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 .
Priority
This application is a 371 of PCT/EP2022/052193, filed on 01/31/2022, and claims foreign priority to EP21154190.9. Applicant has claimed the filing date of 01/29/2021 based on EP21154190.9 but no certified copy or translation has been made of record.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/26/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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).
The specification filed on 02/06/2024 does not recite appropriate sequence identifiers in the form of SEQ ID numbers. For example, please see: [0029] page 7, [0040] page 9, [0128] page 34. The sequences recited in the specification must include SEQ ID numbers to properly identify the sequences. Appropriate correction is required.
The claims filed on 02/06/2024 do not recite appropriate sequence identifiers in the form of SEQ ID numbers. The sequences recited in the claims must include SEQ ID numbers to properly identify the sequences. For example, an appropriate form of the sequence “ERNNF” of claim 26 is “ERNNF” (SED ID NO: 1)”. Appropriate correction is required.
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.
Claim Objections
Claim 26 is objected to for failing the comply with 37 CFR 1.821 (d) which requires reference made to an unbranched sequence of four or more amino acids by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description of claims, even if the sequence is also embedded in the text of the description or claims of the patent application. See MPEP §2422.
Claim Rejections - 35 USC § 112
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 16-35 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “% sequence homology” in claims 16 and 27 are
presumably used by the claim to mean either “sequence similarity”, or “sequence identity”, while the
accepted meaning is that “homology” is distinct from “sequence similarity” or “sequence identity”, and
that references to “% homology” are not scientifically meaningful as explained below. The term is
indefinite because the specification does not clearly redefine the term. Specifically, the prior art teaches
that references to percent homology do not have a set meaning. For example, the prior art of Koonin et
al. (Chapter 2 Evolutionary Concept in Genetics and Genomics, Sequence - Evolution - Function: Computational Approaches in Comparative Genomics. Boston: Kluwer Academic; 2003; NCBI Bookshelf;
attached as pdf, 25 pages; hereafter “Koonin”) notes that “homology” implies a common evolutionary origin (see, e.g., Koonin at § 2.1.1 at page 1), and further states that -a conclusion that two (or more) genes or proteins are homologous is a conjecture, not an experimental fact. We would be able to know for a fact that genes are homologous only if we could directly explore their common ancestor and all intermediate forms. Even when one comes up with a figure—say, two protein sequences have 10% identical residues and additional 8% similar amino acid residues (a total of 18% similarity)—does this imply homology or not? The only reasonable answer is: it depends. An alignment of non-homologous sequences is inherently meaningless and potentially misleading. Even if such an alignment attains a relatively high percentage of identity or similarity, no conclusions at all can be inferred from the correspondence between aligned residues. This is why phrases like “significant homology” or “percent homology” are ludicrous. Homology is a qualitative notion of common ancestry. As long as homology is established, 10% identical residues between two protein sequences could be highly meaningful and amenable to functional interpretation. In contrast, even 30% identity between two sequences that are not homologous in reality could be totally misleading (see, e.g., Koonin at § 2.1.1 at pages 1-3). Notably, Koonin opines that “the term ‘homology’ is used basically as a glorified substitute for
‘sequence (or structural) similarity’ (see, e.g., Koonin at § 2.1.1 at pages 1 at 3rd full ¶).
However, although Webber et al. (Genes and homology, Current Biology, vol. 14(9):R:332-R333
(May 4, 2004); hereafter “Webber”) agrees with Koonin that sequence similarity is “[d]efinitely not” the
same as sequence homology (see, e.g., Webber at R332 at col II-III at bridging ¶), Webber opines that
research papers sometimes wrongly quote values of ‘percent homology’. In these cases, ‘percent
identity’ is meant, as two genes either have a common ancestor or they do not (see, e.g., Webber at
R332 at col II-III at bridging ¶).
Therefore, although Koonin and Webber both agree that “sequence homology” is not the same
as sequence identity or sequence similarity, both documents make different presumptions about the
presumed meaning implied by researchers (i.e., whether or not the term should imply “sequence similarity” or “sequence identity”) (see, e.g., Koonin at § 2.1.1 at pages 1 at 3rd full ¶; see also Webber at R332 at col II-III at bridging ¶). This difference in preferred interpretation between Koonin and Webber is informative of the overall confusing nature of references to “% homology” or “% homologous” because “sequence similarity” and “sequence identity” are not equivalent or synonymous terms as explained by the prior art of Rost (see, e.g., Rost, Twilight zone of protein sequence alignments, Protein Engineering, vol. 12(2):85-94 (1999)). Rost identifies that proteins can be 100% homologous while sharing less than 10% sequence identity (see, e.g., Rost at 85 at col I-II at bridging ¶; see also id. at
abs). Rost specifically identifies that the terms “sequence identity”, “sequence similarity”, and
“sequence homology” are not synonymous and have distinct, art-recognized definitions (see, e.g., Rost
at 85 at col II at 1st full ¶, defining sequence identity; Rost at 86 at col II at § “Definition of sequence
identity and sequence similarity”; Rost at 85 at abs, col I at § Introduction, identifying homology is not
equivalent to identity). Therefore, it is clear in the art that “% sequence homology” as recited at instant claim 16 and 27 is a misused and confusing term in the art that is not synonymous nor equivalent in scope to either “sequence identity” or “sequence similarity”; this is because “homologous” only implies the existence of a common evolutionary ancestor. Therefore, in the complete absence of a definition, it is unclear if Applicant meant “% homologous” to imply:
(a) percent “sequence identity”;
(b) percent “sequence similarity”;
(c) the existence of homology (i.e., a common ancestor); or
(d) something else entirely.
The correct interpretation substantially and materially alters the pending claim scope because
two sequences may share 95% sequence similarity but share 0% sequence identity, and still presumably
be homologous. However, two sequences may share 35% sequence identity but not be homologous at
all. Per MPEP § 2173.02(II), if the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a
rejection of the claim under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, is
appropriate. Accordingly, because the correct interpretation of “% sequence homology” as recited at claims 16 and 27 materially and substantially alters the scope of the pending claims, the term is not clearly and unambiguously defined on record or in the prior art. Therefore, claims 16 and 27 are indefinite.
Claim 17-26 and 28-35 which depends on claim 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112(pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 16.
Allowable Subject Matter
SEQ ID NO: 9 and SEQ ID NO: 8 are free of the prior art.
The following is a statement of reasons for the indication of allowable subject matter in claims 16-35: SEQ ID NO: 9 is free of the prior art. The closest prior art reference WO2010/080819A1 (reference provided in the IDS) teaches the sequence; SEQ ID NO: 2325 (see page 237), which has 96% sequence identity to SEQ ID NO: 9. The reference provides no teaching, suggestion or motivation for glutamic acid or glutamine residues at the variable X1, X2 or X3 positions in SEQ ID NO: 9. As noted, the reference does not encompass the limitations of claim 1. SEQ ID NO: 8 is free of the prior art. The closest reference WO2010/080819A1 teaches linkers (see Table 16, page 295) and SEQ ID NO: 2325 which has 72% sequence identity to SEQ ID NO: 8 but there is no teaching suggestion or motivation to make SEQ ID NO: 8.
Therefore, SEQ ID NO: 9 and SEQ ID NO: 8 are novel and non-obvious.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654