DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 01/19/2026 in response to the Non-Final Rejection mailed on 10/17/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claim 2 is cancelled.
4. New claim 19 is added.
5. Claims 1 and 3-19 are pending.
6. Applicant’s remarks filed on 01/19/2026 in response to the Non-Final Rejection mailed on 10/17/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Priority
7. Acknowledgement is made of applicants’ filing of the certified translation of the foreign priority application, filed on 01/19/2026.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claim 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for indefiniteness is withdrawn in view of applicants’ amendment to the claims to cancel claim 2.
Claim Rejections - 35 USC § 103
9. The rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO 2021/254479 A1; cited on IDS filed on 08/20/2025 with US Patent Application Publication 2023/0364207 A1 serving as a translation, cited on PTO-892 mailed on 10/17/2025) in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025) is withdrawn in view of applicants’ amendment to the claims to cancel claim 2.
10. The rejection of claims 1 and 3-18 under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO 2021/254479 A1; cited on IDS filed on 08/20/2025 with US Patent Application Publication 2023/0364207 A1 serving as a translation, cited on PTO-892 mailed on 10/17/2025) in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to incorporate new claim 19, which is necessitated by applicants’ amendment to the claims to add new claim 19.
Claims 1 and 3-19 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO 2021/254479 A1; cited on IDS filed on 08/20/2025 with US Patent Application Publication 2023/0364207 A1 serving as a translation, cited on PTO-892 mailed on 10/17/2025) in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025).
11. With respect to claim 1, Liu et al. teach a mutant immunoglobulin degrading enzyme comprising a mutation at least one of the positions 8, 10, 24, 59, 97, and 280 of an amino acid sequence that is 98.9% identical to SEQ ID NO: 2 wherein the first 19 amino acid residues of the N-terminus of the amino acid sequence are truncated and the enzyme is intracellularly expressed [see Abstract; paragraphs 0029-0032; 0069; alignment attached as APPENDIX A]. The 19 residue truncation of Liu et al. corresponds to the first amino acid of present SEQ ID NO: 2. It is noted that the amino acid at position 97 corresponds to an aspartic acid in SEQ ID NO: 2 and Liu et al. teach that the amino acid at position 97 can be an aspartic acid [see paragraph 0048].
With respect to claim 2, Liu et al. teach the immunoglobulin-degrading enzyme wherein the enzyme is derived from Streptococcus equi ssp. equi [see paragraph 0005].
With respect to claim 7, Liu et al. teach a nucleotide sequence encoding the immunoglobulin degrading enzyme having one or more nucleotide substitutions, additions, and/or deletions compared with SEQ ID NO: 3 [see paragraph 0012; alignment attached as APPENDIX B].
With respect to claim 8, Liu et al. teach an expression vector comprising the nucleotide sequence encoding the immunoglobulin degrading enzyme [see paragraph 0012].
With respect to claim 9, Liu et al. teach a host cell comprising the nucleotide sequence encoding the immunoglobulin degrading enzyme [see paragraph 0012].
With respect to claim 10, Liu et al. teach the host cell wherein the host cell is a bacterial cell or a fungal cell [see paragraph 0067].
With respect to claim 11, Liu et al. teach the host cell wherein the bacterial cell is an Escherichia coli cell or the fungal cell is a yeast cell [see paragraph 0067].
With respect to claim 12, Liu et al. teach a method for intracellular expression of the immunoglobulin degrading enzyme including the steps of selecting a single colony of a host cell, culturing a seed culture, culturing the seed culture in a fermenter, inducing expression of the immunoglobulin-degrading enzyme and collecting the immunoglobulin-degrading enzyme wherein the host cell comprises a nucleotide sequence encoding the immunoglobulin degrading enzyme having at least 85% identity to SEQ ID NO: 3 [see paragraphs 0012, 0130; alignment attached as APPENDIX B].
With respect to claim 13, Liu et al. teach a composition comprising the immunoglobulin-degrading enzyme and a pharmaceutically acceptable carrier or excipient [see paragraphs 0006-0013].
With respect to claim 14, Liu et al. teach the composition comprising an antibody or protein comprising an Fc fragment, wherein a target of the antibody cell surface protein, a cytokine, a hormone, an enzyme, an intracellular messenger, an intercellular messenger, and an immune checkpoint inhibitor [see paragraph 0069].
With respect to claim 15, Liu et al. teach the composition comprising a viral vector drug and/or a drug configured for reducing a blood IgG level [see paragraph 0069].
With respect to claim 16, Liu et al. teach the composition wherein the viral vector drug is an oncolytic virus, a gene therapy, a viral vector vaccine and the drug configured for reducing the blood IgG level is selected from the following an FcRn antibody and an Fc fragment variant with high affinity for FcRn [see paragraph 0069].
With respect to claim 17, Liu et al. teach a kit comprising the immunoglobulin-degrading enzyme and a pharmaceutically acceptable carrier or excipient [see paragraphs 0006-0013] a viral vector drug and a drug configured for reducing a blood IgG level is selected from the following an FcRn antibody and an Fc fragment variant with high affinity for FcRn [see paragraph 0069].
With respect to claim 18, Liu et al. teach a kit comprising a first and a second kit comprising the immunoglobulin-degrading enzyme and a pharmaceutically acceptable carrier or excipient [see paragraphs 0006-0013] a viral vector drug and a drug configured for reducing a blood IgG level is selected from the following an FcRn antibody and an Fc fragment variant with high affinity for FcRn [see paragraphs 0069 and 0102-0103].
With respect to claim 19, Liu et al. teach a nucleotide sequence encoding the immunoglobulin degrading enzyme [see paragraph 0012].
Although Liu et al. teach a substitution at position 280 which corresponds to a glycine in SEQ ID NO: 2 of the present claims, Liu et al. does not teach wherein the amino acid in this position is glycine. To this end, Siloto et al. teach that techniques such as alanine scanning mutagenesis and site saturation mutagenesis are used to study the function of a single amino acid in relation to the rest of the protein [see Abstract; p. 182, column 1]. Siloto et al. teach that in site saturation mutagenesis involves substitution of a single amino acid to any other 19 possible substituents which provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position [see p. 182, column 1].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Liu et al. and Siloto et al. to use a site saturation mutagenesis strategy in the mutant enzymes of Liu et al. such that all 20 amino acid residues could be represented at a single position for targeted mutagenesis because Liu et al. teach methods to mutate immunoglobulin degrading enzymes to produce a polypeptide of improved activity and stability. Siloto et al. teach that in site saturation mutagenesis involves substitution of a single amino acid to any other 19 possible substituents which provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position. One of ordinary skill in the art desiring to substitute the positions of Liu et al. with the amino acid residue that has the greatest effect on stability and activity would have a reasonable expectation of success, a reasonable level of predictability, and would be motivated to combine the teachings of Liu et al. and Siloto et al. because Siloto et al. acknowledges that site saturation mutagenesis provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 3, wherein the immunoglobulin degrading enzyme does not cause bacterial, fungal or cellular autolysis during expression and claims 4-6 wherein during expression in a bacterial, fungal or cellular host, a OD600 value does not decrease after exceeding 40, 50, 60, 70, or 80, MPEP 2145.II states “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention."). In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990)”.
RESPONSE TO REMARKS: Beginning on p. 7 of applicants’ remarks, applicants in summary contend that the cited documents discloses the sequence with the addition of a methionine residue at the N-terminus, nor do the references appreciate that the addition of the methionine at the N-terminus results in significant increase in expression of IdeE2.
This argument is found to be not persuasive because Liu et al. teach a mutant immunoglobulin degrading enzyme comprising a mutation at least one of the positions 8, 10, 24, 59, 97, and 280 of an amino acid sequence that is 98.9% identical to SEQ ID NO: 2 wherein the first 19 amino acid residues of the N-terminus of the amino acid sequence are truncated and the enzyme is intracellularly expressed. One of ordinary skill in the art is aware that expression of a recombinant protein requires an initiator codon (ATG) in the expression vector that encodes an initiator methionine. As such, the truncated IdeE of Liu et al. would necessarily have such a methionine on its N-terminus. Furthermore, Liu et al. teach in paragraph 0011 that the protein is linked to a secretory signal sequence and/or methionine at the N-terminus.
Double Patenting
12. The provisional nonstatutory double patenting rejection of claim 2 over claims 1-18 of copending Application No. 18/001876 in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025) is withdrawn in view of applicants’ amendment to the claims to cancel claim 2.
13. The provisional nonstatutory double patenting rejection of claims 1 and 3-18 over claims 1-18 of copending Application No. 18/001876 in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to incorporate new claim 19, which is necessitated by applicants’ amendment to the claims to add new claim 19.
Claims 1 and 3-19 are provisionally rejected on the the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/001876 in view of Siloto et al. (Biocatalysis and Agricultural Biotechnology, 2012; cited on PTO-892 mailed on 10/17/2025).
Claims 1-18 of the ‘876 application recite a mutant immunoglobulin-degrading enzyme IdeE, wherein the IdeE comprises or consists of an amino acid sequence as set forth in SEQ ID NO: 2 and the mutant comprises a mutation selected from the group consisting of (1) a substitution of one or more positions 8, 10, 24, 59, 97 and 280 of the amino acid sequence thereby obtaining the mutant; and/or (2) truncation of the IdeE, by deleting the sequence of the first 1, the first 2, the first 3, the first 4, the first 5, the first 6, the first 7, the first 8, the first 9, the first 10, the first 11, the first 12, the first 13, the first 14, the first 15, the first 16, the first 17, the first 18 or the first 19 amino acids at the N-terminus wherein the mutant has higher activity than that of the IdeE and/or has higher thermal stability than that of the IdeE, nucleotides encoding said IdeE, host cells expressing, and compositions comprising said IdeE. It is noted that the amino acid at position 97 corresponds to an aspartic acid in SEQ ID NO: 2 and the disclosure of the ‘876 application teach that the amino acid at position 97 can be an aspartic acid.
Although the ‘876 application recite a substitution at position 280 which corresponds to a glycine in SEQ ID NO: 2 of the present claims, the ‘876 application does not recite wherein the amino acid in this position is a glycine. To this end, Siloto et al. teach that techniques such as alanine scanning mutagenesis and site saturation mutagenesis are used to study the function of a single amino acid in relation to the rest of the protein [see Abstract; p. 182, column 1]. Siloto et al. teach that in site saturation mutagenesis involves substitution of a single amino acid to any other 19 possible substituents which provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position [see p. 182, column 1].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the recitations of the ‘876 application and Siloto et al. to use a site saturation mutagenesis strategy in the mutant enzymes of the ‘876 application such that all 20 amino acid residues could be represented at a single position for targeted mutagenesis because ‘876 recite mutated immunoglobulin degrading enzymes to produce a polypeptide of improved activity and stability. Siloto et al. teach that in site saturation mutagenesis involves substitution of a single amino acid to any other 19 possible substituents which provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position. One of ordinary skill in the art desiring to substitute the positions of ‘876 application with the amino acid residue that has the greatest effect on stability and activity would have a reasonable expectation of success, a reasonable level of predictability, and would be motivated to combine the recitations of the ‘876 application and Siloto et al. because Siloto et al. acknowledges that site saturation mutagenesis provides an advantage that all possible substitutions can be obtained, which allows for a more comprehensive analysis of the function of the original amino acid in the targeted position. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 3, wherein the immunoglobulin degrading enzyme does not cause bacterial, fungal or cellular autolysis during expression and claims 4-6 wherein during expression in a bacterial, fungal or cellular host, a OD600 value does not decrease after exceeding 40, 50, 60, 70, or 80, MPEP 2145.II states “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention."). In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990)”.
This is a provisional nonstatutory double patenting rejection.
RESPONSE TO REMARKS: Beginning on p. 8 of applicants’ remarks, applicants in summary contend that each of the instant claims is not individually compared to a claim in the reference patent, the IdeE2 in the current claims exhibits unexpected expression levels with the sole different being an additional methionine, and features recited in claims 3-6 are not rendered obvious and are materially distinct.
These arguments are found to be not persuasive because the copending claims of the ‘876 application are drawn to IdeE enzymes and nucleotides encoding said enzymes that are not structurally distinct and non-obvious from the claimed enzymes in view of Siloto et al. Regarding the unexpected expression levels with the addition of methionine, the disclosure envisions embodiments encompassed by the claims that contain a methionine at the N-terminus [see p. 3 of the ‘876 disclosure]. MPEP 804.II.B1. states "[t]he specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. V. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC V. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office ('PTO') determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction 'in light of the specification as it would be interpreted by one of ordinary skill in the art.' " Phillips V. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. Of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). in re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "It]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVéie Inc. V. Kennedy Institute of Rreumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. V. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. V. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008): Geneva Pharmaceuticals Inc. V. GlaxoSmithKline PLC. 349 F3d 1373. 1385-86. 68 USPQ2d 1865, 1875 (Fed. Cir. 2003)."
Regarding applicant’s remarks that the examiner is arguing inherency, this argument is found to be not persuasive as the examiner is of the position that the functional limitations recited in claims 3-6 are latent properties that flow from the recitations and teachings of ‘876 application and Siloto et al. The examiner’s position is consistent with MPEP 2145.II.
Conclusion
14. Status of the claims:
Claims 1 and 3-19 are pending.
Claims 1 and 3-19 are rejected.
No claims are in condition for an allowance.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. 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.
/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
APPENDIX A
SEQ ID NO: 2 with Liu et al.
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1554 98.9 315 1 US-18-001-876A-2 MUTANT OF IMMUNOGL
ALIGNMENTS
RESULT 1
US-18-001-876A-2
Query Match 98.9%; Score 1554; DB 1; Length 315;
Best Local Similarity 99.3%;
Matches 295; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 2 ITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKAFDGKDNLLCGAATAGNMLH 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 ITSVWTKGVTPLTPEQFRYNNEDVIHAPYLAHQGWYDITKAFDGKDNLLCGAATAGNMLH 78
Qy 62 WWFDQNKTEIEAYLSKHPDKQKIIFNNQELFDLKAAIDTKDSQTNSQLFNYFRDKAFPNL 121
||||||||||||||||||:|||||||||||||||||||||||||||||||||||||||||
Db 79 WWFDQNKTEIEAYLSKHPEKQKIIFNNQELFDLKAAIDTKDSQTNSQLFNYFRDKAFPNL 138
Qy 122 SARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKRGGIFDAVFTRGDQTTLLT 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 SARQLGVMPDLVLDMFINGYYLNVFKTQSTDVNRPYQDKDKRGGIFDAVFTRGDQTTLLT 198
Qy 182 ARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVINLWGADFNAEGNLEAIYV 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 ARHDLKNKGLNDISTIIKQELTEGRALALSHTYANVSISHVINLWGADFNAEGNLEAIYV 258
Qy 242 TDSDANASIGMKKYFVGINAHGHVAISAKKIEGENIGAQVLGLFTLSSGKDIWQKLS 298
||||||||||||||||||||| |||||||||||||||||||||||||||||||||||
Db 259 TDSDANASIGMKKYFVGINAHRHVAISAKKIEGENIGAQVLGLFTLSSGKDIWQKLS 315
APPENDIX B
SEQ ID NO: 3 with backtranslation of Liu et al.
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 732.6 81.4 891 1 NASEQ2_10142025_153015
ALIGNMENTS
RESULT 1
NASEQ2_10142025_153015
Query Match 81.4%; Score 732.6; DB 1; Length 891;
Best Local Similarity 88.9%;
Matches 792; Conservative 0; Mismatches 99; Indels 0; Gaps 0;
Qy 4 ATCACCAGCGTGTGGACCAAAGGTGTTACCCCGCTGACCCCGGAGCAGTTCCGTTACAAC 63
|| |||||||||||||||||||| || ||||||||||||||||| ||||| || || |||
Db 1 ATTACCAGCGTGTGGACCAAAGGCGTGACCCCGCTGACCCCGGAACAGTTTCGCTATAAC 60
Qy 64 AACGAAGACGTTATTCACGCGCCGTACCTGGCGCACCAAGGTTGGTATGATATCACCAAG 123
|||||||| || ||||| |||||||| |||||||| || || ||||||||||| |||||
Db 61 AACGAAGATGTGATTCATGCGCCGTATCTGGCGCATCAGGGCTGGTATGATATTACCAAA 120
Qy 124 GCGTTCGACGGCAAAGATAACCTGCTGTGCGGTGCGGCGACCGCGGGTAACATGCTGCAC 183
||||| || ||||||||||||||||||||||| |||||||||||||| |||||||||||
Db 121 GCGTTTGATGGCAAAGATAACCTGCTGTGCGGCGCGGCGACCGCGGGCAACATGCTGCAT 180
Qy 184 TGGTGGTTTGACCAGAACAAGACCGAGATTGAAGCGTACCTGAGCAAACACCCGGATAAG 243
||||||||||| |||||||| ||||| ||||||||||| ||||||||||| ||||| ||
Db 181 TGGTGGTTTGATCAGAACAAAACCGAAATTGAAGCGTATCTGAGCAAACATCCGGAAAAA 240
Qy 244 CAGAAGATCATCTTCAACAACCAAGAACTGTTCGACCTGAAGGCGGCGATCGACACCAAA 303
||||| || || || |||||||| |||||||| || ||||| |||||||| || ||||||
Db 241 CAGAAAATTATTTTTAACAACCAGGAACTGTTTGATCTGAAAGCGGCGATTGATACCAAA 300
Qy 304 GATAGCCAGACCAACAGCCAACTGTTCAACTATTTTCGTGATAAGGCGTTTCCGAACCTG 363
|||||||||||||||||||| ||||| ||||||||||| ||||| |||||||||||||||
Db 301 GATAGCCAGACCAACAGCCAGCTGTTTAACTATTTTCGCGATAAAGCGTTTCCGAACCTG 360
Qy 364 AGCGCGCGTCAGCTGGGTGTGATGCCGGACCTGGTTCTGGATATGTTCATTAACGGCTAC 423
|||||||| |||||||| ||||||||||| ||||| ||||||||||| |||||||||||
Db 361 AGCGCGCGCCAGCTGGGCGTGATGCCGGATCTGGTGCTGGATATGTTTATTAACGGCTAT 420
Qy 424 TATCTGAACGTGTTTAAAACCCAGAGCACCGATGTTAACCGTCCGTACCAAGACAAGGAT 483
||||||||||||||||||||||||||||||||||| ||||| ||||| || || || |||
Db 421 TATCTGAACGTGTTTAAAACCCAGAGCACCGATGTGAACCGCCCGTATCAGGATAAAGAT 480
Qy 484 AAACGTGGTGGCATCTTCGACGCGGTGTTTACCCGTGGTGATCAGACCACCCTGCTGACC 543
||||| || ||||| || || |||||||||||||| || |||||||||||||||||||||
Db 481 AAACGCGGCGGCATTTTTGATGCGGTGTTTACCCGCGGCGATCAGACCACCCTGCTGACC 540
Qy 544 GCGCGTCACGACCTGAAGAACAAAGGTCTGAACGATATTAGCACCATCATTAAGCAAGAA 603
||||| || || ||||| |||||||| |||||||||||||||||||| ||||| || |||
Db 541 GCGCGCCATGATCTGAAAAACAAAGGCCTGAACGATATTAGCACCATTATTAAACAGGAA 600
Qy 604 CTGACCGAAGGTCGTGCGCTGGCGCTGAGCCACACCTATGCGAACGTGAGCATCAGCCAC 663
||||||||||| || ||||||||||||||||| |||||||||||||||||||| |||||
Db 601 CTGACCGAAGGCCGCGCGCTGGCGCTGAGCCATACCTATGCGAACGTGAGCATTAGCCAT 660
Qy 664 GTTATTAACCTGTGGGGTGCGGACTTCAACGCGGAGGGCAACCTGGAAGCGATCTACGTG 723
|| |||||||||||||| ||||| || |||||||| ||||||||||||||||| || |||
Db 661 GTGATTAACCTGTGGGGCGCGGATTTTAACGCGGAAGGCAACCTGGAAGCGATTTATGTG 720
Qy 724 ACCGACAGCGATGCGAACGCGAGCATTGGCATGAAGAAATATTTTGTGGGTATCAACGCG 783
||||| ||||||||||||||||||||||||||||| |||||||||||||| || ||||||
Db 721 ACCGATAGCGATGCGAACGCGAGCATTGGCATGAAAAAATATTTTGTGGGCATTAACGCG 780
Qy 784 CACGGCCACGTTGCGATCAGCGCGAAGAAAATTGAGGGTGAAAACATCGGCGCGCAGGTT 843
|| |||| || ||||| |||||||| |||||||| || |||||||| |||||||||||
Db 781 CATCGCCATGTGGCGATTAGCGCGAAAAAAATTGAAGGCGAAAACATTGGCGCGCAGGTG 840
Qy 844 CTGGGTCTGTTCACCCTGAGCAGCGGCAAGGATATTTGGCAAAAACTGAGC 894
||||| ||||| ||||||||||||||||| ||||||||||| |||||||||
Db 841 CTGGGCCTGTTTACCCTGAGCAGCGGCAAAGATATTTGGCAGAAACTGAGC 891