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 .
2. Claims 12-14, 23-24 and newly added claims 27-31 are pending.
3. Newly added claims 27-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/07/2023.
4. Claims 12-14 and 23-24 are under consideration as they read on contacting the antigen of SEQ ID NOs:2, 13 or 47 with a sample comprising an antibody to detect antibodies in the sample which bind to the antigen.
5. The following rejection is maintained in view of Applicant’s amendment filed on 12/19/2025.
6. 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.
7. Claims 12-14 and 23-24 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.
Claims 12-14 and 23-24 are unclear and indefinite.
The recitation of “a polypeptide comprising at least one epitope, wherein the epitope is an amino acid sequence selected from the group consisting of SEQ ID NOs: 296-303, 527, 528, 531,535-537, 540-542 and 544-552, and wherein said polypeptide has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST, wherein (i) the polypeptide has a molecular weight of 20 to 50 kDa or (ii) the number of amino acid residues of the polypeptide is 500 or less” in claim 12 makes no sense.
SEQ ID NO:2 is 277 amino acids;
SEQ ID NO:47 is 341 amino acids; and
SEQ ID NO:13 is 438 amino acids.
There are no polypeptides which have 90% at least sequence identity to the amino acid sequence of SEQ ID NO:2, 13 or 47 which are 20kDa. Even 90% sequence identical true fragments, (which are the smallest polypeptides encompassed) of SEQ ID NOs 2, 47 and 13 are 249 amino acids, 306 amino acids and 394 amino acids in length and none of them can possibly be 20 kDa. In fact, the very lowest it could be is around 27 kDa for a 90% identical fragment of SEQ ID NO:2.
There are no polypeptides which have 90% at least sequence identity to the amino acid sequence of SEQ ID NO:2 which are less than 249 amino acids in length.
There are no polypeptides which have 90% at least sequence identity to the amino acid sequence of SEQ ID NO:47 which are less than 306 amino acids in length.
There are no polypeptides which have 90% at least sequence identity to the amino acid sequence of SEQ ID NO:13 which are less than 394 amino acids in length.
Correction is required.
Applicant’s argument filed on 12/19/2025 have been fully considered, but are not found persuasive.
“To further clarify the claims, claim 12 has been amended to recite "wherein the polypeptide's total length has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST."
As one of skill in the art would appreciate, BLAST is an often-used local sequence alignment program designed to find regions of similarity (such as motifs or domains), by identifying matching short stretches of sequence "words" and then extending them to longer alignment. As a result, BLAST is ideal for aligning distant relatives or finding conserved regions in otherwise dissimilar sequences.
On the other hand, global sequence alignment programs, such as those based on the Needleman-Wunsch principle, align entire sequences end-to-end, often forcing matches and inserting gaps to achieve end-to-end alignment between even dissimilar sequences. Such global sequence alignment tools are best for aligning closely related sequences with high overall similarity and are best for revealing overall evolutionary relationships. But such alignments can be misled by large insertions/deletions introduced by the program.
The Examiner seems to be misinterpreting the claims - which explicitly requires using local alignment using BLAST - to mean using a global alignment tool not named in the claims.
Specifically, the Examiner appears to have read the "at least 90% sequence identity" limitation only within the context of "at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47", thereby interpreting that the claims require the polypeptide to have at least 90% of the amino acid sequence of SEQ ID NO: 2, 13 or 47. However, Applicant respectfully points out that previously presented claim 12 recites "wherein said polypeptide has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST."
As mentioned above, BLAST is a well-known and widely use local sequence alignment tool. When the Examiner fully considers the limitation that the sequence identity is in accordance with how it is defined by BLAST, the "at least 90% sequence identity... based on percent identity determined using BLAST" do not conflict with the limitations "(i) the polypeptide has a molecular weight of 20 to 50 kDa or (ii) the number of amino acid residues of the polypeptide is 500 or less".
It appears that Applicant has once addressed the meaning of "sequence identity" in the Response to Final Office submitted on August 7, 2024, which explains that the percentage of "sequence identity" according to BLAST is not determined over the whole length of the subject sequence (i.e., the full length of SEQ ID NO: 2, 13, or 47), but is rather the percentage identity over the locally optimal aligned segment.
Multiple resources concerning BLAST provides that the "identity" determined by BLAST is "the highest percent identity for a set of aligned segments to the same subject sequence" (e.g., Uniformed Services University's "Introduction to NCBI Bioinformatics Resources: BLAST Results"at ht ; UC Berkeley
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Library's introduction toBLAST at t.!uid&ibix,kc;c/ncbi/b>.). Applicant submits herewith a printout of the Uniformed Services University's page on "BLAST results"; the definition for "identity" may be found at page 3 of the document.
To further demonstrate, Applicant shows below the BLAST result of the alignment of SEQ ID NO: 296 (SPRTCDVVLKLPELT) to SEQ ID NO: 47 as an example. In paragraph [0059], the specification teaches that SEQ ID NO: 296 is the 15-amino-acid epitope spanning amino acids 14-28 of SEQ ID NO: 47 (which has 341 amino acid total). Applicant used Protein BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi), entering SEQ ID NO: 296 as the "query sequence" and SEQ ID NO: 47 as the "subject sequence". It can be been seen from this result that the subject sequence length is 341 amino acids the length of SEQ ID NO: 47), but the sequence identity was determined to be 100%, because it is defined as percentage of identity over the aligned segment which spans 15 amino acids:
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:Query_12745Lenth341NumberofMatches3
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Therefore, Applicant respectfully requests that the Examiner views the claim according to how the terms are understood in the field of the claimed invention.
For the reasons stated above, Applicant submits that the limitations "the polypeptide has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST" and "wherein (i) the polypeptide has a molecular weight of 20 to 50 kDa or (ii) the number of amino acid residues of the polypeptide is 500 or less" are clear and definite.
Accordingly, reconsideration and withdrawal of this rejection are respectfully requested.
Contrary to Applicant’s assertion, the term “at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST” does not mean what Applicant argues. At the outset “sequence identity to the amino acid sequence of SEQ ID NO: 2, 13 or 47 based on percent identity determined using BLAST” is unclear and indefinite. What does sequence identity “based upon percent identity determined by BLAST” even mean? How is it “based upon” that? Sequence identity, including as defined on the BLAST website is “The extent to which two (nucleotide or amino acid) sequences have the same residues at the same positions in an alignment, often expressed as a percentage. The claim language recites that the sequence has at least 90% sequence identity to SEQ ID NOs 2, 13 or 47. To find sequences which fall within that parameter one searches SEQ ID NOs 2, 13 and 47. One does not start from a search of each sequence to see which ones bring up SEQ ID NOs 2, 13 or 47 with 90% or more sequence identity.
90% sequence identical sequences to SEQ ID NOs 2, 13 and 47 is a limitation and the issues remain as the Examiner argues supra with respect to length and molecular weight. The USPTO sequence searching by STIC is what will be used for any recitations of sequences within the claims and percent identity to particular sequences. There is no way to even perform the search that Applicant argues that the claims read upon for a single sequence much less all of the sequences recited.
Correction is required.
8. No claim is allowed.
9. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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April 1, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights