DETAILED ACTION
Notice of Pre-AIA or AIA 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 .
Response to Amendments and Arguments
2. Claims 1-10, 13-15, 18-20, 23, 24, 29 and 79-83 are pending.
Claims 25-28 have been cancelled.
Claims 1-10, 13-15, 18-20, 23, 24 and 29 have been amended.
Claims 79-83 have been added.
Claims 1-10, 13-15, 18-20, 23, 24 and 29 are examined on the merits.
Priority
3. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting,
Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the instant filed application fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Applicant’s instant application, Application No. 18/041,527 (filed February 13, 2023) does not provide support a composition comprising a variant soluble B-cell maturation antigen (sBCMA) comprising at least one amino acid substitution as compared to SEQ ID NO: 1 with amino acid substitution(s) at designated position number(s), wherein said variant sBCMA has at least 80% sequence identify to SEQ ID NO: 1, wherein the said variant sBCMA has:
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127
573
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, see last five (5) lines of claim 1. Accordingly, claims 1-10, 13-15, 18-20 and 23-29 are entitled to the benefit of the instant application filed February 27, 2013.
Withdrawn Objections
Claim Objections
4. The objection of claims 4-10, 13-15, 18-20, 23 and 24 under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim(s) is withdrawn in light of the amendment to the claims, see In the Claims submitted April 23, 2026. Claims 25-28 have been cancelled.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 102
5. The rejection of claim(s) 2 under 35 U.S.C. 102(a)(1) as being anticipated by Kelley et al., US 2007/0249530 A1 (published October 25, 2007) is withdrawn in light of the amendment to the claim, see In the Claims submitted April 23, 2026.
New Claim Objections
Claim Objections
6. Claim 1 is objected to because of the following informality: on line 3 of the claim the term “numberr” is misspelled. It should be deleted and replaced with the proper spelling of the word, number.
Correction is required.
7. Claim 23 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 24. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 1-10, 13-15, 18-20, 23, 24 and 29 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. THIS IS A NEW MATTER REJECTION. 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.
Applicant has amended claim 1 to include new limitations, (i) and (ii) not supported by the Specification, contrary to Applicant’s assertions, see Remarks filed April 23, 2026, page 8, Summary of Amendments; page 9, last paragraph (para.); and herein and particular, the last seven (7) lines of claim 1.
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302
579
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Figure 4, 1st panel on top row recites the equilibrium dissociation constant (Kd) for A Proliferation Inducing Ligand (APRIL) is approximately 25 pM and not plainly 25 pM. Moreover, the disclosure does not seem to support the Kd that is less than 25 or the Kd of less than 30 pM for B-cell Activating Factor of the TNF family (BAFF).
The disclosure also does not seem to support the maximum binding capacity (Bmax) of greater than 7,000 for APRIL and greater than 80 for BAFF.
The designated figures, the pages noted within the Remarks on page 8, as well as the entire Specification has been reviewed and there is no support for the new limitations. Applicant is requested to point out by figure number, page, section and/or any other identifying information where support is cited and/or noted for these new limitations or delete the new matter.
Claim Rejections - 35 USC § 101
10. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
11. The claimed invention (claims 1-10, 13-15, 18-20, 23, 24 and 29) continues and is to be directed to non-statutory subject matter.
Applicant argues “[a]s can be seen in Figures 4 and 5…, the naturally occurring BCMA wild type has a kd of 25 pM and Bmax of 6563 for APRIL and a non-measurable kd and Bmax of 78.3 for BAFF. As amended, claim 1 includes kd and/or Bmax metrics for either or both of APRIL and BAFF which confer affinity for SEQ ID NO: 1. Under Prong 1 of Step 2A of 35 U.S.C. 101, claim 1 does not recite a judicial exception that is a natural product, and the claim is directed to patent eligible subject matter.”, see Remarks submitted April 23, 2026, page 9, last paragraph (para.).
Applicant’s arguments have been carefully considered, however fail to persuade.
As amended claim 1 reads, the variant sBCMA is the same as that claimed. Reviewing the sequence alignments at the close of the instant rejection, the disclosed variant SBCMA shares at least 80% sequence identity to Applicant’s SEQ ID NO: 1 and an amino acid substitution at position number 22. Absent evidence to the contrary, the maximum binding capacity (Bmax) is greater than 7,000 for APRIL and the Bmax is greater than 80 for BAFF, as well as exhibits enhanced binding affinity for APRIL or BAFF as compared to SEQ ID NO: 1. Accordingly, the rejection is maintained.
The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because it reads on a composition of matter and product of nature, a natural product, amino acid sequence, SEQ ID NO: 1. The claimed polypeptide comprising at least one amino acid substitution is a natural product that exists in nature. The polypeptide is identified as a tumor necrosis factor receptor superfamily member 17 or a B-cell maturation protein, see sequence alignments and information therein.
The combination of additional elements such as pharmaceutical preparation, pharmaceutical composition does not add a meaningful limitation as it is merely a nominal or token extra-solution component listed in the claims and is nothing more than an attempt to generally link the product of nature to a particular technology. The naturally occurring polypeptide and additional elements, separate and in combination, do not add significantly. Additional limitations such as the pharmaceutical preparation and pharmaceutical composition provide a means of holding, storing or placing the said polypeptide. These limitations are well-understood, routine, conventional activity in the life science arts and are regarded as claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Hence, there is no inventive concept. See the 2014 Interim Guidance on Patent Subject Matter Eligibility and Federal Register (http://federalregister.gov/a/2014-29414); Federal Register Vol. 81, No. 88, Friday, May 6, 2016 / Proposed Rules; and Federal Register Vol. 84, No. 4, Monday, January 7, 2019; and FDsys.gov.
The claimed composition comprising a variant soluble B-cell maturation antigen (sBCMA) product has not been altered or different in physical structure, wherein the said product is not markedly different from those that occur in nature. Applicant has not set forth descriptions or evidence of this product that rises to the level of a marked difference in structure, function or other characteristic of the naturally occurring counterpart in its naturally occurring counterpart in its natural state. While the polypeptide product is isolated from the protein and the isolation does structurally change the protein, the resultant difference (i.e. the breaking of bonds) is not significant enough to render the peptide markedly different because the protein structure and sequence of the peptide has not been altered. The polypeptide has the same function as its natural counterpart. The claims do not recite additional elements/steps in addition to the judicial exception at a high level of generality. The claimed invention does not recite additional elements/steps with the judicial exception. The claims do not recite additional elements/steps with the judicial exception that are insignificant extra-solution activity and do not recite steps that amount to nothing more than a mere field of use. The claims are directed to a nature-based product which is a naturally occurring protein and does not amount to significantly more than the judicial exception, hence the claims are not patent eligible.
RESULT 11 from 1.rup database.
F7IJE9_CALJA
ID F7IJE9_CALJA Unreviewed; 183 AA.
AC F7IJE9; F7IH37;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 20-JUN-2018, sequence version 2.
DT 18-JUN-2025, entry version 44.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 17 {ECO:0000256|ARBA:ARBA00072357};
DE AltName: Full=B-cell maturation protein {ECO:0000256|ARBA:ARBA00076632};
GN Name=TNFRSF17 {ECO:0000313|Ensembl:ENSCJAP00000029515.3};
OS Callithrix jacchus (White-tufted-ear marmoset).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Callithrix; Callithrix.
OX NCBI_TaxID=9483 {ECO:0000313|Ensembl:ENSCJAP00000029515.3, ECO:0000313|Proteomes:UP000008225};
RN [1] {ECO:0000313|Ensembl:ENSCJAP00000029515.3}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Warren W., Ye L., Minx P., Worley K., Gibbs R., Wilson R.K.;
RL Submitted (MAR-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSCJAP00000029515.3}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (MAR-2025) to UniProtKB.
CC -!- FUNCTION: Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes
CC B-cell survival and plays a role in the regulation of humoral immunity.
CC Activates NF-kappa-B and JNK. {ECO:0000256|ARBA:ARBA00054809}.
CC -!- SUBUNIT: Associates with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.
CC {ECO:0000256|ARBA:ARBA00065494}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004183}; Single-
CC pass type III membrane protein {ECO:0000256|ARBA:ARBA00004183}.
DR RefSeq; XP_002755963.1; XM_002755917.6.
DR AlphaFoldDB; F7IJE9; -.
DR FunCoup; F7IJE9; 635.
DR GeneID; 100397314; -.
DR KEGG; cjc:100397314; -.
DR CTD; 608; -.
DR GeneTree; ENSGT00940000154485; -.
DR InParanoid; F7IJE9; -.
DR OMA; CHLRCSN; -.
DR OrthoDB; 9894478at2759; -.
DR TreeFam; TF340640; -.
DR Proteomes; UP000008225; Chromosome 12.
DR Bgee; ENSCJAG00000016037; Expressed in liver and 4 other cell types or tissues.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0002260; P:lymphocyte homeostasis; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:InterPro.
DR CDD; cd13414; TNFRSF17; 1.
DR FunFam; 4.10.1290.10:FF:000003; Tumor necrosis factor receptor superfamily member 17; 1.
DR Gene3D; 4.10.1290.10; Tumor necrosis factor receptor superfamily; 1.
DR InterPro; IPR015337; BCMA_Tall-1-bd.
DR InterPro; IPR043521; TNFR_13C/17.
DR InterPro; IPR022320; TNFR_17.
DR PANTHER; PTHR20437; TUMOR NECROSIS FACTOR RECEPTOR SUBFAMILY MEMBER 13/17; 1.
DR PANTHER; PTHR20437:SF0; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 17; 1.
DR Pfam; PF09257; BCMA-Tall_bind; 1.
DR PRINTS; PR01967; TNFACTORR17.
DR SUPFAM; SSF57586; TNF receptor-like; 1.
PE 4: Predicted;
KW Adaptive immunity {ECO:0000256|ARBA:ARBA00023130};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW Immunity {ECO:0000256|ARBA:ARBA00022859};
KW Membrane {ECO:0000256|ARBA:ARBA00023136};
KW Receptor {ECO:0000256|ARBA:ARBA00023170};
KW Reference proteome {ECO:0000313|Proteomes:UP000008225};
KW Signal-anchor {ECO:0000256|ARBA:ARBA00022968};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989}.
FT DOMAIN 8..43
FT /note="BCMA TALL-1 binding"
FT /evidence="ECO:0000259|Pfam:PF09257"
SQ SEQUENCE 183 AA; 20027 MW; C1E18582751B9892 CRC64;
Query Match 86.4%; Score 257.5; Length 183;
Best Local Similarity 92.5%;
Matches 49; Conservative 0; Mismatches 3; Indels 1; Gaps 1;
Qy 1 MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTN 53
||||| ||||||||||||||| |||||| ||||||||||||||| ||||||||
Db 1 MLQMAQQCSQNEYFDSLLHACKPCQLRC-SNTPPLTCQRYCNASGTNSVKGTN 52
RESULT 29 from 1.rup database.
A0A2K6F8M8_PROCO
ID A0A2K6F8M8_PROCO Unreviewed; 183 AA.
AC A0A2K6F8M8;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 18-JUN-2025, entry version 32.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 17 {ECO:0000256|ARBA:ARBA00072357};
DE AltName: Full=B-cell maturation protein {ECO:0000256|ARBA:ARBA00076632};
GN Name=TNFRSF17 {ECO:0000313|Ensembl:ENSPCOP00000010338.1};
OS Propithecus coquereli (Coquerel's sifaka) (Propithecus verreauxi
OS coquereli).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lemuriformes;
OC Indriidae; Propithecus.
OX NCBI_TaxID=379532 {ECO:0000313|Ensembl:ENSPCOP00000010338.1, ECO:0000313|Proteomes:UP000233160};
RN [1] {ECO:0000313|Ensembl:ENSPCOP00000010338.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (MAR-2025) to UniProtKB.
CC -!- FUNCTION: Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes
CC B-cell survival and plays a role in the regulation of humoral immunity.
CC Activates NF-kappa-B and JNK. {ECO:0000256|ARBA:ARBA00054809}.
CC -!- SUBUNIT: Associates with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.
CC {ECO:0000256|ARBA:ARBA00065494}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004183}; Single-
CC pass type III membrane protein {ECO:0000256|ARBA:ARBA00004183}.
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR RefSeq; XP_012503068.1; XM_012647614.1.
DR AlphaFoldDB; A0A2K6F8M8; -.
DR STRING; 379532.ENSPCOP00000010338; -.
DR Ensembl; ENSPCOT00000020916.1; ENSPCOP00000010338.1; ENSPCOG00000016633.1.
DR GeneID; 105813035; -.
DR KEGG; pcoq:105813035; -.
DR CTD; 608; -.
DR GeneTree; ENSGT00940000154485; -.
DR OMA; CHLRCSN; -.
DR OrthoDB; 59623at9443; -.
DR Proteomes; UP000233160; Unassembled WGS sequence.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0002260; P:lymphocyte homeostasis; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:InterPro.
DR CDD; cd13414; TNFRSF17; 1.
DR FunFam; 4.10.1290.10:FF:000003; Tumor necrosis factor receptor superfamily member 17; 1.
DR Gene3D; 4.10.1290.10; Tumor necrosis factor receptor superfamily; 1.
DR InterPro; IPR015337; BCMA_Tall-1-bd.
DR InterPro; IPR043521; TNFR_13C/17.
DR InterPro; IPR022320; TNFR_17.
DR PANTHER; PTHR20437; TUMOR NECROSIS FACTOR RECEPTOR SUBFAMILY MEMBER 13/17; 1.
DR PANTHER; PTHR20437:SF0; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 17; 1.
DR Pfam; PF09257; BCMA-Tall_bind; 1.
DR PRINTS; PR01967; TNFACTORR17.
DR SUPFAM; SSF57586; TNF receptor-like; 1.
PE 4: Predicted;
KW Adaptive immunity {ECO:0000256|ARBA:ARBA00023130};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW Immunity {ECO:0000256|ARBA:ARBA00022859};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW Receptor {ECO:0000256|ARBA:ARBA00023170};
KW Reference proteome {ECO:0000313|Proteomes:UP000233160};
KW Signal-anchor {ECO:0000256|ARBA:ARBA00022968};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|SAM:Phobius}.
FT TRANSMEM 53..76
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 8..44
FT /note="BCMA TALL-1 binding"
FT /evidence="ECO:0000259|Pfam:PF09257"
SQ SEQUENCE 183 AA; 20174 MW; B31C26721F842E20 CRC64;
Query Match 80.4%; Score 239.5; Length 183;
Best Local Similarity 83.3%;
Matches 45; Conservative 2; Mismatches 6; Indels 1; Gaps 1;
Qy 1 MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA 54
| ||| || |||||||||||| || ||| |:|||| |||||||:||||||||||
Db 1 MFQMARQCFQNEYFDSLLHACKPCHLRC-SDTPPLICQRYCNANVTNSVKGTNA 53
ALIGNMENTS with US-10-587-370, Publication No.2007/0249530 A1 (published October 25, 2007)
Database : US-10-587-370-30.pep:*
Search completed: January 7, 2026, 19:27:47
Title: US-18-041-527A-1
Perfect score: 298
Sequence: 1 MLQMAGQCSQNEYFDSLLHA..........LTCQRYCNASVTNSVKGTNA 54
Searched: 1 seqs, 296 residues
Database : US-10-587-370-31.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 257 86.2 296 1 US-10-587-370-31 BCMA POLYPEPTIDES
RESULT 2
US-10-587-370-31
Query Match 86.2%; Score 257; DB 1; Length 296;
Best Local Similarity 97.9%;
Matches 46; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 5 AGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKG 51
||||||||||||||||| |||||||||||||||||||||||||||||
Db 18 AGQCSQNEYFDSLLHACKPCQLRCSSNTPPLTCQRYCNASVTNSVKG 64
Search completed: January 7, 2026, 19:31:14
Claim Rejections - 35 USC § 102
12. 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.
13. The rejection of claim(s) 1, 3, 23, 24 and 29 under 35 U.S.C. 102(a)(1) as being anticipated by Kelley et al., US 2007/0249530 A1 (published October 25, 2007) is maintained and made.
Applicant argues “[a]s amended, claim 1 includes enhanced binding affinities for either or both of APRIL (kd of less than 25 pM or Bmax of greater than 7,000) and BAFF (kd of less than 30 pM or Bmax of greater than 80) which Kelley does not disclose. Kelley is silent on Bmax values, however, Kelley does disclose kd values for two BCMA variants in Table 5 (reproduced below) [on page 11 of the Remarks], see Remarks submitted April 23, 2026, pages 10 and 11.
Applicant’s arguments have been carefully considered, however fail to persuade.
As amended claim 1 reads, the variant sBCMA is the same as that claimed. Reviewing the sequence alignment at the close of the instant rejection, the disclosed variant SBCMA shares at least 80% sequence identity to Applicant’s SEQ ID NO: 1 and an amino acid substitution at position number 22. Absent evidence to the contrary, the maximum binding capacity (Bmax) is greater than 7,000 for APRIL and the Bmax is greater than 80 for BAFF, as well as exhibits enhanced binding affinity for APRIL or BAFF as compared to SEQ ID NO: 1. Accordingly, the rejection is maintained and made.
Kelley discloses “…a polypeptide of this invention is a BCMA variant that has been derived from a mammalian BCMA polypeptide sequence wherein at least one amino acid residue corresponding to a residue selected from the group consisting of …I22…of FIG. 5 has been altered. According to one embodiment, the BCMA variant has at least one substitution corresponding to a mammalian BCMA residue selected from the group consisting of I22K, R27Y, R27A, Q25D, Y13S, Y13F and Y13A.”, see page 2, section 0011; page 4, section 0045; page 5, section 0054; claims 17-21 on pages 52 and 53.
“In one embodiment, the BCMA variant comprises alterations at an amino acid residue corresponding to I22 and an amino acid residue corresponding to any one of the group consisting of F14 and Q25 of FIG. 5. In one preferred embodiment, the BCMA variant is substituted with I22K in combination with any one or all of the group consisting of F14A and Q25A... In another embodiment, the BCMA variant is substituted with Q25D in combination with R27Y or R27A (Q25D/R27 variant). In another embodiment, the Q25D/R27 variant is further substituted with Y13S, Y13F or Y13A.”, see page 2, section 0012; and Example 6 on page 33.
“The present invention further provides a composition comprising a polypeptide or nucleic acid molecule of this invention optionally further comprising a pharmaceutically acceptable carrier.”, see page 3, section 0033; and page 8, section 0073.
The disclosed polypeptide is designed with a Fc region and at least 80% sequence identical to SEQ ID NO: 1, see page 13, section 0125; Example 2 on page 28; Example 6 on page 33; and sequence alignments.
GenCore version 6.5.2
Perfect score: 298
Sequence: 1 MLQMAGQCSQNEYFDSLLHA..........LTCQRYCNASVTNSVKGTNA 54
RESULT 2
US-10-587-370-31, Publication No. US 2007/0249530 A1 (published October 25, 2007)
US-10-587-370-31.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 257 86.2 296 1 US-10-587-370-31 BCMA POLYPEPTIDES
Query Match 86.2%; Score 257; DB 1; Length 296;
Best Local Similarity 97.9%;
Matches 46; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 5 AGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKG 51
||||||||||||||||| |||||||||||||||||||||||||||||
Db 18 AGQCSQNEYFDSLLHACKPCQLRCSSNTPPLTCQRYCNASVTNSVKG 64
Claim Rejections - 35 USC § 103
14. 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.
15. The rejection of claim(s) 1-5, 23, 24 and 29 under 35 U.S.C. 103 as being unpatentable over Result 29, Accession number A0A2K6F8M8, sequence version 1 (28 March 2018), and further in view of Kelley et al., US 2007/0249530 A1 (published October 25, 2007) is maintained and made.
Applicant avers “[a]s amended, claim 1 includes enhanced binding affinities for either or both of APRIL (kd of less than 25 pM or Bmax of greater than 7,000) and BAFF (kd of less than 30 pM or Bmax of greater than 80) which neither Result 29 nor Kelley disclose, teach, or suggest. Result 29 does not disclose any binding affinity data, therefore, Result 29 cannot disclose, teach, or suggest the presently recited enhanced kd and Bmax values for APRIL and/or BAFF. As discussed above, in response to the § 102 rejection, Kelley does not disclose Bmax values and the kd values of Kelley are at least an order of magnitude worse than those recited in amended claim 1. Accordingly, Kelley does not provide one of ordinary skill in the art with any teaching or suggestion that the presently recited enhanced binding affinities are possible or how to achieve them. Kelley fails to disclose, teach, or suggest the nature of the binding affinity or any mode of having to understand how to enhance binding affinities of the disclosed peptides. Further, Kelley fails to disclose, teach, or suggest the quantitative nature of the magnitudes recited in the currently amended claims. One of ordinary skill would not be motivated to alter Result 29 or Kelley to arrive at the mutations disclosed herein, much less the values associated with their physical features.
Applicant’s arguments have been carefully considered, however fail to persuade.
As amended claim 1 reads, the variant sBCMA is the same as that claimed. Reviewing the sequence alignment at the close of the instant rejection, the disclosed variant SBCMA shares at least 80% sequence identity to Applicant’s SEQ ID NO: 1. Absent evidence to the contrary, the maximum binding capacity (Bmax) is greater than 7,000 for APRIL and the Bmax is greater than 80 for BAFF, as well as exhibits enhanced binding affinity for APRIL or BAFF as compared to SEQ ID NO: 1. Accordingly, the rejection is maintained and made.
Accession number A0A2K6F8M8 teaches variant soluble B-cell maturation antigen (sBCMA) comprising at least nine amino acid substitutions as compared to SEQ ID NO: 1, wherein said amino acid substitution is at a position number selected from 2, 6, 9, 22, 29, 31, 36 and 44, in particular S9F, N31D, T36I and S44N, see sequence alignment.
The Result from Accession number A0A2K6F8M8 does not teach the sBCMA variant is comprised within a composition, as well as a sBCMA variant – Fc fusion protein comprised within a composition.
However, Kelley teaches a polypeptide that is a sBCMA variant derived from a mammalian BCMA polypeptide sequence, see page 2, sections 0011 and 0012; page 4, section 0045; page 5, section 0054; claims 17-21 on pages 52 and 53; and Example 6 on page 33. The BCMA variant polypeptide is designed with a Fc region and comprised with a pharmaceutically acceptable carrier, see page 3, section 0033; page 8, section 0073, page 13, section 0125; and Example 6 on page 33.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a Fc domain and package the sBCMA in a pharmaceutical composition because it has been successfully done by Kelley, see the entire document.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings known in the art and Kelley to design a polypeptide with a Fc domain to facilitate the polypeptide’s effector functions and include the fusion protein within a pharmaceutical composition for in vivo treatment of “…diseases characterized by increased levels of expression of BAFF, APRIL and/or BCMA as compared to subjects not suffering from the disease.”, see page 3, section 0035 of Kelley and all documents in their entireties.
RESULT 29 from 1.rup database.
A0A2K6F8M8_PROCO
ID A0A2K6F8M8_PROCO Unreviewed; 183 AA.
AC A0A2K6F8M8;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 18-JUN-2025, entry version 32.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 17 {ECO:0000256|ARBA:ARBA00072357};
DE AltName: Full=B-cell maturation protein {ECO:0000256|ARBA:ARBA00076632};
GN Name=TNFRSF17 {ECO:0000313|Ensembl:ENSPCOP00000010338.1};
OS Propithecus coquereli (Coquerel's sifaka) (Propithecus verreauxi
OS coquereli).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lemuriformes;
OC Indriidae; Propithecus.
OX NCBI_TaxID=379532 {ECO:0000313|Ensembl:ENSPCOP00000010338.1, ECO:0000313|Proteomes:UP000233160};
RN [1] {ECO:0000313|Ensembl:ENSPCOP00000010338.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (MAR-2025) to UniProtKB.
CC -!- FUNCTION: Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes
CC B-cell survival and plays a role in the regulation of humoral immunity.
CC Activates NF-kappa-B and JNK. {ECO:0000256|ARBA:ARBA00054809}.
CC -!- SUBUNIT: Associates with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.
CC {ECO:0000256|ARBA:ARBA00065494}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004183}; Single-
CC pass type III membrane protein {ECO:0000256|ARBA:ARBA00004183}.
DR RefSeq; XP_012503068.1; XM_012647614.1.
DR AlphaFoldDB; A0A2K6F8M8; -.
DR STRING; 379532.ENSPCOP00000010338; -.
DR Ensembl; ENSPCOT00000020916.1; ENSPCOP00000010338.1; ENSPCOG00000016633.1.
DR GeneID; 105813035; -.
DR KEGG; pcoq:105813035; -.
DR CTD; 608; -.
DR GeneTree; ENSGT00940000154485; -.
DR OMA; CHLRCSN; -.
DR OrthoDB; 59623at9443; -.
DR Proteomes; UP000233160; Unassembled WGS sequence.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0002260; P:lymphocyte homeostasis; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:InterPro.
DR CDD; cd13414; TNFRSF17; 1.
DR FunFam; 4.10.1290.10:FF:000003; Tumor necrosis factor receptor superfamily member 17; 1.
DR Gene3D; 4.10.1290.10; Tumor necrosis factor receptor superfamily; 1.
DR InterPro; IPR015337; BCMA_Tall-1-bd.
DR InterPro; IPR043521; TNFR_13C/17.
DR InterPro; IPR022320; TNFR_17.
DR PANTHER; PTHR20437; TUMOR NECROSIS FACTOR RECEPTOR SUBFAMILY MEMBER 13/17; 1.
DR PANTHER; PTHR20437:SF0; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 17; 1.
DR Pfam; PF09257; BCMA-Tall_bind; 1.
DR PRINTS; PR01967; TNFACTORR17.
DR SUPFAM; SSF57586; TNF receptor-like; 1.
PE 4: Predicted;
KW Adaptive immunity {ECO:0000256|ARBA:ARBA00023130};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW Immunity {ECO:0000256|ARBA:ARBA00022859};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW Receptor {ECO:0000256|ARBA:ARBA00023170};
KW Reference proteome {ECO:0000313|Proteomes:UP000233160};
KW Signal-anchor {ECO:0000256|ARBA:ARBA00022968};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|SAM:Phobius}.
FT TRANSMEM 53..76
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 8..44
FT /note="BCMA TALL-1 binding"
FT /evidence="ECO:0000259|Pfam:PF09257"
SQ SEQUENCE 183 AA; 20174 MW; B31C26721F842E20 CRC64;
Query Match 80.4%; Score 239.5; Length 183;
Best Local Similarity 83.3%;
Matches 45; Conservative 2; Mismatches 6; Indels 1; Gaps 1;
Qy 1 MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA 54
| ||| || |||||||||||| || ||| |:|||| |||||||:||||||||||
Db 1 MFQMARQCFQNEYFDSLLHACKPCHLRC-SDTPPLICQRYCNANVTNSVKGTNA 53
Conclusion
16. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
17. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
July 6, 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
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