG (see Title, Abstract, and disclosure on p.3), disclose (regarding instant claims 1-3) the mutant immunoglobulin-degrading enzyme proteins that have one or more amino acid substitutions, including the mutant R280G having 99.6% sequence identity over 315 amino acids of instant SEQ ID NO: 2 of claim 1, disclosed as SEQ ID NO: 4 by Kjellman et al (see p.23, and sequence homology as reproduced below).
SEQ ID NO: 2 (A_GeneSeq database - R280G substitution)
RESULT 22
BDD63256
(NOTE: this sequence has 18 duplicates in the database searched.
See complete list at the end of this report)
ID BDD63256 standard; protein; 315 AA.
XX
AC BDD63256;
XX
DT 06-OCT-2016 (first entry)
XX
DE Streptococcus pyogenes IdeS protein, SEQ ID 4.
XX
KW IdeS protein; addisons disease; antiinflammatory; autoimmune disease;
KW autoimmune hepatitis; celiac disease; dermatological; endocrine-gen.;
KW gastrointestinal-gen.; hematological-gen.; hepatotropic;
KW immunosuppressive; neutropenia; pemphigoid; prophylactic to disease;
KW protein cleavage; protein therapy; therapeutic; urticaria.
XX
OS Streptococcus pyogenes.
XX
CC PN WO2016128559-A1.
XX
CC PD 18-AUG-2016.
XX
CC PF 12-FEB-2016; 2016WO-EP053054.
XX
PR 12-FEB-2015; 2015GB-00002305.
XX
CC PA (HANS-) HANSA MEDICAL AB.
XX
CC PI Kjellman C, Jarnum S, Nordahl E;
XX
DR WPI; 2016-50236S/59.
XX
CC PT New polypeptide useful in composition for preventing and/or treating
CC PT disease e.g. Addisons disease, autoimmune hepatitis, autoimmune
CC PT neutropenia, and bullous pemphigoid, comprises variant comprising
CC PT specific amino acid sequence.
XX
CC PS Claim 1; SEQ ID NO 4; 91pp; English.
XX
CC The present invention relates to a novel polypeptide useful in a
CC composition for preventing and/or treating diseases. The invention
CC further relates to: (1) a polynucleotide or expression vector comprising
CC nucleic acid sequence encoding polypeptide; (2) a host cell comprises the
CC polynucleotide or expression vector; (3) a composition comprises the
CC above-mentioned polypeptide and carrier or diluents; (4) a method for
CC preventing or treating disease or condition in a subject; and (5) a
CC method for cleaving IgG. The diseases are selected from Addison's
CC disease, autoimmune hepatitis, autoimmune neutropenia, bullous
CC pemphigoid, celiac disease, and chronic urticaria. The present sequence
CC is a Streptococcus pyogenes IdeS protein, used in the composition of the
CC invention for preventing and/or treating diseases.
XX
SQ Sequence 315 AA;
Query Match 99.6%; Score 1655; Length 315;
Best Local Similarity 99.7%;
Matches 314; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 DDYQRNATEAYAKEVPHQITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKAF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DDYQRNATEAYAKEVPHQITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKAF 60
Qy 61 DGKDNLLCGAATAGNMLHWWFDQNKTEIEAYLSKHPEKQKIIFNNQELFDLKAAIDTKDS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DGKDNLLCGAATAGNMLHWWFDQNKTEIEAYLSKHPEKQKIIFNNQELFDLKAAIDTKDS 120
Qy 121 QTNSQLFNYFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QTNSQLFNYFRDKAFPNLSARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKR 180
Qy 181 GGIFDAVFTRGDQTTLLTARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGIFDAVFTRGDQTTLLTARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVI 240
Qy 241 NLWGADFNAEGNLEAIYVTDSDANASIGMKKYFVGINAHRHVAISAKKIEGENIGAQVLG 300
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||
Db 241 NLWGADFNAEGNLEAIYVTDSDANASIGMKKYFVGINAHGHVAISAKKIEGENIGAQVLG 300
Qy 301 LFTLSSGKDIWQKLS 315
|||||||||||||||
Db 301 LFTLSSGKDIWQKLS 315
In addition, Kjellman et al also disclose the mutant immunoglobulin-degrading enzyme protein comprising substitution at amino acid 59, as A59T (alanine to threonine change), which is in addition to substitution R280G, designated as SEQ ID NO: 7 (pCART 198) (see Kjellman et al, p. 23) that also has a polypeptide length of 315 amino acids. Kjellman et al disclose various substitutions with the aim of increasing efficacy of cleavage of human IgG (see p. 54, 3rd paragraph; and p. 58, 1st paragraph, for instance) that would help improve therapeutic potential of said immunoglobulin-degrading enzyme proteins, without significant increase in their immunogenicity (Abstract and Summary of the invention, p.3). Kjellman et al disclose (regarding instant claims 10, 17 and 18) the composition comprising mutant polypeptides in suitable carriers, diluents such as PBS, or other excipients (taken herein as kit components; see p. 28, lines 24-25, and section “Compositions and formulations comprising polypeptides”; and p. 53, section “Visualisation of IgG cleavage patterns”, for instance). Since the immunoglobulin-degrading enzyme comprising one or more of the same substitution(s) in the protein have already been disclosed, the functional property as recited in instant claim 1 (i.e. higher activity and/or higher thermal stability), in the absence of any specific conditions recited in the claims, would be deemed inherent to the mutant enzyme as disclosed by the cited prior art.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
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.
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, 10 and 13-18 (as currently presented) are rejected under 35 U.S.C. 103 as being unpatentable over Kjellman et al (WO 2016/128559 A1; cited in IDS dated 10/02/2025; for citation # 2) taken with Lannergard et al (2006; cited in IDS dated 06/22/2023; citation # 8) and Blumberg et al (2019; NPL cited as ref. [U] on PTO 892 form)
Claims 1 and 13-16 as presented by applicants, have been reproduced as follows:
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The detailed teachings and/or suggestion from Kjellman et al in combination with the disclosure from Lannergard et al as they pertain to instant claims 1-4, 10, 17 and 18, have been discussed above, and are further relied upon in the same manner hereinafter.
It is to be noted that Kjellman et al disclose therapeutic composition (regarding instant claims 10, 13-15) comprising mutant immunoglobulin-degrading enzyme proteins further comprising an antibody to treat cancer or another diseases associated with pathogenic IgG antibodies (see p. 32, Table D; and disclosure on p. 34 and 37, for instance), wherein the antibody targets are disclosed as comprising variety of tumor antigens, cytokines, hormones, intracellular messenger, etc. (see Kjellman et al, p. 37, 3rd paragraph, for instance); wherein compositions for therapeutic use may further comprise a viral vector for gene therapy application in a subject in need, and Kits for carrying out the methods for use in such therapeutic treatments (see Kjellman et al, p. 6, lines 1-3; and p. 6, line 10, for instance).
As discussed above, Lannergard et al disclose mutant IgG-degrading enzyme protein that comprises substitution A59V (regarding instant claims 3-4), corresponding to the mutant as set forth in the instant amino acid sequence SEQ ID NO: 14. Since, Kjellman et al disclose various substitutions with the aim of increasing efficacy of cleavage of human IgG (see p. 54, 3rd paragraph; and p. 58, 1st paragraph, for instance) that would help improve therapeutic potential of said immunoglobulin-degrading enzyme proteins, without significant increase in their immunogenicity (Abstract and Summary of the invention, p.3), such substitutions that help increase IgG cleavage activity of mutant IgG-degrading enzyme proteins, would have been obvious to an artisan of ordinary skill in the art given the combined disclosure from Kjellman et al when taken with Lannergard et al, as discussed above.
However, the composition comprising mutant immunoglobulin-degrading enzyme proteins further comprising “an agent capable of reducing the IgG level in the blood” (see instant claim 16), has not been specifically disclosed and/or exemplified by the combined teachings from Kjellman et al when taken with Lannergard et al, as discussed above.
Blumberg et al (2019) disclose the fact that blocking neonatal crystallizable fragment receptor (FcRN; see Title, Abstract, and Introduction on p. 1) in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses, which demonstrates the role of FcRn in controlling not only IgG protection from catabolism, but also inflammatory pathways associated with IgG immune complexes (IgG-ICs) that are known to be involved in a variety of autoimmune diseases. Since FcRn functions broadly in inflammatory pathways by preventing the degradation of IgG and IgG-ICs and enabling IgG-ICs to mediate innate and adaptive immune functions, an agent that helps in reducing the levels of IgG in blood would be therapeutic in patients in need, especially in patients with autoimmune disorders (see entire disclosure in “Introduction” on p. 1, for instance). Blumberg et al disclose lowering of circulating IgG levels in mice, primates and human subjects using a FcRn-blocking, humanized monoclonal antibody, SYNT001 (see Abstract on p. 1, for instance), which was found to significantly reduce the blood levels of all IgG subtypes and IgG-ICs by binding to FcRn (see Blumberg et al, p. 2, Table 1; and p. 8, section “Discussion”, for instance), as well as was found to be clinically safe for use in humans (see p. 3, section “Clinical study of SYNT001”, and Figs. 3-4, for instance), which suggested potential utility of SYNT001 in the treatment of autoimmune disease by decreasing pathogenic autoantibody levels in blood of subjects in need thereof.
Thus, to a person of ordinary skill in the art, it would have been obvious to include one or more agent(s) in combination with the composition disclosed by the combined teachings from Kjellman et al when taken with Lannergard et al, comprising mutant immunoglobulin degrading enzymes in order to effectively employ said modified therapeutic composition for use in subjects having autoimmune disorders or pathologies associated with IgG, as successfully demonstrated by Blumberg et al, wherein the levels of circulating IgG and complexes thereof are significantly reduced in order to help effectively treat the said patients in need. Since, Blumberg et al already disclose the fact that SYNT001 monoclonal antibody binds with high affinity to FcRN, and is highly effective in reducing the levels of IgG in circulation of treated subjects, an artisan of ordinary skill in the art would have been highly motivated and successful in such combination with the composition of mutant immunoglobulin degrading enzymes as disclosed by the combined teachings and/or suggestions from Kjellman et al when taken with the disclosure from Lannergard et al in view of teachings from Blumberg et al, as discussed above.
In addition, since, Kjellman et al already disclose the therapeutic compositions comprising various mutant immunoglobulin-degrading enzyme proteins in combination with agents including antibody to various therapeutic targets (including targets such as cancer/tumor antigens, cytokines, etc.; see discussion above) and for prevention and treatment of autoimmune disorders associated with IgG, such modification in order to reduce the levels of pathogenic IgG in circulation using monoclonal antibody (as taught by Blumberg et al, above) would have been clearly obvious and/or fully contemplated by an artisan of ordinary skill in the art, unless evidence and/or data provided on record to the contrary (which is currently lacking on record; see instant specification, Examples 1-13).
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as claimed.
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.
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Claim 1 (as presented) is rejected on the ground of nonstatutory double patenting as being unpatentable over at least claim 1 of U.S. Patent No. 12,319,942 B2 (issued on June 3, 2025 to common inventors and assignee). Although the claims at issue are not identical, they are not patentably distinct from each other because issued claim 1 of patent ‘942 is also directed to a mutant of immunoglobulin-degrading enzyme as reproduced herein below:
“1. A mutant of an immunoglobulin degrading enzyme IdeE, wherein an amino acid sequence of the immunoglobulin degrading enzyme IdeE is shown as SEQ ID NO: 2:
the mutant comprises a mutation of a truncation of the immunoglobulin degrading enzyme IdeE, by deleting the sequence of the first 15, the first 16, the first 17, the first 18 or the first 19 amino acids at the N-terminus; and
the mutant comprises the amino acid sequence shown as SEQ ID NO: 36.”
It is noted that the SEQ ID NO: 36 represents 18 amino acid truncation from N-terminus of SEQ ID NO: 2 as reproduced below (see patent’ 942, col. 53-54):
ITSVWTKGVT PLTPEQFRYN NEDVIHAPYL AHQGWYDITK AFDGKDNLLC GAATAGNMLH 60
WWFDQNKTEI EAYLSKHPDK QKIIFNNQEL FDLKAAIDTK DSQTNSQLFN YFRDKAFPNL 120
SARQLGVMPD LVLDMFINGY YLNVFKTQST DVNRPYQDKD KRGGIFDAVF TRGDQTTLLT 180
ARHDLKNKGL NDISTIIKQE LTEGRALALS HTYANVSISH VINLWGADFN AEGNLEAIYV 240
TDSDANASIG MKKYFVGINA HGHVAISAKK IEGENIGAQV LGLFTLSSGK DIWQKLS 297
Since, instant claim 1 (section (2), in particular) as currently recited is also drawn to N-terminal truncations of the same IdeE enzyme protein, including deletions of first 1 to first 19 amino acids from SEQ ID NO: 2, the issued claim 1 represents an anticipatory species of the instantly claimed invention (i.e. genus-species relationship; see instantly claimed 18 amino acid deletion SEQ ID NO: 21, designated as WT_del18; a mutant enzyme protein having 297 amino acids; see instant specification, p. 24, Table 3). Also, since the mutant having the same amino acid sequence would have the same structural-functional properties, the species disclosed in the issued ‘942 patent would be deemed anticipatory to the instant claim 1 as currently presented. Therefore an ODP rejection is deemed proper.
Claim 13 (as currently presented) is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1, 2 and 4 of co-pending Application No. 18/027,755 (reference application ; filed in US on 05/05/2023 by same inventors and assignee). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the co-pending application ‘755 is also directed to product comprising an immunoglobulin-degrading enzyme (such as IdeE, IdeS, IdeZ; see co-pending claim 2) that is IgG cysteine protease, or variants thereof- as reproduced below:
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91
714
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Since, claim 13 of the instant application also requires one or more variant(s) of an immunoglobulin-degrading enzyme IdeE, in a composition that further comprises a carrier and an Fc-containing protein- such as an antibody, the scope of the two sets of claims are clearly overlapping in a genus-species relationship, and therefore an ODP rejection is deemed proper.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657