DETAILED ACTION
Status of Application
Claims 1-16 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 § 818.03(a)).
Applicant’s election without traverse of Group I, claims 1-13, drawn in part to a VH3 binding polypeptide derived from a Staphylococcus Protein A (SpA) or any domain thereof, and a VH3 binding polypeptide multimer, as submitted in communication filed on 07/27/2026 is acknowledged.
Claims 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/27/2026.
The species election, in the reply filed on 07/27/2026, made without traverse for the following species: Species Group 1: SEQ ID NO: 15
Species Group 2: SEQ ID NO: 88
Species Group 3: SEQ ID NO: 177
Species Group 4: at least 60%
Claims 1-13 are at issue and will be examined to the extent they encompass the elected invention.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to UNITED KINGDOM 2203478.9 filed on 03/14/2022. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
This is the US national application which entered the national stage from
Application No. PCT/EP2023/056401 filed on 03/14/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/10/2024
is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings submitted on 09/10/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Claim Objections
Claims 1-13 are objected due to the recitation of “VH3”. Abbreviations, unless otherwise obvious and/or commonly used in the art, should not be recited in the claims without at least once reciting the entire phrase for which the abbreviation is used. Appropriate correction is required.
Claim 1 is objected to due to the recitation of “VH3 binding polypeptide derived from a Staphylococcus Protein A (SpA) or any domain thereof”. It should be amended to recite “A VH3 binding polypeptide derived from Staphylococcus Protein A (SpA) or any domain thereof”. Appropriate correction is required.
Claim 2 is objected due to the recitation of “…comprising a sequence A, which Sequence A consists of…”. It should be amended to recite “…comprising sequence A, in which Sequence A consists of…”. Appropriate correction is required.
Claim 2 is objected to due to the recitation of of “…ii) an amino acid sequence which has at least 83 % identity to a sequence defined by i) iii) an amino acid sequence which has at least 70% identity to any sequence…”. It should be amended to have an “and” between parts ii) and iii). Appropriate correction is required.
Claims 2-11 and 13 are objected to due to the recitation of “VH3 binding polypeptide according to…”. It should be amended to recite “The VH3 binding polypeptide according to…”. Appropriate correction is required.
Claim 11 is objected to due to the recitation of “VH3 binding polypeptide multimer”. It should be amended to recite “A VH3 binding polypeptide multimer”. Appropriate correction is required.
Claim 12 is objected to due to the recitation of “VH3 binding polypeptide multimer according to claim 11”. It should be amended to recite “The VH3 binding polypeptide multimer according to claim 11”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
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.
Claims 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claims recite in part a VH3 binding polypeptide derived from a Staphylococcus Protein A (SpA) or any domain thereof, which is not markedly different from the naturally occurring protein of El-Sayed et al. (See alignment below). It is noted that SEQ ID NO: 88 of this instant case and the sequence of El-Sayed et al. were aligned. This judicial exception is not integrated into a practical application because claims 1-13 encompass a naturally occurring protein. As shown in the alignment below, El-Sayed et al. disclose a polypeptide derived from Staphylococcus Protein A (SpA) comprising a VH3 polypeptide sequence encompassed by the instant claims, and the combination of additional elements fails to integrate the judicial exception into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the limitations do not convey any markedly different structural differences between a man-made and a naturally occurring product.
RESULT 1
Q70AB8_STAAU
ID Q70AB8_STAAU Unreviewed; 252 AA.
AC Q70AB8;
DT 05-JUL-2004, integrated into UniProtKB/TrEMBL.
DT 05-JUL-2004, sequence version 1.
DT 10-JUN-2026, entry version 77.
DE RecName: Full=Immunoglobulin G-binding protein A {ECO:0000256|ARBA:ARBA00021989};
DE AltName: Full=Staphylococcal protein A {ECO:0000256|ARBA:ARBA00032569};
DE Flags: Fragment;
GN Name=spa {ECO:0000313|EMBL:CAE54483.1};
OS Staphylococcus aureus.
OC Bacteria; Bacillati; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280 {ECO:0000313|EMBL:CAE54483.1};
RN [1] {ECO:0000313|EMBL:CAE54483.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=M2 {ECO:0000313|EMBL:CAE54483.1};
RA El-Sayed A., Alber J., Laemmler C., Abdulmawjood A., Zschoeck M.;
RT "Size and sequence variations of spa gene of Staphylococcus aureus isolated
RT from bovine mastitis.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EMBL:CAE54483.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=M2 {ECO:0000313|EMBL:CAE54483.1};
RA El-Sayed A.;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0007829|PDB:2B87, ECO:0007829|PDB:2B88}
RP STRUCTURE BY NMR OF 116-173.
RX PubMed=16750222; DOI=10.1016/j.jmb.2006.04.043;
RA Lendel C., Dogan J., Hard T.;
RT "Structural basis for molecular recognition in an affibody:affibody
RT complex.";
RL J. Mol. Biol. 359:1293-1304(2006).
CC -!- FUNCTION: Plays a role in the inhibition of the host innate and
CC adaptive immune responses. Possesses five immunoglobulin-binding
CC domains that capture both the fragment crystallizable region (Fc
CC region) and the Fab region (part of Ig that identifies antigen) of
CC immunoglobulins. In turn, Staphylococcus aureus is protected from
CC phagocytic killing via inhibition of Ig Fc region. In addition, the
CC host elicited B-cell response is prevented due to a decrease of
CC antibody-secreting cell proliferation that enter the bone marrow,
CC thereby decreasing long-term antibody production. Inhibits osteogenesis
CC by preventing osteoblast proliferation and expression of alkaline
CC phosphatase, type I collagen, osteopontin and osteocalcin. Acts
CC directly as a pro-inflammatory factor in the lung through its ability
CC to bind and activate tumor necrosis factor alpha receptor 1/TNFRSF1A.
CC {ECO:0000256|ARBA:ARBA00045965}.
CC -!- SUBUNIT: Interacts with host TNFRSF1A; this interaction leads to the
CC stimulation of both surface expression and shedding of TNFRSF1A.
CC Interacts (via B domain) with IgG1, IgG2 and IgG4; spa interferes with
CC IgG oligomerization and IgG:C1 complement complex formation, preventing
CC complement activation and ultimately protecting bacteria from
CC phagocytic killing. {ECO:0000256|ARBA:ARBA00094865}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000256|ARBA:ARBA00004168}; Peptidoglycan-anchor
CC {ECO:0000256|ARBA:ARBA00004168}.
CC -!- SIMILARITY: Belongs to the immunoglobulin-binding protein SpA family.
CC {ECO:0000256|ARBA:ARBA00008581}.
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DR EMBL; AJ606380; CAE54483.1; -; Genomic_DNA.
DR PDB; 2B87; NMR; -; A/B=116-173.
DR PDB; 2B88; NMR; -; A=116-173.
DR PDB; 2B89; NMR; -; A=116-173.
DR PDBsum; 2B87; -.
DR PDBsum; 2B88; -.
DR PDBsum; 2B89; -.
DR AlphaFoldDB; Q70AB8; -.
DR SASBDB; Q70AB8; -.
DR SMR; Q70AB8; -.
DR EvolutionaryTrace; Q70AB8; -.
DR GO; GO:0019865; F:immunoglobulin binding; IEA:InterPro.
DR FunFam; 1.20.5.420:FF:000003; Immunoglobulin G-binding protein A; 3.
DR Gene3D; 1.20.5.420; Immunoglobulin FC, subunit C; 4.
DR InterPro; IPR009063; Ig/albumin-bd_sf.
DR InterPro; IPR003132; Protein_A_Ig-bd.
DR Pfam; PF02216; B; 4.
DR SUPFAM; SSF46997; Bacterial immunoglobulin/albumin-binding domains; 4.
PE 1: Evidence at protein level;
KW 3D-structure {ECO:0007829|PDB:2B87, ECO:0007829|PDB:2B88};
KW Cell wall {ECO:0000256|ARBA:ARBA00022512};
KW Peptidoglycan-anchor {ECO:0000256|ARBA:ARBA00023088};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Virulence {ECO:0000256|ARBA:ARBA00023026}.
FT DOMAIN 2..53
FT /note="Protein A Ig-binding"
FT /evidence="ECO:0000259|Pfam:PF02216"
FT DOMAIN 59..111
FT /note="Protein A Ig-binding"
FT /evidence="ECO:0000259|Pfam:PF02216"
FT DOMAIN 117..169
FT /note="Protein A Ig-binding"
FT /evidence="ECO:0000259|Pfam:PF02216"
FT DOMAIN 175..227
FT /note="Protein A Ig-binding"
FT /evidence="ECO:0000259|Pfam:PF02216"
FT REGION 33..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:CAE54483.1"
FT NON_TER 252
FT /evidence="ECO:0000313|EMBL:CAE54483.1"
SQ SEQUENCE 252 AA; 28335 MW; CB98408078074DB2 CRC64;
Query Match 88.2%; Score 255; Length 252;
Best Local Similarity 89.5%;
Matches 51; Conservative 1; Mismatches 5; Indels 0; Gaps 0;
Qy 2 DAKFDKEAQEAFYEILHLPNLTEEQRNAFIQSLKDDPSVSKAILAEAKKLNDAQAPK 58
| ||:|| | ||||||||||||||||| ||||||||||||| |||||||||||||||
Db 175 DNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPK 231
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 (claims 3-10, 12-13 dependent thereon) is indefinite in the recitation of “X8X9XioXi1AX13X4X5X16X7X18X19PNLX23X24X25 X26RX28X29FIQSLX35X36 (SEQ ID NO:95)”, for the following reason: SEQ ID NO:95 in the sequence listing is XXXXAXXXXX XXPNLXXXXR XXFIQXLXX. Therefore, it is unclear if the S at position 26 is required in this case. Correction is required.
Claim 2 (claims 3-10 dependent thereon) is indefinite in the recitation of “ii) an amino acid sequence which has at least 83 % identity to a sequence defined by i)”, for the following reason: It is unclear if the amino acid sequence of ii) requires the amino acids required at positions X8, X15, X16….X36 that are recited in part i), or if the variant having at least 83% is not required to have the amino acid residues at the positions recited in i). For examination purposes, no patentable weight will be given to part ii). Correction is required.
Claim 2 (claims 3-10 dependent thereon) is indefinite in the recitation of “wherein additionally, in each of i), ii) and iii)…X9 is selected from Q, Y, and A…..X29 is selected from A and G”, for the following reason: X9, X10….and X29 are only recited in part i) of claim 1. There is no X9, X10….X29 recited in parts ii) or iii). Thus, it is unclear as to how these amino acid requirements at X9, X10…X29 can be applied to parts ii) or part iii). Please note that the preamble of claim 1 requires only one of i), ii) or iii). Therefore, limitations regarding X9, X10…X29 only applies to part i). Correction is required.
Claims 2, 4, 7, 10, and 12-13 (claims 3, 5-6, and 8-9 dependent thereon) are indefinite in the recitation of “such as”, for the following reason: The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For examination purposes, no patentable weight will be given to the limitations following the phrase “such as”. Correction is required.
Claim 4 is indefinite in the recitation of “X9X10X11X13X14 is selected from….AQRLA and AYRLA”, for the following reason: The term implies that the polypeptide of claim 2 comprises a peptide having the sequence AQRLA or AYRLA. However, according to claim 2, part i) there is an alanine between X11 and X13. Moreover, there is no consecutive fragment in part i) that has X9X10X11X13X14. Therefore, the polypeptide of claim 4 is not further limiting
the polypeptide of claim 2. For examination purposes, claim 4 will be interpreted as a duplicate of claim 2. Correction is required.
Claim 7 is indefinite in the recitation of “an amino acid sequence which has at least 75% identity to a sequence defined by iv)”, for the following reason: It is unclear if the amino acid sequence of v) should have the required amino acids at positions X40, X42….X54 listed in part iv), or if the amino acid sequence of v) can have other amino acid residues at positions X40, X42…X54 listed in part iv). For examination purposes, no patentable weight will be given to to part v). Correction is required.
Claim 8 is indefinite in the recitation of “…comprising a binding module sequence C, which sequence c consists of sequence A according to claim 2 and sequence B in the following order…”, for the following reason: there is no mention in claim 2 for sequence B. Therefore, it is unclear as to what sequence B should be. For examination purposes, the claim will be interpreted as the VH3 binding polypeptide of claim 2 having an amino acid sequence at least 70% identical to residues 8-54 of SEQ ID NO: 88. Correction is required.
Claim 10 is indefinite in the recitation of “wherein sequence vi) or viii)”, for the following reason: There is no antecedent basis in claim 2 for sequence vi) or viii). For examination purposes, claim 10 will be interpreted as a duplicate of claim 2. Correction is required.
Claim 11 (claim 12 dependent thereon) is indefinite in the recitation of “and wherein the multimer preferably is…”, for the following reason: It is unclear if the phrase that follows the term is intended to further limit the claim. For examination purposes, no patentable weight will be given to the term “and wherein the multimer is preferably….”. Correction is required.
Claim 13 is indefinite in the recitation of “at least 95% of the alkali clean stability of SEQ ID NO: 88 after…”, for the following reason: SEQ ID NO: 88 is an amino acid sequence. An amino acid sequence is the graphical representation of the order in which amino acids are arranged in a polypeptide. Therefore, it cannot have any activity or alkali clean stability. If the intended limitation is “at least 95% of the alkali clean stability of the polypeptide of SEQ ID NO: 88 after…”, the claim should be amended accordingly. Correction is required.
Claim 11 (claim 12 dependent thereon) is indefinite in the recitation of “each monomer of the multimer comprises a VH3 binding polypeptide which is independently selected from any VH3 binding polypeptide defined in claim 1”, for the following reason: VH3 binding polypeptides are not defined in claim 1 to be independently selected. Therefore, it is unclear what VH3 binding polypeptides are being selected in this case. For examination purposes, “selected from any VH3 binding polypeptide defined in claim 1” will be interpreted as “selected from any VH3 binding polypeptide defined in claim 2”. Correction is required.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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, 11, and 13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow.
Claims 1, 11, and 13 are directed in part to a VH3 binding polypeptide, having any structure, derived from a Staphylococcus Protein A (SpA) or any domain thereof, wherein said polypeptide has binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile. See claim rejections under 35 usc 112(b) for claim interpretation.
As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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.
While the specification in the instant application discloses the structure of a limited number of VH3 binding polypeptides, it provides no clue as to the structural elements required in any VH3 binding polypeptide that has binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile. Neither the specification nor the prior art disclose the structural features of the VH3 binding polypeptides required that have binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which VH3 binding polypeptides have the claimed function.
The claims encompass a large genus of proteins which are structurally unrelated or substantially unrelated. A sufficient written description of a genus of polypeptides may be achieved by a recitation of a representative number of polypeptides defined by their amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is either no recited structural feature which is representative of all the members of the genus of VH3 binding polypeptides recited in the claim, or the recited structural feature. The current disclosure is not representative of all the members of the genus of VH3 binding polypeptides recited since there is no information as to which are the structural elements within the polypeptide that are essential for the desired function, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired function is displayed, or a correlation between structure and function which would provide those unknown structural features. While one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation (Abstract), therefore having different function. Since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all required by the claim. Therefore, one of ordinary skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1, 11, and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for VH3 binding polypeptides with sequences selected from the group consisting of SEQ ID NO: 1-82. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1, 11, and 13 broadly encompass a VH3 binding polypeptide, having any structure, derived from a Staphylococcus Protein A (SpA) or any domain thereof, wherein said polypeptide has binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the common structural element required for a VH3 binding polypeptide, having any structure, derived from a Staphylococcus Protein A (SpA) or any domain thereof, to have binding affinity for a VH3 region of trastuzumab, and have lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO: 88 for the same Fc region, and be alkali clean stabile. In the instant case, the specification enables VH3 binding polypeptides with sequences selected from the group consisting of SEQ ID NO: 1-82.
The amount of direction or guidance presented and the existence of working examples. The specification discloses VH3 binding polypeptides with sequences selected from the group consisting of SEQ ID NO: 1-82. However, the specification fails to provide any clue as to the structural elements required in a VH3 binding polypeptide, having any structure, derived from a Staphylococcus Protein A (SpA) or any domain thereof, wherein said polypeptide has binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile. No correlation between structure and function has been presented.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The structure of a polypeptide determines its activity and functional properties. While the art discloses a limited number of VH3 polypeptides, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of a VH3 polypeptide that has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO: 88 for the same Fc region and can be alkali clean stabile. The art clearly teaches that even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation (Abstract), therefore having different functions.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of determining polypeptide function and proteins activity were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of VH3 polypeptides with different structures to find a polypeptide with the desired function. In the absence of (i) a rational and predictable scheme for selecting those polypeptide most likely to have the desired functional features, (ii) a correlation between structure and the recited function, one of skill in the art would have to test an infinite number of VH3 polypeptides.
Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability in the prior art, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Claim Rejections - 35 USC § 102 (AIA )
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.
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 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.
Claims 1-2, 4, 6-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by El-Sayed et al. (GenBank accession No. CAE54483.1, 7/26/2016; hereby El-Sayed).
Claims 1-2, 4, 6-10 are directed in part to a VH3 binding polypeptide derived from a Staphylococcus Protein A (SpA) or any domain thereof, wherein said polypeptide has binding affinity for a VH3 region of trastuzumab, and has lower binding affinity for an Fc region of trastuzumab, compared to the binding affinity of SEQ ID NO:88 for the same Fc region and wherein said VH3 binding polypeptide is alkali clean stabile; wherein the VH3 binding polypeptide comprises a sequence A, in which Sequence A consists of amino acid sequence i) X8X9XioXi1AX13X4X5X16X7X18X19PNLX23X24X25 X26RX28X29FIQSLX35X36 (SEQ ID NO:95) wherein, independently from each other, X8 is selected from E, D and A; X15 is selected from E and Q; X16 is selected from I and V; X19 is selected from L and M; X23 is selected from N and T; X24 is selected from A and E, such as is E; X25 is selected from D and E, such as is E; X35 is selected from K, R and H; X36 is selected from D and H; wherein sequence i) corresponds to the sequence from position 8 to position 36 in a sequence selected from the group consisting of SEQ ID NO:1-82; wherein the VH3 binding polypeptide according to claim 2, further comprises a Sequence B arranged C-terminally of said sequence A, which Sequence B consists of amino acid sequence iv) DPSX4oSX42X43 X44LX46EAX49X50LNX53X54 (SEQ ID NO:96) wherein, independently from each other,X4o is selected from Q, T and V;X42 is selected from A, K, L and T;X43 is selected from N, E, A, and S;X44 is selected from L, I and V;X46 is selected from A, G, S and K, such as from A, S and K;X49 is selected from K and Q, such as is K;X50 is selected from K and R;X53 is selected from D, E and K; andX54 is selected from A and S; wherein the VH3 binding polypeptide according to claim 2, comprise a binding module sequence C, which Sequence C consists of Sequence A according to claim 2 and Sequence B in the following order from the N-terminus to the C-terminus [Sequence A]-[Sequence B]; wherein the VH3 binding polypeptide according to claim 2, comprising a binding module Sequence C selected from the group consisting of: viii) [Sequence A]-DPSVSKAILAEAKKLNDA (SEQ ID NO: 115); wherein [Sequence A] is as defined in claim 2; ix) an amino acid sequence which has at least 85 % identity to the sequence defined in viii). It is noted that claim 4 and 10 are interpreted as duplicates of claim 2 (see 112b rejections).
As shown in the alignment above, El-Sayed discloses a polypeptide derived from a Staphylococcus Protein A (SpA) comprising of a VH3 polypeptide sequence encompassed by the instant claims. Regarding claims 1-2, 4, and 10, the sequence of El-Sayed has SEQ ID NO: 95 (in bold with no underline), wherein, independently from each other, X8 is E, X15 is E, X16 is I, X19 is L, X23 is T, X24 is E, X25 is E, X35 is K, and X36 is D. It is noted that limitations regarding the polypeptide being alkaline clean stabile and having the recited binding affinity are inherent to the protein of El-Sayed, in view of the Applicant’s assertions that proteins that have the recited amino acids have this property. Regarding claim 6, it is noted that this claim only states that the amino acid sequence of SEQ ID NO: 95 corresponds to any of the sequences listed (1-82); it is not saying that the VH3 polypeptide must comprise any of SEQ ID NO: 1-82. Therefore, claim 6 is not limiting the VH3 binding polypeptide structurally. Regarding claim 7, the sequence of El-Sayed has SEQ ID NO: 96 of this instant case (in bold with underline), wherein, independently from each other, X40 is V, X42 is K, X43 is E, X44 is I, X46 is A, X49 is K, X50 is K, X53 is D, and X54 is A. Regarding claim 8, El-Sayed has Sequence A and Sequence B of this instant case connected in the order of [Sequence A]-[Sequence B]. Regarding claim 9, SEQ ID NO: 115 has 1 mismatch compared to the bold fragment of El-Sayed. Therefore, the polypeptide of El-Sayed anticipates the instant claims as written/interpreted.
Conclusion
No claim is in condition for allowance.
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/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
