DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
The preliminary amendment filed 04/10/2024 is entered. Claims 1-10 are pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Therefore, the effective filing date of the instant application is 04/09/2021, which is the filing date of the foreign priority document.
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).
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.
Specification
The disclosure is objected to because of the following informalities:
The description of the drawings on pages 4-6 contain references to color features which are required to understand and distinguish critical features in the figures; however, the figures do not depict color features or otherwise depict or label these features so that they can be understood from the specification. Therefore, the specification does not describe essential features of the drawings. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-10 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.
Regarding claim 1, the phrase "preferably" 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). Claims 2-10 depend on claim 1 and fail to resolve the indefinite language.
Additionally regarding claims 3, 4, and 8, a second usage of the phrase "preferably" 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). Claims 9-10 depend on claim 8 and fail to resolve the indefinite language.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (Wang, Z. et al, BirA*-protein A fusion protein based BioEnhancer amplifies western blot immunosignal, Electrophoresis 2021, 42, 793–799, published 03/2021).
Regarding claim 1, Wang et al teaches a fusion polypeptide comprising a biotin ligase enzyme fused to an immunoglobulin-binding bacterial protein, Protein A (Abstract).
Claim 2 depends on claim 1. The teachings of Wang et al regarding claim 1 is incorporated in its entirety for claim 2, and further described, as is relevant to each claim, below.
Regarding claim 2, Wang et al further teaches that biotin ligase enzyme in the fusion polypeptide has proximity-dependent biotinylation activity (Abstract and Introduction, paragraphs 2 and 4).
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 3-10 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al as applied to claim 1 above in view of Farrell et al (US 9663814 B2, Farrell, M. et al, Proximity Assay for In Situ Detection of Targets, effectively filed 03/12/2013), and further in view of Choe et al (Choe, W. et al, Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides, Materials 2016, 9, 994, published 12/08/2016).
Claims 3-10 depend on claim 1. The teachings of Wang et al regarding the fusion polypeptide of claim 1 is incorporated in its entirety for claims 3-10, and further described, as is relevant to each claim, below.
Regarding claims 3-5, Wang et al further teaches an antibody directs the fusion polypeptide to the antibody target by way of the immunoglobulin-binding bacterial protein in the fusion polypeptide binding to the antibody (see section 3.2 BioEnhancer recognized IgG and added biotin tags to its proximal proteins, paragraph 3; and section 4.1 BioEnhancer inherits the primary antibody binding specificity). Wang et al teaches the fusion polypeptide and antibody are in a composition with the target (see section 3.2 BioEnhancer recognized IgG and added biotin tags to its proximal proteins, paragraph 3).
Regarding claims 6-10, Wang et al further teaches a method of biotinylating a protein of interest and a method of proximity labeling of proteins in a sample of interest, wherein the method comprises of contacting or introducing the antibody and fusion polypeptide to its target protein and adding or contacting the target protein with biotin and ATP, wherein the antibody targets the fusion polypeptide to a target, and the biotin ligase biotinylates the antibody target protein or proteins in proximity to the biotin ligase (see section 3.2 BioEnhancer recognized IgG and added biotin tags to its proximal proteins, paragraph 3).
Regarding claims 4, Wang et al does not explicitly teach the antibody and fusion polypeptide is complexed before targeting to the antibody target.
Regarding claims 8-10, Wang et al does not explicitly teach a kit for biotinylating a protein of interest, comprising of the fusion polypeptide of claim 1 and an immunoglobulin. Regarding claims 10, Wang et al does not explicitly teach the kit further comprises of biotin or a derivative thereof, and ATP.
Regarding claim 3, 5-7, and 9 Wang et al does not explicitly teach the antibody targets the fusion polypeptide to a protein in a cell or subcellular region of interest.
However, Farrell et al also teaches the concept of biotin ligase targeted by an antibody for proximity-based biotinylation (Abstract, Figure 2). Farrell et al differs from the instant application claims by how the biotin ligase is bound to the antibody, as Farrell et al conjugates the thiol on the biotin ligase to a maleimide on the antibody, (Column 29, lines 60-67- Column 30, lines 55-56) instead of using an immunoglobulin-binding bacterial protein fused to the biotin ligase.
Farrell et al teaches that the antibody and biotin ligase are complexed before targeting the biotin ligase to the antibody target (Column 29, lines 60-67- Column 30, lines 55-56), as is relevant to claim 4.
Farrell et al teaches a kit for biotinylating a protein of interest, comprising of a biotin ligase, an antibody, and further comprising biotin and ATP (Column 52, section VIII. Kits), as is relevant to claims 8-10.
Farrell et al teaches that the targets for biotinylation can be in any cellular compartment (Column 2, line 3), which includes in a cell and subcellular regions, as is relevant to claims 3, 5-7, and 9.
Regarding claim 5, although Wang et al teaches the immunoglobulin-binding bacterial protein is Protein A, Wang et al and Farrell et al do not explicitly teach the immunoglobulin-binding bacterial protein binds to the Fc region of an IgG.
Regarding 1-10, Wang et al and Farrell et al do not explicitly teach the motivation of using an immunoglobulin-binding bacterial protein as the method for binding a biotin ligase to an antibody for proximity-based biotinylation, as opposed to other methods of binding a biotin ligase to an antibody.
However, Choe et al further teaches that Protein A binds to the Fc region of IgG (Section 2. Immunoglobulin Binding Proteins, paragraph 1), as is relevant to claim 5.
Choe et al further teaches the motivation of using an immunoglobulin-binding bacterial protein as the method for binding a ligand, such as a biotin ligase, to an immunoglobulin. Choe et al teaches that when an antibody is to be used in applications requiring binding to its cognate antigen, it is crucial that the Fab region of the antibody is not disturbed in order to enable binding of its cognate antigen (Section 1. Introduction, paragraph 2). As such, immunoglobulin-binding proteins that bind Fc regions of immunoglobulins are useful for these purposes.
One skilled in the art, before the effective filing date of the instant application, would be motivated to improve on the base structure of the biotin ligase and antibody complex for proximity-dependent biotinylation taught by Farrell et al to the structure taught by Wang et al, arriving at all the limitations of the claimed invention, based on the teachings of Choe et al that Fc-binding ligands are preferred for antibody conjugation when the antibody will be used for its binding function, as is the case in these references, since avoiding conjugation to the Fab region helps avoid disturbing the antibody's binding function. Since the thiol-maleimide chemistry method of conjugation taught in Farrell et al is not specifically directed away from the Fab region of an antibody, but the immunoglobulin-binding bacterial protein taught by Wang et al, Protein A, is directed to the Fc region of IgG, and the antibody will be used for its targeting function, one skilled in the art, before the effective filing date of the instant application, would be motivated to adopt the structure taught by Wang et al in order to not disturb the binding activity of the antibody, which is crucial to the method of targeted biotinylation.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with this improvement as the difference in conjugation strategy does not hinder the proximity-dependent biotinylation function of the antibody and biotin ligase, and they would both function as taught by Wang et al and Farrell et al. Farrell et al differs from the instant application and Wang et al by how the biotin ligase is bound to the antibody. The conjugation method effects the location of labeling of the antibody, but the methods in both references yielded antibodies that could still target, although the immunoglobulin-binding bacterial protein is a more desirable choice for this application as taught by Choe et al. Additionally, the conjugation method effects the order of binding between the different components in the method. The structure as taught by Farrell et al, using the thiol-maleimide chemistry to attach the biotin ligase to the antibody, teaches this structure complexed together before introduction to its target sample of interest. The structure as taught by Wang et al teaches the antibody and biotin ligase can be introduced to the target sample of interest as a composition, without complexing to each other first. However, it is possible to also complex the polypeptide to antibody before introduction to the target sample of interest.
The impact of the conjugation method between the biotin ligase and antibody has been shown to not preclude the functions of the biotin ligase and antibody, although the method used by Wang et al and the instant application theoretically precludes the antibody's function less than the method used by Farrell et al. Specifically, the differences in conjugation method does not preclude the structure taught by Wang et al from effectively functioning in a subcellular region, as taught for the similar structure taught by Farrell et al, in light of the teachings of Choe et al outlining the use of immunoglobulin-binding bacteria proteins in labeling antibodies for delivery into live cells (see, for example, Figure 8a). The differences in conjugation method does not preclude the structure taught by Wang et al to be placed into a kit as taught by Farrell et al, as there are methods to store and maintain the immunoglobulin-binding bacterial protein function, as is evidenced by the use of these binding proteins in antibody purification chromatography columns (Choe et al, Abstract). The antibody directed biotin ligase would therefore be expected to function as described in both references, meeting all the claimed limitations of the instant application.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of known technique to improve similar products or methods in the same way are obvious. In this case, the base product and method as taught by Farrell et al comprises of a biotin ligase bound to an antibody, wherein this complex is used for proximity-dependent biotinylation of proteins, wherein the components of the complex can also be made into a kit. This product enables a method of proximity labeling of proteins wherever the antibody can be directed to, including a subcellular region of interest. Wang et al teaches a comparable product as Farrell et al and the instant application, comprising of a biotin ligase bound to an antibody by an immunoglobulin-binding bacteria protein. Choe et al provides the motivation to improve on the conjugation method of the biotin ligase and antibody without abrogating the functions of either and possibly enhance the antibody targeting function. The end product for both is a biotin ligase that can be directed by an antibody to a protein of interest. The structure of Wang et al meets the limitations of the claimed structure and has all the functional capabilities taught by both Wang et al and Farrell et al due to their shared functional features, meeting the limitations of the instant application.
Conclusion
No claims have been allowed.
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/B.C./Examiner, Art Unit 1645 January 22, 2026
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645