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 .
DETAILED ACTION
Claim Status
The amendment on December 17, 2025 is acknowledged. Claims 1-11 are currently pending. There are no new claims and claims 12-20 are withdrawn. Claims 1-11 will be examined on the merits herein.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11 in reply filed on December 17, 2025 is acknowledged. Claims 12-20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
The application 18/522,221 filed on November 29, 2023 claims priority from the provisional application 63/385,395 filed on November 29, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 13, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim 4 contains the trademark/trade name nanobody. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe single-domain antibodies derived from camelid heavy-chain-only antibodies and, accordingly, the identification/description is indefinite.
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.
Claims 1, 3-4 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (US 20090163379 A1; hereafter Wang; PTO-892) in view of Yu et al. (US 20210198806 A1; hereafter Yu; PTO-892).
Wang teaches a yeast expression display of protein products encoded by a diverse repertoire of coding sequences on the surface of yeast cells by displaying recombinant proteins in the periplasmic space of yeast cells, recombinant proteins linked to a cell membrane-spanning transmembrane domain, a cell-membrane associated protein domain that is on the external face of the yeast cell membrane, a protein that binds to the inner face of the yeast cell wall, or a periplasmic protein in order to display proteins in the yeast periplasmic space. Wang teaches signal sequence that directs transport of the fusion protein to the yeast host cell periplasm, plasma membrane, or cell wall such that the fused protein variant is displayed in the periplasm. See embodiments [0111]. Wang explicitly teaches displayed library members anchored to the cell wall as a consequence of being directly fused to a coding sequence that encodes a cell wall outer membrane protein which is pertinent to claims 1.
Wang also teaches the yeast, Saccharomyces cerevisiae and display of a genetically diverse repertoire or library of polypeptides on the surface of yeast cells, e.g. antibody libraries, which is pertinent to claim 3 and 4. See for example abstract and embodiments [0003], [0005], [0007], [0009] and [0012].
Wang teaches the inducible promoter and proteins on the outer membrane of yeast cells after galactose induction detected by a green, red or yellow fluorescent signal, which is pertinent to claims 1, 9-11. See for example embodiments [0022, 0023, 0027, 0096, 0098].
However, Wang does not explicitly teach an inducible reporter dependent on activation of a receptor and the fluorescent protein, mTurgoise2 (claims 1, 9-11).
Yu teaches a yeast periplasmic display library comprising a reporter system wherein a reporter gene operably linked to an inducible promoter is activated when the target membrane protein of interest is activated to allow detection of increases or decreases in activity of the target membrane protein of interest upon binding of the antibody to the target membrane protein of interest, which is pertinent to claim 1 and 11. See for example claims 14, 18 and embodiments [0020, 0026, 0147, 0150]. Yu also teaches Saccharomyces cerevisiae and the genetically encoded ligands, antibody mimetics, aptamers, antigens, enzymes, receptors and cyan fluorescent protein which is pertinent to claims 3-4 and 9-10. See for example claims 78-79, 85 and embodiments [0005, 0008, 0017, 0026, 0080, 0107-0110].
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang by selecting the inducible reporter system and the cyan fluorescent protein disclosed in the yeast periplasmic display of Yu, thereby arriving at the invention of claims 1, 3-4, 9-11. Since the inducible reporter system of Yu and the yeast anchored to the cell wall expression display of Wang were both shown to be effective in display proteins in the yeast periplasmic space, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
Claim 2 is rejected as unpatentable under 103 over Wang et al. (US 20090163379 A1; hereafter Wang; PTO-892) in view of Yu et al. (US 20210198806 A1; hereafter Yu; PTO-892) as to applied to claims 1, 3-4, 9-11 above, and further in view of Tanaka et al. (Published January 14, 2015; hereafter Tanaka; PTO-892).
The reasons why claims 1, 3-4, 9-11 would have been obvious over Wang in view of Yu are set forth above.
However, neither reference explicitly teaches the cell-wall anchoring protein comprises an N-terminus projected in the periplasmic space, and wherein the ligand is fused to the N-terminus of the cell-wall anchoring protein as in claim 2.
Tanaka teaches N- and C-terminus fused anchor proteins for cell-surface display depends on its application. Tanaka also teaches that for N-terminal fusions, the N-terminus of the anchor protein is genetically fused to the C-terminus of the target protein. A signal sequence for secretion is also fused to the N-terminus of the target protein to facilitate transport to the cell surface.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang and Yu by using Tanaka’s teachings, thereby arriving at the invention of claim 2. Since Wang and Yu’s yeast periplasmic ligand display were both shown to be effective in display ligand proteins fused to anchoring cell proteins in the yeast periplasmic space, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (US 20090163379 A1; hereafter Wang; PTO-892) in view of Yu et al. (US 20210198806 A1; hereafter Yu; PTO-892), as applied to 1,3-4 and 9-11 and further in view of Fowlkes et al. (US6100042-A; hereafter Fowlkes; PTO-892).
The reasons why claims 1, 3-4 and 9-11 would have been obvious over Wang in view of Yu are set forth above. However, neither reference teaches the signal sequence, SEQ ID NO: 21
Fowlkes teaches the ammino acid sequence of different regions of MF.alpha.1, including the promoter, transcription terminator, and different domains of the precursor protein: the signal peptide, the pro peptide, the four repeats of mature .alpha.-factor, and the three spacers which separate these repeats cloned into the pALTER plasmid. Fowlkes teaches the use of the MF.alpha.1 sequences to secrete a peptide library into the yeast periplasm, which is pertinent to claims 5-6. See Fowlkes et al. example 3; Figure 2; page 95.
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It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang and Yu by using Fowlkes teachings, thereby arriving at the invention of claims 5-6. Since Wang and Yu’s yeast periplasmic ligand display were both shown to be effective in using different types of signal sequences to direct transport the fusion protein to the yeast cell periplasm, plasma membrane or cell wall such that the fused protein is displayed for example in the periplasm, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable Wang et al. (US 20090163379 A1; hereafter Wang; PTO-892) in view of in view of Yu et al. (US 20210198806 A1; hereafter Yu; PTO-892) as applied to 1,3-4 and 9-11 and further in view of Moukadiri et al. (Published April, 1997; hereafter Moukadiri; PTO-892).
The reasons why claims 1, 3-4 and 9-11 would have been obvious over Wang in view of Yu are set forth above.
Wang teaches the yeast cell wall anchoring protein, ICWP and its use for displaying peptides and proteins in Saccharomyces cerevisae, which is pertinent to claims 7-8.
However, Wang does not teach SEQ ID NO:13 as in claims 7-8.
Moukadiri teaches ICWP (EMBL accession number YLR391w, frame +3) amino acid sequence and its localization in the cell wall of Saccharomyces cerevisae, which is pertinent to claims 7-8. See Figure below.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang and Yu by using Moukadiri teachings, thereby arriving at the invention of claims 7-8. Since Wang and Yu’s yeast periplasmic ligand display were both shown to be effective in display ligand proteins fused to anchoring cell proteins in the yeast periplasmic space. Also, since specifically Wang’s teachings on using the cell wall anchoring protein, ICPW (CCW14) fused to target ligand proteins has been showed to be efficient for displaying proteins on the cell surface of S. cerevisae, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., signal sequences, yeast cell wall anchoring proteins, ligands fused to the yeast cell wall display and ligands secreted to periplasmic space) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571) 272-2784. The examiner can normally be reached M-F 6:15AM-3:15PM.
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/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645