DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group II (claims 13, 15, 19, 25, and 37) in the reply filed on 1 June 2026 is acknowledged. The traversal is on the ground(s) that the Office Action did not show “that a serious burden would be required to examine all of the claims.” This is not found persuasive because the instant application is a 371 of a PCT application and, thus, is subject to unity of invention analysis for restrictions, which does not require a showing of search and examination burden. See MPEP 823. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-4, 8, 10, 12, 21-23, 26, 29, and 33-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1 June 2026. Claims 13, 15, 19, 25, and 37 will be examined on the merits herein.
Priority
The instant application is a 371 of application PCT/FI2022/050014 (filed 7 January 2022) and claims priority to foreign application FI 20215012 (filed 7 January 2021). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Therefore, the effective filing date of instant claims 13, 15, 19, 25, and 37 is 7 January 2021.
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 drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Specifically, the sequences in FIG. 12 are not identified by SEQ IDNOs in the figure or in the brief description of the figure. Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
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.
Claim Objections
Claim 37 is objected to because of the following informalities: in line 1, “wherein,” should be deleted. 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.
Claim 37 is 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 37 recites the term “(raw) material sample.” As written, it is unclear if “(raw)” is intended to limit the scope of material samples recited in the claim or an example material sample and therefore not required by the claim (see MPEP 2111.04: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.”). In the interest of compact prosecution, “(raw)” is interpreted as an example and not limiting the scope of material samples required by the claim. Clarification is requested.
Claim Rejections - 35 USC § 112(a)
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 13, 15, 19, 25, and 37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims are broadly drawn to a recombinant antibody or antigen binding fragment thereof that binds Staphylococcus aureus Enterotoxin A and methods of use. Claim 13 recites an antibody comprising “amino acids of one or more complementarity determining regions (CDRs) selected from the group consisting of a light chain region 1 comprising amino acids 24-35 of SEQ ID NO: 2, a light chain region 2 comprising amino acids 50-56 of SEQ ID NO: 2, a light chain region 3 comprising amino acids 90-98 of SEQ ID NO: 2, a heavy chain region 1 comprising amino acids 30-35 of SEQ ID NO: 1, a heavy chain region 2 comprising amino acids 50-69 of SEQ ID NO: 1, and a heavy chain region 3 comprising amino acids 99-108 of SEQ ID NO: 1. or the antigen binding fragment thereof comprises amino acids of one or more complementarity determining regions (CDRs) selected from the group consisting of a light chain region 1 comprising amino acids 24-34 of SEQ ID NO: 4, a light chain region 2 comprising amino acids 50-56 of SEQ ID NO: 4, a light chain region 3 comprising amino acids 89-97 of SEQ ID NO: 4, a heavy chain region 1 comprising amino acids 30-35 of SEQ ID NO: 3,a heavy chain region 2 comprising amino acids 50-69 of SEQ ID NO: 3, and a heavy chain region 3 comprising amino acids 99-107 of SEQ ID NO: 3.” The broadest reasonable interpretation of the claim is that the antibody may must comprise the individual amino acids (i.e., the amino acids to not have to be in the same order as they are in the instant sequence and they do not have to be adjacent to one another) of only one of the recited CDR regions.
Claim 15 recites, “the antibody or an antigen binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and/or SEQ ID NO: 2; or the heavy chain of the antibody or antigen binding fragment thereof comprises SEQ ID NO: 1 and/or the light chain of the antibody or antigen binding fragment thereof comprises SEQ ID NO: 2, or wherein the antibody or an antigen binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 3 and/or SEQ ID NO: 4 or the heavy chain of the antibody or antigen binding fragment thereof comprises SEQ ID NO: 3 and/or the light chain of the antibody or antigen binding fragment thereof comprises SEQ ID NO: 4.” However, this limitation only requires a heavy chain or light chain with as little as 90% sequence identity to the recited sequences (i.e., the sequence has to contain the individual amino acids of one of the CDRs recited in claim 13, but the CDR regions of the antibody sequence are not required to be identical to any of the recited CDRs).
The claims seek to limit the structure of the antibody by describing the antigen to which the antibody binds, S. aureus Enterotoxin A. However, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011) (patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). See also MPEP 2163.II.A.3(a).
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin.
It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. MacCallum et al. (1996; PTO-892) analyzed many different antibodies for interactions with antigen and state that while no single residue is in contact with the antigen in all structures and CDR3 of the heavy and light chain dominate (pg. 733, paragraph bridging columns), contacts are more common at CDR residues which are located centrally within the combining site and non-contacting residues within the CDRs are important in defining "canonical" conformations (Abstract.). Pascalis et al. (2002; PTO-892) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (2003; PTO-892) which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (Abstract). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.). Vajdos et al. (2002; PTO-892) additionally state that antigen binding is primarily mediated by the CDRs and that the more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations although in some cases framework residues also contact the antigen (page 416, left col.).
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. Rudikoff et al. (1982; PTO-892) teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract). Thus, the art demonstrates that the antibody structure correlated with its antigen-binding function is six CDRs, the sequence of each CDR, and the position of each CDR. In order to demonstrate possession of the antibody or antigen binding fragment thereof capable of binding S. aureus Enterotoxin A as claimed in claims 13, 15, 19, 25, and 37, one must describe a sufficient variety of species of antibody.
MPEP 2163(II)(A)(3)(a)(ii) states (emphasis added):
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 (see i)(A) above), reduction to drawings (see i)(B) above), 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 the inventor was in possession of the claimed genus (see i)(C) above)….
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.
In contrast to the broad genus of antibodies claimed, the instant application described only two antibodies capable of binding S. aureus Enterotoxin A (SEA), anti-SEA 55 and anti-SEA 90 (pg. 30, line 32 – pg. 31, line 8). The specification teaches that anti-SEA 55 has a heavy chain sequence of SEQ ID NO: 1 and a light chain sequence of SEQ ID NO: 2 and that anti-SEA 90 has a heavy chain sequence of SEQ ID NO: 3 and a light chain sequence of SEQ ID NO: 4 (FIGs. 2-3). The specification does not teach antibodies comprising the amino acids of any one of the CDRs, but not comprising the complete, sequential sequence of any of the CDRs, that are capable of binding S. aureus Enterotoxin A.
The art at the time of filing does not remedy this deficiency because while antibodies comprising only one of the complete recited CDRs are known in the art, they are not known to bind S. aureus Enterotoxin A. For example, US 11,203,635 B2 teaches an antibody that binds p53 and has a heavy chain (SEQ ID NO: 6) that contains a sequence identical to the sequence at position 50-69 of instant SED ID NO: 3 (see Figure 1 below for alignment). Additionally, US 2021/0015870 A1 teaches an antibody that binds human BMCA and has a light chain (SEQ ID NO: 7) that is identical to instant SEQ ID NO: 4 (see Figure 2 below for alignment). Thus, the art demonstrates that the presence of one of the recited CDRs or a single heavy or light chain identical to that of the anti-SEA 55 or 90 antibodies is not sufficient to demonstrate a correlation between those structures and the function of binding S. aureus Enterotoxin A.
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Figure 1: Alignment of instant SEQ ID NO: 3 (Qy) with heavy chain of antibody from US 11,203,635 B2 (Db).
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Figure 2: Alignment of instant SEQ ID NO: 4 (Qy) with the light chain of the antibody taught by US 2021/0015870 A1 (Db).
Therefore, claims 13, 15, 19, 25, and 37 are rejected for failing to provide written description of the antibody structures because they fail to demonstrate possession of a representative number of species within the claimed genus.
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 25 and 37 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 25 (upon which claim 37 depends) recites “determining the presence, absence or level of Staphylococcus aureus Enterotoxin A in the sample.” The broadest reasonable interpretation of the term “determining” encompasses mental processes, such as observation and evaluation (see MPEP 2106.04(a)), as is evidenced by an example in the instant specification, which states, “In one embodiment of the present invention the method comprises addition of a sample to a container (such as a well, tube or vial), chip or plate comprising at least the two antibodies of antigen binding fragments (i.e. allowing a first recombinant antibody or antigen binding fragment thereof and a second recombinant antibody or antigen binding fragment thereof to contact with a sample), and measuring or detecting FRET (i.e. thereby determining the presence, absence or level of the target molecule in the sample).” (pg. 11) Based on this example, the step of “determining the presence, absence, or level of Staphylococcus aureus Enterotoxin A in the sample” encompasses observing and evaluating measurements taken after contacting the sample with the antibody. Thus, the full scope of “determining” encompasses mental processes.
This judicial exception is not integrated into a practical application because the application or use of the judicial exception does not go beyond generally linking the use of the judicial exception (i.e., “determining” the presence, absence, or levels of S. aureus Enterotoxin A) to a particular technological environment or field of use. In this case, the recited step of “allowing a recombinant antibody or antigen binding fragment of claim 13 to contact with a sample” is performed in order to gather data for the step of “determining” and is a necessary precursor for all uses of this step. Thus, the preceding step is extra-solution activity, and does not integrate the judicial exception into a practical application. See MPEP 2106.04(d)(2). An example of data gathering that the courts have found to be insignificant extra-solution activity include determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968, as well as performing clinical tests on individuals to obtain input for an equation (In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989)). See MPEP 2106.05(g). See MPEP 2016.05(h). Furthermore, the judicial exception is not integrated into a practical application because the claim does not recite additional elements that apply or use the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition.
Claim 37 (which depends upon claim 25) recites, “wherein the sample is a biological sample, environmental sample, process sample, (raw) material sample, food sample, sample of a food process, dairy product sample, sample of a biochemical agent, swab, or a sample of a subject.” This judicial exception is not integrated into a practical application because claim 37 merely limits an element of the extra-solution activity (i.e., the sample used to gather data). Thus, the limitation does not integrate the judicial exception into a practical application because the application or use of the judicial exception does not go beyond generally linking the use of the judicial exception to a field of use.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional step of allowing a recombinant antibody or antigen binding fragment of claim 13 to contact with a sample is extra-solution activity of preparing for the step of “determining”, as discussed above. Additionally, the additional step only generally links the judicial exception to a particular field of use for the reasons described above. See MPEP 2106.05.
Regarding claim 37, this claim limits the additional step of claim 25 that is extra-solution activity, as described above. Thus, clam 37 does not include additional element that are sufficient to amount to significantly more than the judicial exception.
Therefore, claims 25 and 37 do not qualify as eligible subject matter (see MPEP 2106).
Claim Rejections - 35 USC § 102
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.
Claims 13, 25, and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ji et al. (2019, CN 110526967A; herein “Ji”; citations refer to machine translation attached with this Action).
Regarding claim 13, Ji teaches a nanobody capable of binding Staphylococcus aureus enterotoxin A, which has the amino acid sequence (SEQ ID NO: 1; para. 18): ESGGGSVQAGGSLRLSCAASGDAYMCKCMGWFRQGPGKEREKVAAIYITDGSTYYADSVKGRFTLSQDNAKNTVYLQMNSLKPEDTAMYYCAASTFYGCETGLHGYNYWGQGTQVTVS. This sequence contains all of the amino acids in positions 30-35 of instant SEQ ID NO: 1 (i.e., SSHWIE; these amino acids are underlined in Ji’s SEQ ID NO: 1 above).
Regarding claims 25 and 37, Ji teaches a method for determining S. aureus Enterotoxin A in a sample comprising allowing the nanobody to contact 3% skim milk (i.e., a dairy product sample) and determining the presence, absence, or level of S. aureus Enterotoxin A by adding horseradish peroxidase (HRP)-labeled antibody and measuring the colorimetric change (para. 105).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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