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 election without traverse of Group I, claims 1, 6, 92-94, 99, and 102-105 in the reply filed on March 5, 2026 is acknowledged.
Claims 50, 51, 53, 55, 58, 59, 66, 67, 75, 76, 82, 83, 85, and 87-91 have been canceled.
Claims 1, 6, 92-94, 99, and 102-105 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of International Patent Application No. PCT/US2022/016229 filed February 11, 2022, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/148,543 filed February 11, 2021. The priority date has been established as February 11, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/22/2025 and 03/05/2026 have been considered and entered by examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: at line 1, "GAG species" should be "glycosaminoglycan (GAG) species". Appropriate correction is required.
Claim 92 is objected to because of the following informalities: "mannose-6-phospate" should be "mannose-6-phosphate". Appropriate correction is required.
Claim 93 is objected to because of the following informalities: at line 2, "in the CSF" should be "in the cerebrospinal fluid (CSF)". Appropriate correction is required.
Claim 99 is objected to because of the following informalities: "mannose-6-phospate" should be "mannose-6-phosphate". Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 92-94, 99, and 102-105 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claims 1 and 6 are drawn to a method of reducing levels of one or more GAG species or treating Hunter syndrome in a subject in need thereof comprising administering to the subject a fusion protein at a dose of about 1 mg/kg, 3 mg/kg or 10 mg/kg, wherein the fusion protein comprises:(a) an iduronate 2-sulfatase (IDS) amino acid sequence, an IDS variant amino acid sequence, or a catalytically active fragment thereof, and(b) an anti-human transferrin receptor antibody, wherein the antibody comprises: i) a heavy chain complementarity determining region 1 (CDR-H1) comprising GYSFTNY (SEQ ID NO: 13), or a sequence having 1 or 2 substitutions relative to SEQ ID NO: 13; ii) a heavy chain CDR-H2 comprising YPGGDY (SEQ ID NO:15), or a sequence having 1 or 2 substitutions relative to SEQ ID NO: 15; iii) a heavy chain CDR-H3 comprising SGNYDEVAY (SEQ ID NO: 16), or a sequence having 1 or 2 substitutions relative to SEQ ID NO: 16; iv) a light chain CDR-L1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO:7), or a sequence having 1 or 2 substitutions relative to SEQ ID NO:7; v) a light chain CDR-L2 comprising KVSNRFS (SEQ ID NO:8), or a sequence having 1 or 2 substitutions relative to SEQ ID NO:8; and vi) a light chain CDR-L3 comprising SQSTHVPWT (SEQ ID NO:9), or a sequence having 1 or 2 substitutions relative to SEQ ID NO:9. Given Broadest Reasonable Interpretation (BRI), the claim encompass fusion proteins with a broad range anti-human transferrin receptor antibodies with large number of different CDR combinations. The specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. (See Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, especially page 1106 3rd column). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP 2163 II.A.3a.ii.
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
In the instant case, the claim encompasses a broad genus of anti-human transferrin receptor antibodies with different CDR combinations. The specification only discloses one specific fusion protein comprising one specific antibody with CDRH1-H3 of SEQ ID NOs:13, 15, and 16, respectively; and CDRL1-L3 of SEQ ID NOs: 7, 8, and 9 (Examples 1-4). By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13: 1619-33 (see Section 3) "Antibody Structure and the Antigen Binding Site" and Figure I). Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). However, antibody variants encompassed by the claims would have been generally expected to be highly structurally diverse, particularly in the CDR sequences. Thus, applicants have not disclosed species sufficient to describe the claimed genus of antibodies to human transferrin receptor with claimed properties.
Claims 92, 93, 99, and 102-105 also encompass a broad genus of anti-human transferrin receptor antibodies with different CDR combinations the same as claims 1 and 6. Taken together, the instant specification has not provided a sufficient description for claims 1, 6, 92-94, 99, and 102-105.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 6 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Sonoda (Sonoda et al., US 2018/0171012 A1, Publication Date: 06/21/2018, cited by IDS of 10/22/2025).
Sonoda teaches that blood-brain barrier (BBB) not only restricts exchange of substances between the blood and the brain but also between the tissue fluid of the central nervous system ([0003]).
Sonoda teaches that anti-human transferrin receptor antibody could be used in the technique to make pharmaceutical agents pass through the BBB ([0011]).
Sonoda teaches an anti-human transferrin receptor antibody (anti-hTfR antibody 3) comprising the light chain variable region of SEQ ID NO: 191 and the heavy chain variable region of SEQ ID NO: 205 ([0139], [0690] and [0691]). As shown below, SEQ ID NO: 205 of Sonoda comprises SEQ ID NOs: 13-15-16 of the instant claims; and SEQ ID NO: 191 of Sonoda comprises SEQ ID NOs: 7-8-9 of the instant claims:
US-15-739-200-205
Query Match 79.8%; Score 103; Length 118;
Best Local Similarity 26.8%;
Matches 22; Conservative 0; Mismatches 0; Indels 60; Gaps 2;
Qy 1 GYSFTNY-------------------YPGGDY---------------------------- 13
||||||| ||||||
Db 26 GYSFTNYWLGWVRQMPGKGLEWMGDIYPGGDYPTYSEKFKVQVTISADKSISTAYLQWSS 85
Qy 14 -------------SGNYDEVAY 22
|||||||||
Db 86 LKASDTAMYYCARSGNYDEVAY 107
US-15-739-200-191
Query Match 85.6%; Score 146.3; Length 112;
Best Local Similarity 40.5%;
Matches 32; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RSSQSLVHSNGNTYLH---------------KVSNRFS---------------------- 23
|||||||||||||||| |||||||
Db 24 RSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRV 83
Qy 24 ----------SQSTHVPWT 32
|||||||||
Db 84 EAEDVGVYYCSQSTHVPWT 102
Sonoda teaches hI2S-humanized anti-hTfR antibody fusion proteins and method of making them (Examples 16 and 17), in particular hI2S fused with anti-hTfR antibody 3, which would read on the fusion protein of the instant claims 1 and 6.
Sonoda teaches the method of using the fusing protein for the treatment of a disease condition of the central nervous system accompanying Hunter syndrome ([0210], [0211], [0311]). In particular, as the anti-hTfR antibody of the present invention can, as a conjugate with human iduronate 2-sulfatase (hI2S), enable hl2S to pass through the blood brain barrier and function in the brain, the antibody can be used for the production of a pharmaceutical agent for parenteral administration for the treatment of a disease condition of the central nervous system accompanying Hunter syndrome ([0621].
Sonoda teaches that the concentration of I2S-anti-hTfR antibody 3 and rhI2S in the brain tissues one hour after administration was 0.368±0.019 μg/g wet weight and 0.00134±0.00232 μg/g wet weight, respectively. The concentration of I2S-anti-TfR antibody 3 reached about 270 times that of rhI2S. This result indicates that rhI2S which scarcely pass through the blood-brain barrier, in general, and does not transfer to the brain, can be made to pass through the blood-brain barrier and transfer into the brain tissues, by combining it with the anti-hTfR antibody. ([0757] and Example 18).
Sonoda teaches administration of a dosage of 1.0 mg/kg of I2S-anti-hTfR antibody 3 to the mice Hunter syndrome model at a frequency of once a week (Example 22, [0767]).
Sonoda teaches that glycosaminoglycans (GAG) species was known to accumulate in the organs of Hunter syndrome patients, who genetically lacked hI2S activity ([0767]). Fig. 10 of Sonoda shows that in all the brain, liver, lung and heart, the concentration of GAG significantly decreased by I2S-anti-hTfR antibody 3 administration ([0768]-[0772]).
Sonoda teaches that the above results in the liver, lung and heart demonstrate that the I2S-anti-hTfR antibody decomposes accumulated GAG not only in the brain but also in other organs. This indicates that the I2S-anti-hTfR antibody (especially I2S-anti-hTfR antibody 3), when administered to patients with Hunter syndrome as a pharmaceutical agent in enzyme replacement therapy, could supplement all the patients' organs including the brain with the enzyme. Also indicated is that the I2S-anti-hTfR antibody can supplement the all the patients' organs including the brain with the enzyme through its intravenous administration ([0773]).
Taken together, Sonoda teaches the methods of instant claims 1 and 6.
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.
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 92-94, 99, and 102-105 are rejected under 35 U.S.C. 103 as being unpatentable over Sonoda (Sonoda et al., US 2018/0171012 A1, Publication Date: 06/21/2018, cited by IDS of 10/22/2025) as applied to claims 1 and 6 above, and further in view of Chelikani (Chelikani et al., WO 2020/132452 A1, Publication Date: 06/25/2020, cited in IDS of 10/22/2025).
Sonoda teaches a method of reducing levels of one or more GAG species or treating Hunter syndrome in a subject in need thereof, comprising the claimed fusion protein as set forth above. However, Sonoda does not teaches “wherein the fusion protein comprises at least about 6 mol/mol sialic acid:fusion protein and/or comprises from about 1.5 to about 2.5 mol/mol mannose-6-phosphate (M6P):fusion protein. This deficiency is remedied by Chelikani.
Chelikani teaches that Hunter syndrome is an X-chromosome-linked recessive lysosomal storage disorder that results from a deficiency in the enzyme iduronate-2-sulfatase ([0003]).
Chelikani teaches a fusion protein comprising an immunoglobulin and an iduronated-2-sulfatase (I2S, recited as IDS in the instant application) ([0006], and claim 1).
Chelikani teaches a suitable fusion protein further includes a lysosomal targeting moiety through a M6P residue ([0084]).
Chelikani teaches the purified protein comprise about 3.0 mol/mol mannose-6 phosphate residue per molecule ([0084] and claim 4). Base on the specification (see page 32, lines 23-26): “the term “about” when used to modify an amount specified in a numeric value or range indicate that the numeric value as well as reasonable deviation from the value known to the skilled person in the art, for example ± 20%, ±10%, or ± 5%, are within the intended meaning of the recited value”. Thus, about 3.0 mol/mol would overlap with about 1.5 to about 2.5 mol/mol recited by the instant claims 92 and 99.
Chelikani teaches that sialic acid residues on proteins may prevent, reduce or inhibit their rapid in vivo clearance via asialoglycoprotein receptors that are present on hepatocytes. Thus, it is thought that I2S fusion proteins that have relatively high sialic acid content typically have a relatively long circulation time in vivo ([0139]).
Chelikani teaches that the sialic acid content of a purified I2S fusion protein may be at least 15 mol/mol ([0141]). This overlap the ranges of instant claims 92 and 99.
Chelikani teaches making fusion proteins comprising various levels of M6P and sialic acids (Example 1 and Table 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Sonoda and Chelikani and to modify the method by using an I2S-anti- anti-hTfR fusion protein with at least about 6 mol/mol sialic acid:fusion protein and/or comprises from about 1.5 to about 2.5 mol/mol mannose-6-phosphate (M6P):fusion protein. Based on the teachings of Chelikani, one of ordinary skilled in the art would have had a reasonable expectation that the modified fusion protein would have better therapeutic properties for treating Hunter syndrome and/or reducing GAG species, because M6P can help to direct the fusion protein to lysosome and sialic acid can prevent, reduce or inhibit their rapid in vivo clearance. Since the method of making the fusion protein are well known in the art, as evidenced by Chelikani, one of ordinary skilled in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to generate a better therapeutic agent for Hunter syndrome.
Regarding claim 93, the reduced levels recited are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the reduced level of one or more GAG species in the CSF are given no weight. A decrease of GAG species is expected compared to controls and so the claim is obvious.
Regarding claim 94, Chelikani teaches that I2S cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans: dermatan sulfate and heparan sulfate ([0003]). It would have prima facie been obvious to the fusion protein taught by Sonoda and Chelikani would be able to reduce the level of dermatan sulfate and heparan sulfate.
Regarding claims 102-105, Sonoda teaches administration of a dosage of 1.0 mg/kg of I2S-anti-hTfR antibody 3 to the mice Hunter syndrome model at a frequency of once a week (Example 22, [0767]). In addition, it is noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
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.
Application No. 19/304, 112
Claims 1, 6, 92-94, 99, and 102-105 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 102-120 of copending Application No. 19/304, 112 (hereinafter Appl. 112) in view of Sonoda (Sonoda et al., US 2018/0171012 A1, Publication Date: 06/21/2018, cited by IDS of 10/22/2025) and Chelikani (Chelikani et al., WO 2020/132452 A1, Publication Date: 06/25/2020, cited in IDS of 10/22/2025). It is noted that this application has been allowed recently.
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 112 teaches a pharmaceutical composition comprising a fusion protein and a pharmaceutically acceptable excipient, wherein the fusion protein comprises: (a) two light chain amino acid sequences, each consisting of SEQ ID NO: 5; (b) a first heavy chain amino acid sequence, a linker, and an IDS amino acid sequence, which together consist of SEQ ID NO:17 or SEQ ID NO: 18; and (c) a second heavy chain amino acid sequence, a linker, and an IDS amino acid sequence, which together consist of SEQ ID NO: 17 or SEQ ID NO:18;and wherein the fusion protein comprises at least about 6 mol/mol sialic acid:fusion protein (claim 102).
As shown below, SEQ ID NO: 5 comprises SEQ ID NOs: 7-8-9 of the instant application (underlined):
>US-19-304-112-5 ANTI-TRANSFERRIN RECEPTOR FUSION PROTEINS AND METHODS OF USE THEREOF
DIVMTQTPLSLSVTPGQPASISCRSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHVPWTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
As shown below, SEQ ID NO: 17 comprises SEQ ID NOs: 13-15-16 of the instant application (underlined):
>US-19-304-112-17 ANTI-TRANSFERRIN RECEPTOR FUSION PROTEINS AND METHODS OF USE THEREOF
EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWLGWVRQMPGKGLEWMGDIYPGGDYPTY
SEKFKVQVTISADKSISTAYLQWSSLKASDTAMYYCARSGNYDEVAYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGKGSSETQANSTTDALNVLLIIVDDLRPSLGCYG
DKLVRSPNIDQLASHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRLYDFNSYWRVHAGN
FSTIPQYFKENGYVTMSVGKVFHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKTCRGPD
GELHANLLCPVDVLDVPEGTLPDKQSTEQAIQLLEKMKTSASPFFLAVGYHKPHIPFRYP
KEFQKLYPLENITLAPDPEVPDGLPPVAYNPWMDIRQREDVQALNISVPYGPIPVDFQRK
IRQSYFASVSYLDTQVGRLLSALDDLQLANSTIIAFTSDHGWALGEHGEWAKYSNFDVAT
HVPLIFYVPGRTASLPEAGEKLFPYLDPFDSASQLMEPGRQSMDLVELVSLFPTLAGLAG
LQVPPRCPVPSFHVELCREGKNLLKHFRFRDLEEDPYLPGNPRELIAYSQYPRPSDIPQW
NSDKPSLKDIKIMGYSIRTIDYRYTVWVGFNPDEFLANFSDIHAGELYFVDSDPLQDHNM
YNDSQGGDLFQLLMP
Thus, the fusion protein of Appl. 112 reads the fusion protein of the instant claims.
The claims of Appl. 112 teaches wherein the fusion protein comprises from about 6 to about 19 mol/mol sialic acid:fusion protein (claim 103); wherein the fusion protein comprises from about 1.5 to about 2.5 mol/mol mannose-6-phospate (M6P):fusion protein (claim 107).
Although the claims of Appl. 112 teach the fusion proteins of the instant claims, the claims of Appl. 112 do not teach the methods as instantly claimed.
Sonoda and Chelikani’s teachings are described above. In particular, Sonoda teaching the fusion protein with identical antibody variable regions can be used for reducing GAG species and for treating Hunter syndrome. Chelikani teaches that M6P can direct the fusion protein to lysosome and sialic acid can delay in vivo clearance of the fusion protein.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 112, Sonoda and Chelikani and to use the I2S-anti- anti-hTfR fusion protein with at least about 6 mol/mol sialic acid:fusion protein and/or comprises from about 1.5 to about 2.5 mol/mol mannose-6-phosphate (M6P):fusion protein taught by the claims of Appl. 112 for reducing GAG species and for treating Hunter syndrome. Based on the teachings of Sonoda and Chelikani, one of ordinary skilled in the art would have had a reasonable expectation that the fusion protein would have therapeutic properties for treating Hunter syndrome and/or reducing GAG species, because Sonoda teaches I2S-anti- anti-hTfR fusion protein can be used for reducing GAG species and treating Hunter syndrome; Chelikani teaches that the M6P can help to direct the fusion protein to lysosome and sialic acid can prevent, reduce or inhibit their rapid in vivo clearance. Since the fusion protein are well known in the art, as evidenced by the claims of Appl. 112, one of ordinary skilled in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to develop an effective method for treating Hunter syndrome and reducing GA species.
Regarding claim 93, the reduced levels recited are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the reduced level of one or more GAG species in the CSF are given no weight. A decrease of GAG species is expected compared to controls and so the claim is obvious.
Regarding claim 94, Chelikani teaches that I2S cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans: dermatan sulfate and heparan sulfate ([0003]). It would have prima facie been obvious to the fusion protein taught by Sonoda and Chelikani would be able to reduce the level of dermatan sulfate and heparan sulfate.
Regarding claims 102-105, Sonoda teaches administration of a dosage of 1.0 mg/kg of I2S-anti-hTfR antibody 3 to the mice Hunter syndrome model at a frequency of once a week (Example 22, [0767]). In addition, it is noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Application No. 19/349,405
Claims 1, 6, 92-94, 99, and 102-105 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-142 of copending Application No. 19/349,405 (hereinafter Appl. 405) in view of Sonoda (Sonoda et al., US 2018/0171012 A1, Publication Date: 06/21/2018, cited by IDS of 10/22/2025) and Chelikani (Chelikani et al., WO 2020/132452 A1, Publication Date: 06/25/2020, cited in IDS of 10/22/2025).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 405 teaches a protein comprising: (a) a first Fc polypeptide that is linked to an enzyme replacement therapy (ERT) enzyme, an ERT enzyme variant, or a catalytically active fragment thereof; and (b) a second Fc polypeptide that forms an Fc dimer with the first Fc polypeptide, wherein the first Fc polypeptide and/or the second Fc polypeptide does not include an immunoglobulin heavy and/or light chain variable region sequence or an antigen- binding portion thereof (claim 1).
The claims of Appl. 405 teaches the protein of claim 1, wherein the ERT enzyme is iduronate 2-sulfatase (IDS), an IDS variant, or a catalytically active fragment thereof (claim 2), wherein the first Fc polypeptide and/or the second Fc polypeptide specifically binds to a transferrin receptor (TfR) (claim 47). It is noted that the scope of the proteins encompassed by claim 1 of Appl. 405 overlaps with the fusion proteins encompassed by instant claims.
Although the claims of Appl. 405 teach the fusion proteins of the instant claims, the claims of Appl. 405 do not teach the methods as instantly claimed.
Sonoda and Chelikani’s teachings are described above. In particular, Sonoda teaching the fusion protein with identical antibody variable regions can be used for reducing GAG species and for treating Hunter syndrome. Chelikani teaches that M6P can direct the fusion protein to lysosome and sialic acid can delay in vivo clearance of the fusion protein. It is noted that the I2S-anti-hTfR antibody 3 of Sonoda comprises hI2S linked to C-terminal of heavy chain of anti-TfR (SEQ ID NO: 210, which comprises a Fc region) and light chain of anti-hTfR antibody 3 ([0749], [0752] of Sonoda). Thus, I2S-anti-hTfR antibody 3 of Sonoda is a species of proteins encompassed by claim1 of Appl. 405.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 405, Sonoda and Chelikani and to use the I2S-anti- anti-hTfR fusion protein with at least about 6 mol/mol sialic acid:fusion protein and/or comprises from about 1.5 to about 2.5 mol/mol mannose-6-phosphate (M6P):fusion protein taught by the claims of Appl. 405 for reducing GAG species and for treating Hunter syndrome. Based on the teachings of Sonoda and Chelikani, one of ordinary skilled in the art would have had a reasonable expectation that the fusion protein would have therapeutic properties for treating Hunter syndrome and/or reducing GAG species, because Sonoda teaches I2S-anti- anti-hTfR fusion protein can be used for reducing GAG species and treating Hunter syndrome; Chelikani teaches that the M6P can help to direct the fusion protein to lysosome and sialic acid can prevent, reduce or inhibit their rapid in vivo clearance. Since the fusion protein are well known in the art, as evidenced by the claims of Appl. 405, one of ordinary skilled in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to develop an effective method for treating Hunter syndrome and reducing GA species.
Regarding claim 93, the reduced levels recited are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the reduced level of one or more GAG species in the CSF are given no weight. A decrease of GAG species is expected compared to controls and so the claim is obvious.
Regarding claim 94, Chelikani teaches that I2S cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans: dermatan sulfate and heparan sulfate ([0003]). It would have prima facie been obvious to the fusion protein taught by Sonoda and Chelikani would be able to reduce the level of dermatan sulfate and heparan sulfate.
Regarding claims 102-105, Sonoda teaches administration of a dosage of 1.0 mg/kg of I2S-anti-hTfR antibody 3 to the mice Hunter syndrome model at a frequency of once a week (Example 22, [0767]). In addition, it is noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642
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