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 .
The Applicants’ Amendment to the Claims filed on 11/10/2025 is entered.
Claims 8-10, 14-15, 20-22, 24-25, 27, and 29-44 are cancelled.
Claims 45-47 are new.
Claims 1-7, 11-13, 16-19, 23, 26, 28, and 45-47 are pending and under examination.
Election/Restrictions
Applicant’s election without traverse of invention Group I (e.g., claims 1-7, 11-13, 16-19, 23, 26, 28, and 45-47) in the reply filed on 11/10/2025 is acknowledged.
Applicant’s election without traverse of the following species in the reply filed on 11/10/2025 is acknowledged:
A) 2-Bromoethylamine hydrobromide;
B) VTVSSASTK (SEQ ID NO:1);
C) protein G-conjugated beads;
D) trypsin;
E) pepsin;
F) VH CDR1: GFSLSSY (SEQ ID NO:5);
VH CDR2: DANDY (SEQ ID NO:6);
VH CDR3: YSRDGAIDPYFKI (SEQ ID NO:7);
VL CDR1: QSSQSVAGNRWAA (SEQ ID NO:8);
VL CDR2: QASKVTS (SEQ ID NO:9); and
VL CDR3: AGGYSGEFWA (SEQ ID NO: 10).
Priority
This is the First Office Action on the Merits of US 18/009,304 filed on 12/08/2022 which is a 371 of PCT/CA2021/050791 filed on 06/10/2021 which claims US Priority benefit of US Provisional 63/038,069 filed on 06/11/2020. The Filing Receipt filed on 03/23/2023 is controlling.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See: page 10, lines 20 and 34; page 20, line 17; page 25, line 35; page 43, line 1.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See FIG1, FIG2, FIG7, FIG10.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Information Disclosure Statement
The IDS statements filed on 01/31/2023, 12/08/2022, and 3/16/2026 have been considered by the examiner.
Specification
The use of the terms Promega, FLAG, ProteoWizard, and Orbitrap Fusion Lumos which are trade names or a marks used in commerce, have been noted in this application. (For example, see pages 22, and 42). The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 16, 18, and 26 are objected to because of the following informalities:
In claim 16, for improved clarity, amend as follows: …wherein the endoprotease is trypsin, a trypsin-like endoprotease, a Lys-C protease, a Lys-N protease, a Asp-N protease, a Glu-C protease, a Pro/Ala protease, Sap9, KEX2, IdeS or IdeZ.
In claim 18, for improved clarity, amend as follows: …wherein the second protease is pepsin, chymotrypsin, proteinase K, a Glu-C protease or an Asp-N protease.
Regarding claim 26, the phrase “…sample is obtained from a subject from an infection, an autoimmune disease, a cancer, or from a vaccinated subject” is confusing and should be reworded for clarification. For purpose of examination claim 26 is construed to mean “…sample is obtained from a subject having an infection, an autoimmune disease, or a cancer, or from a vaccinated subject”.
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.
Claims 1-7, 11-13, 16-19, 23, 26, 28, and 45-47 are rejected under 35 U.S.C. 112(a) 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 full-scope of the claimed invention.
The present claims are drawn to a method for obtaining a sample enriched in peptides comprising the third CDR of the heavy chain (CDRH3) of a mammalian immunoglobulin of the IgG class. The method requires the critically essential element of an anti-CDRH3 peptide antibody or antigen-binding fragment thereof that specifically binds to an epitope of the sequence VTVSSASTK (SEQ ID NO:1), thereby forming complexes of the anti-CDRH3 peptide antibody and the CDRH3 peptides present in the peptide-comprising sample of interest. Note that the present claims recite that the anti-CDRH3 peptide antibody is a monoclonal antibody comprising the following combination of complementarity-determining regions (CDRs):
VH CDR1: GFSLSSY (SEQ ID NO:5) or a variant thereof having one mutation;
VH CDR2: DANDY (SEQ ID NO:6) or a variant thereof having one mutation;
VH CDR3: YSRDGAIDPYFKI (SEQ ID NO:7) or a variant thereof having one mutation;
VL CDR1: QSSQSVAGNRWAA (SEQ ID NO:8) or a variant thereof having one mutation;
VL CDR2: QASKVTS (SEQ ID NO:9) or a variant thereof having one mutation; and
VL CDR3: AGGYSGEFWA (SEQ ID NO:10) or a variant thereof having one mutation.
Thus, the critically essential element of the anti-CDRH3 peptide antibody encompasses embodiments of variant amino acid sequences within the CDR region.
Vas-Cath, 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". For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California V. Ell Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), "[claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. V. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
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.
Both the instant specification and the state of the art have been considered.
A review of the state of the art provides evidence that that minor amino acid modifications within the CDR regions on an antibody can abolish the binding activity of said antibody. As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CHI, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. 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). The state of the prior art is such that it involves testing antibodies both in vitro and in vivo to determine which antibody exhibits the desired binding activity/specificity and therapeutic activities, because even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff (Rudikoff et al., Proc Natl Acad Sci USA 1982, 79(6) 1979-1983, Publication Year: 1982). Rudikoff teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding. Even if the antibody is limited to antibody which can bind to tumor associated antigens, Riemer (Riemer et al. Mol Immunol, 2005 42(9): 1121-1124, Publication Date: 2005-01-08) teaches that antibodies binding the same antigens have been shown to both ameliorate and aggravate disease symptoms (entire document, particular page 1123, column 1), indicating unpredictability of therapeutic outcomes.
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.
The instant specification provides only two examples of the anti-CDRH3 peptide antibody but do not provide a representative set to support the numerous embodiments of functional variants encompassed by the claims. Specifically, the present specification provides an antibody or antigen-binding portion thereof that specifically binds to the epitope of the sequence VTVSSASTK. Antibodies PD030 rl and PD030 r3 with their complete 6 CDRs, as defined by SEQ ID NOs: 5-10 and 11-16, respectively, specifically binds to the epitope of the sequence VTVSSASTK.
In view of the state of the art and the instant specification it is considered that applicants were not in possession of an antibody or antigen-binding fragment thereof as defined in the claims, i.e. comprising variant light chain and heavy chain CDRs that comprise one mutation.
The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as be structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXlS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original).
While having written description of the two types of anti-CDRH3 peptide antibodies of claim 11, but without the variant alternatives of having one mutation, the specification does not provide sufficient descriptive support for the myriad of embodiments embraced by the claims. When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Given this lack of description of representative species encompassed by the genus of the claim, the specification does not sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the entire scope of the claimed invention.
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph. In the instant case, the unpredictability of the art is evidenced by the cited references, above. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
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 1-7, 12-13, 16-19, 23, 26, 28, and 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Lavinder et al (WO2013/078455 published May 30, 2013; IDS ref), in view of US 2010/0143949 to Petricoin et al in further view of Eggena et al "Phage display cloning and characterization of an immunogenetic marker
(perinuclear anti-neutrophil cytoplasmic antibody) in ulcerative colitis.", J. Immunol. 1996, Vol 156: pages 4005-4011).
Claim interpretation: Claims must be given their broadest reasonable interpretation in light of the specification during examination. Optional steps are construed as not required for purpose of applying prior art. Thus, optional steps (b), (c), and (d1) of claim 1 are not required for purpose of applying prior. Further, because claims 2-3 refer only to the optional step (c), these limitations are interpreted as not being required for purpose of applying prior.
Regarding claim 1, Lavinder et al disclose a method for obtaining a sample enriched in peptides comprising the CDRH3 of a mammalian immunoglobulin of the IgG class. See FIG5 below.
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Lavinder et al disclose that it “was found that CDRH3 containing peptides can be selectively enriched from other antibody proteolytic fragments by affinity chromatography using antibodies specific for J region peptides, i.e., peptides encoded by a portion of the J segment of the V(D)J locus comprising the region of the V gene adjacent to the CDRH3”. (See para bridging pages 55-56). Lavinder et al disclose that “generating peptides including intact CDRH3 regions was based on the selection of proper protease”. Lavinder et al disclose use of the endoprotease trypsin, GluC and/or LysC (See para 00192-00193)
Regarding step (a), Lavinder et al disclose providing an immunoglobulin-comprising sample. (See entire ref; FIG5). Lavinder et al discloses that anti-CDRH3-J peptide antibodies were produced in a rabbit. The CDR3-J peptide sequence was designed to exhibit amino acids from the C-terminal portion of the CDRH3 segment, full FR4, and the N-terminal portion of the constant region CH1 (FIG. 3).
Regarding step (d), Lavinder et al disclose contacting the sample with an endoprotease under conditions suitable for protein digestion to cleave the immunoglobulin into peptides and generate a peptide comprising (i) the CDRH3 and (ii) an epitope of the sequence VTVSSASTK (SEQ ID NO:1). (See para 0025; para 00147.) Lavinder et al disclose digesting the IgGs with proteases (trypsin, GluC and/or LysC). Lavinder et al discloses that generating peptides including intact CDRH3 regions was based on the selection of the proper proteases. Proteases can cleave V gene polypeptides in a manner that results in the generation of peptides that cleave N- and C-terminal of the CDR3, leaving the CDR3 sequence largely intact in most sequences (paragraph [00192].
Lavinder et al disclose that the CDR3-J peptide NH2-CGGTLVTVSSGQPK-COOH was synthesized, purified, and conjugated to KLH as a carrier and the conjugate was used to immunize chickens for IgY production (paragraph [00195], FIG. 3). Lavinder et al disclose epitopes that include the amino acid sequence VTVSS which may be construed to meet the limitation of an epitope of the amino acid sequence VTVSSASTK (SEQ ID NO: 1) but does not meet the limitation of an epitope consisting of VTVSSASTK (SEQ ID NO: 1).
Regarding step (e), Lavinder et al disclose contacting the peptide-comprising sample in (d) with an anti-CDRH3 peptide antibody or antigen-binding fragment thereof that specifically binds to the epitope, thereby forming complexes of the anti-CDRH3 peptide antibody and the CDRH3 peptides present in the sample. Lavinder et al disclose enriching the IgGs using immobilized antigen or protein-A or protein-G affinity column. (See para 176-177; 0144; page 65, Example 10, para 00218).
Regarding step (f), Lavinder et al disclose dissociating the CDRH3 peptides from the complexes, thereby obtaining a sample enriched in peptides comprising CDRH3 of an immunoglobulin. (See Fig5; ). Lavinder et al disclose enriching the IgGs using immobilized antigen or protein-A or protein-G affinity column.
Regarding claims 2-3, because claims 2-3 refer only to the optional step (c), these limitations are interpreted as not being required for purpose of applying prior. As claims are presently written, prior art applied to claim 1 also applies to claims 2-3.
Regarding claims 4-5, Lavinder et al disclose that the mammalian immunoglobulin is a mouse, sheep, rabbit, non-human primate or human immunoglobulin. (See para 0026, lines 2-3; Fig5)
Regarding claim 5, Lavinder et al disclose a human immunoglobulin. (See para 0026, lines 2-3)
Regarding claim 6-7, Lavinder et al disclose epitopes that include the amino acid sequence VTVSS which meets the limitation of an epitope of the amino acid sequence VTVSSASTK (SEQ ID NO: 1). Further, as evidenced by Eggena et al, this meets the limitation of an epitope which is inherently located in a region that overlaps the J region and the C region of the heavy chain of the Ig (or in the first 15 residues from the C region of the heavy chain of the Ig. (See Eggena et al, entire reference & Fig2(a) and SCV STIC result for Eggena et al shown just below. As evidenced by SCV SEQ ID NO:1 result for Eggena et al, they disclose that VTVSSASTK was known in the art as an amino acid sequence of the human IG heavy chain (length 121 amino acids) and was a marker for colon cancer and ulcerative colitis.
Query Match 100.0%; Score 39; Length 121;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VTVSSASTK 9
Db 111 VTVSSASTK 119
Regarding claims 12-13, Lavinder et al disclose that the anti-CDRH3 peptide antibody is bound to a solid support being standard antigen-affinity chromatography using either of protein A or protein G-conjugated agarose beads. (See para 176-177; 0144; page 65, Example 10, para 00218).
Regarding claim 16, Lavinder et al disclose digesting the IgGs with proteases including trypsin, GluC and LysC. (See para 0025; para 00147.)
Regarding claims 17-18, Lavinder et al disclose contacting the sample with a second protease wherein the second protease is pepsin. (See para 00177; 00218.)
Regarding claim 19, Lavinder et al disclose enriching the immunoglobulin-comprising sample in immunoglobulins prior to performing step b, c or d. (See para bridging pages 55-56; para 00199; Fig5.)
Regarding claims 23 and 26, Lavinder et al disclose that the immunoglobulin-comprising sample is a biological sample obtained from a subject from an infection, an autoimmune disease, a cancer, or from a vaccinated subject. (See para 0145; page 62, Example 9.)
Regarding claims 28 and 46, Lavinder et al disclose analyzing or characterizing the peptides comprising CDRH3 of an immunoglobulin obtained in step (f) by performing LC-MS/MS analysis of the enriched CDRH3 fraction. (FIG. 5; para 0145; page 62, Example 9).
Regarding claim 45, Lavinder et al disclose that the biological sample is a blood-derived sample, saliva, nasal secretion, bronchoalveolar lavage, cerebrospinal fluid or lymph. (See para 0145; page 62, Example 9
Regarding claim 47, Lavinder et al disclose determining the amino acid sequence of the CDRH3 of the peptides from the sample obtained in step (f). (See page 62, Example 9.)
However, Lavinder et al differs from the presently claimed invention because although Lavinder et al disclose the epitope of the CDR3-J peptide NH2-CGGTLVTVSSGQPK-COOH they do not explicitly disclose that the epitope consists of the sequence VTVSSASTK (instant SEQ ID NO: 1).
Petricoin et al disclose an epitope which is the identical sequence to VTVSSASTK (SEQ ID NO: 1).
Petricoin et al recites a monoclonal antibody specific for a peptide having the sequence of reference SEQ ID NO:205. See reference claim 16. Reference SEQ ID NO: 205 is identical to instant SEQ ID NO: 1 as show below:
<210> 205
<211> 9
<212> PRT
<213> Homo sapiens
<400> 205
1 Val Thr Val Ser Ser Ala Ser Thr Lys 9
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art having the cited references before the effective filing date would have been motivated to include the antibody of Petricoin et al in the method of Lavinder et al to improve binding of important epitopes of important CDRH3 regions because Lavinder et al disclose that it “was found that CDRH3 containing peptides can be selectively enriched from other antibody proteolytic fragments by affinity chromatography using antibodies specific for J region peptides, i.e., peptides encoded by a portion of the J segment of the V(D)J locus comprising the region of the V gene adjacent to the CDRH3”. (See para bridging pages 55-56).
It would have been obvious to one of ordinary skill in the art to use the monoclonal antibody of Petricoin et al because they disclose that VTVSSASTK was known in the art as an amino acid sequence of the human IG heavy chain (length 121 amino acids) and Egglena et al disclose the region was a marker for ulcerative colitis.
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to use an antibody against the epitope of VTVSSASTK to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action if appropriate:
Wine et al (PNAS February 19, 2013, vol 110 No. 8, pages 2993-2998; IDS ref). Regarding claims 1, and 2-3, Wine et al disclose a method of obtaining a sample enriched in peptides comprising CDRH3 of IgG from a mammalian serum sample, specifically rabbit serum. (See Fig 1 and legend). Wine et al disclose epitopes that include the amino acid sequence VTVSS (see Table 1; Fig3B) which meets the limitation of an epitope of the amino acid sequence VTVSSASTK (SEQ ID NO: 1). Regarding claims 2-3, because claims 2-3 refer only to the optional step (c), these limitations are interpreted as not being required for purpose of applying prior. As claims are presently written, prior art applied to claim 1 also applies to claims 2-3. Regarding claims 4, 23, and 45, Wine et al disclose that the immunoglobulin-comprising sample is a biological sample from rabbit serum. Regarding claim 5, Wang et al explicitly suggest using their method for whole blood from humans. (See page 2998, para bridging left & right col). Regarding claim 26, Wine et al suggest that the immunoglobulin-comprising sample is obtained from a subject from an infection, an autoimmune disease, a cancer, or from a vaccinated subject.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658