DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I (claims 1-6, 8-15, and 17) and the species “167L, 171R, 174L, 175E and 177K” amino acid residues being numbered according to SEQ ID NO: 1 in the reply filed on 6/3/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1-6 and 8-21 are pending.
Claims 16 and 18-21 are withdrawn for being drawn to non-elected inventions of Groups II-IV.
Claims 1-6, 8-15 and 17 are under consideration to the extent they read on the elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 1/4/2024 (2) have been considered.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed EP 22306120.1 on 7/27/2022. It is noted, however, that applicant has not filed a certified copy of the EP 22306120.1 application as required by 37 CFR 1.55.
Claim Objections
Claims 10 and 12-13 are objected to because of the following informalities: claims 10 and 13 are objected for the use of abbreviated phrase (AbM, FR, or CDR), which should be described for the first time followed by an abbreviated form placed in a bracket.
Claim 12 is objected to because it is not clear why the term (human) is used within a parenthesis before the term “serum albumin”.
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, 8-10, 12, 14-15 and 17 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.
The written description in this case only sets forth a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) comprising amino acid sequence of SEQ ID NO: 14 or SEQ ID NO: 15, or having CDR1-3 comprising amino acid sequence of SEQ ID NO: 16-18, or 19-21, respectively (recited in claim 13), and therefore the written description is not commensurate in scope with “any polypeptide comprising at least one ISVD that specifically binds to an epitope of FcRn 167L, or 1A or a combination of 167L, 171R, 174L, 175E and 177K, wherein in amino acid number is according to SEQ ID NO: 1”.
The claims broadly encompass any peptide or polypeptide that specifically binds to FcRn to an epitope that may be amino acid residues 1A, 2E, 3S, 4H, 5L, 32P, 97E, 98L, 99G, 100P,101D, 102N, 103T, 164R, 167L, 168E, 171R, 174L, 175E, 177K, 204Y, 205P, 206P, 207E, 208L, 209Q, 255Q, 256H, 257A, 259L, 260A, 261Q, and/or 262P, wherein amino acid residues are numbered according to SEQ ID NO: 1. The claims do not require that a polypeptide or peptide possess any particular feature or structure that may specifically bind to an epitope selected from acid residues 1A, 2E, 3S, 4H, 5L, 32P, 97E, 98L, 99G, 100P,101D, 102N, 103T, 164R, 167L, 168E, 171R, 174L, 175E, 177K, 204Y, 205P, 206P, 207E, 208L, 209Q, 255Q, 256H, 257A, 259L, 260A, 261Q, and/or 262P or a combination e.g., 167L, 171R, 174L, 175E and 177K.
Kim et al. (IDS, WO 2015/167293) an antibody as polypeptide that binds to FcRn for treating autoimmune diseases (see the Title, abstract). They disclose 4 antibodies HL161A, HL161B, HL161C and HL161D (see page 26, [171]). Andersen et al. (IDS, Scientific Reports, 2013, 1-7) teach that FcRn is a key player in binding IgG and albumin ligands, and transport of the ligands to different cellular compartments. They teach a phage display selected nanobodies that target human FcRn. These nanobodies are obtained from a variable domain repertoire library isolated from a Llama immunized with recombinant FcRn. They teach that on candidate Nb218-H4 binds FcRn with high affinity at both acidic and neutral pH, without competing ligand binding and interfering with FcRn function, such as transcytosis of IgG (abstract). Qiu et al. (IDS, J. controlled release 229, 37-47, 2016) teach single chain antibody fragments with pH dependent binding to FcRn enabled prolonged circulation of therapeutic peptide in vivo. They identified a single chain antibody fragment by screening of a phage library and found that FnAb-8 and FnAb-12 can bind a human FcRn with higher affinities than IgG at acidic pH but similar or lower affinity than IgG at pH 7.4.
The specification at pg. 115-118 (Example 1) discloses screening phage display synthetic library to identify FcRn binding polypeptides at pH5.5 and 7.4 (Table 1). The specification uses surface plasmon resonance to determine affinity for FcRn at pH 6.0 and 7.4 (Table 7). The specification at pg. 143 discloses nanobody-VHH (ISVD)-Fc fusion constructs (TP003, 048, 049 and TP050) with half-life at pH 7.4 (Table 20, page 146). The specification does not disclose antibodies that specifically binds to FcRn epitope 167L, 171R, 174L, 175E and 177K of SEQ ID NO: 1. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that 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. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.
As discussed above, the skilled artisan cannot envision the detailed genus of “any polypeptide comprising at least one ISVD that specifically binds to an epitope of FcRn 167L, or 1A or a combination of 167L, 171R, 174L, 175E and 177K, wherein in amino acid number is according to SEQ ID NO: 1” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, only the polypeptide comprising at least one immunoglobulin single variable domain (ISVD) comprising amino acid sequence of SEQ ID NO: 14 or SEQ ID NO: 15, or having CDR1-3 comprising amino acid sequence of SEQ ID NO: 16-18, or 19-21, respectively, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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 no obviousness.
Claim(s) 1-6, 8-10, 12-13, 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. Andersen (IDS, Scientific Reports, 2013, 1-7) in view of Kim et al. (IDS, WO 2015/167293) and Beirnaert et al. (US Pat. No. 8,188,223).
The instantly claimed invention is broadly drawn to a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) specifically binding to an epitope on FcRn, characterized in that the epitope comprises at least one of the following amino acid residues 1A, 2E, 3S, 4H, 5L, 32P, 97E, 98L, 99G, 100P,101D, 102N, 103T, 164R, 167L, 168E, 171R, 174L, 175E, 177K, 204Y, 205P, 206P, 207E, 208L, 209Q, 255Q, 256H, 257A, 259L, 260A, 261Q, and/or 262P, amino acid residues being numbered according to SEQ ID NO: 1 (claims 1-6), wherein the said polypeptide binds to said epitope on FcRn in a pH-dependent manner, such that the binding affinity at a pH between 5.0 and 6.8 is at least three times higher than the binding affinity at a pH of 7.4 (claim 8), wherein said at least one ISVD specifically binding to said epitope on FcRn consists of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively) and is characterized in that: a) CDR1 (according to AbM) has the amino acid sequence of SEQ ID NO: 11 [=G F T F S S Y A M Y] and/or has an amino acid sequence having 4, 3, 2 or only 1 "amino acid difference(s)" (as defined herein) with the sequence of SEQ ID NO: 11; and b) CDR2 (according to AbM) has the amino acid sequence of SEQ ID NO: 12 [= A I S S G G G S T D] and/or has an amino acid sequence having 4, 3, 2 or only 1 "amino acid difference(s)" (as defined herein) with the sequence of SEQ ID NO: 12; and c) CDR3 (according to AbM) has the amino acid sequence of SEQ ID NO: 13 [= D T L Y T S L T S Y S Y], and/or has an amino acid sequence having 4, 3, 2 or only 1 "amino acid difference(s)" (as defined herein) with the sequence of SEQ ID NO: 13 (claim 10), characterized in that said polypeptide further comprises at least one ISVD specifically binding to (human) serum albumin (claim 12), wherein said at least one ISVD specifically binding to serum albumin consists of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively), and is characterized in that: CDR1 is SFGMS (SEQ ID NO: 16), CDR2 is SISGSGSDTLYADSVKG (SEQ ID NO:
17) and CDR3 is GGSLSR (SEQ ID NO: 18), CDR determined according to Kabat definition; and/or in which CDR1 is GFTFRSFGMS (SEQ ID NO: 19), CDR2 is SISGSGSDTL (SEQ ID NO: 20) and CDR3 is GGSLSR (SEQ ID NO: 21), CDR determined according to AbM definition (claim 13), and a pharmaceutical composition comprising a polypeptide of claim 1 (claim 17).
Andersen et al. tach that FcRn is a key player in binding IgG and albumin ligands, and transport of the ligands to different cellular compartments. They teach a phage display selected nanobodies that target human FcRn. These nanobodies are obtained from a variable domain repertoire library isolated from a Llama immunized with recombinant FcRn. They teach that on candidate Nb218-H4 binds FcRn with high affinity at both acidic and neutral pH, without competing ligand binding and interfering with FcRn function, such as transcytosis of IgG (abstract. Figure 1).
Kim et al. (IDS, WO 2015/167293) an antibody as polypeptide that binds to FcRn for treating autoimmune diseases (see the Title, abstract). They disclose 4 antibodies HL161A, HL161B, HL161C and HL161D (see page 26, [171]). They teach that these antibodies bind FcRn with a high affinity in a pH independent manner (page 9, [72]). They teach that the antibodies (Nb) that they isolated are not affected by pH and did not affect FcRn-mediated transcellular transport of IgG (pg. 2, right col.). Regarding claim 15, they teach that Nbs could also directly be conjugated to an enzyme or fluorochromes without losing FcRn biding activity and therefore, the Nbs selected are attractive tools for studying FcRn biology (pg. 2, rt col., pg. 4, left col.). Neither Andersen et al. nor Kim et al teach that the polypeptide that binds to FcRn comprises CDR1-3 having amino acid sequence of SEQ ID NO: CDR1 is SFGMS (SEQ ID NO: 16), CDR2 is SISGSGSDTLYADSVKG (SEQ ID NO: 17) and CDR3 is GGSLSR (SEQ ID NO: 18).
Beirnaert et al teach nanobodies that bind to albumin comprising of 4 framework regions (FR1-4) and 3 complementarity determining regions (CDR1-3) (see col. 5, lines 5+). They teach that CDR1 comprises amino acids SFGMS, CDR2 comprises amino acid sequence SISGSGSDTLYADSVKG, and CDR3 comprises amino acid sequence GGSLR, respectively which are 100% identical to the instantly claimed CDR1-3 of 16, 17, and 18, respectively (see Table I, col. 5).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use albumin binding antibody that comprises CDR1-3 having 100% sequence identity to the instantly claimed polypeptide having CDR1-3 of SEQ ID Nos 16, 17, and 18 as taught by Beirnaert et al for binding to FcRn which has albumin binding domain and FcRn IgG binding domain as taught by Andersen et al and Kim et al. Additionally, one would have been motivated to do so because Beirnaert et al teach that the antibody polypeptide comprising CDR1 comprising amino acids SFGMS, CDR2 comprising amino acid sequence SISGSGSDTLYADSVKG, and CDR3 comprising amino acid sequence GGSLR bind to albumin which is also a ligand for FcRn. Further, one would have a reasonable expectation of success in using antibody comprising CDR1 comprising amino acids SFGMS, CDR2 comprising amino acid sequence SISGSGSDTLYADSVKG, and CDR3 comprising amino acid sequence GGSLR as taught by Beirnaert et al which binds albumin would bind to FcRn because albumin is a ligand for FcRn as taught by Andersen et al. as well as Kim et al. Therefore, the instantly claimed invention would have been obvious to one skill in the art over the combined teachings of the prior art.
Claim(s) 1 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Andersen (IDS, Scientific Reports, 2013, 1-7) in view of Kim et al. (IDS, WO 2015/167293) and Hassanzadeh et al. (US Pub. No. 20200255504).
The instantly claimed invention is broadly drawn to a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) specifically binding to an epitope on FcRn, characterized in that the epitope comprises at least one of the following amino acid residues 1A, 2E, 3S, 4H, 5L, 32P, 97E, 98L, 99G, 100P,101D, 102N, 103T, 164R, 167L, 168E, 171R, 174L, 175E, 177K, 204Y, 205P, 206P, 207E, 208L, 209Q, 255Q, 256H, 257A, 259L, 260A, 261Q, and/or 262P, amino acid residues being numbered according to SEQ ID NO: 1, wherein the polypeptide is attached to an immunoglobulin Fc (claim 15).
The teachings of Andersen et al. and Kim et al. are set forth above. Neither Andersen et al. nor Kim et al teach attaching a immunoglobulin single variable domain with an “Fc”
Hassanzadeh et al. teach that half-life extension of biotherapeutics is dominated by strategies utilizing albumin binding or fusion, fusion to an immunoglobulin Fc region (see paragraph [0090]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use an “ immunoglobulin Fc” as taught by Hassanzadeh et al. to conjugate with a polypeptide which has albumin binding domain and FcRn IgG binding domain as taught by Andersen et al and Kim et al. Additionally, one would have been motivated to do so because Hassanzadeh et al teach that the conjugation of and “immunoglobulin Fc” increases the half-life of a conjugated biotherapeutics. Further, one would have a reasonable expectation of success in using an immunoglobulin Fc to conjugate with the polypeptide taught by Andersen et al. and Kim et al. because Hassanzadeh et al teach that conjugation or fusion of an “Fc” increases the half-life of conjugated or fused biotherapeutics. Therefore, the instantly claimed invention would have been obvious to one skill in the art over the combined teachings of the prior art.
Conclusion
Claims 1-6, 8-10, 12-15 and 17 are rejected.
Claim 11 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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