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 without traverse of Group III in the reply filed on 05/29/2026 is acknowledged.
Species Election: Applicant has elected the following species:
VL is fused to an immunoglobulin light chain constant domain and the VH is fused to an immunoglobulin heavy chain constant domain having an Fc domain (as recited in claim 44); and
Surface anchor polypeptide which comprises between 400 to 700 amino acids (as recited in claim 87).
Claims 24, 28, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 44 and 85-100 are directed to the elected invention and have been examined on their merits.
Priority
The present application is a § 371 National Stage Entry of PCT/US2021/059814 (filed on 11/18/2021) which claims benefit of U.S. provisional application 63/117,289 (filed on 11/23/2020).
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/26/2023 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
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/patents-application- process/filing-online/legal-framework-efs-web), 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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item (1)(a)(iii) above. Specifically, the incorporation by reference
paragraph recites the size of the sequence listing in kilobytes. Compliant sequence listing file sizes must be presented in bytes, rather than kilobytes.
Required response - Amendment of the specification to recite the size of the sequence listing file in bytes rather than kilobytes.
Claim Objections
Claim 44 is objected to because a colon should be added after “comprising” in line 1.
Claim 86 is objected to because although it is apparent that “the numbering” is directed to “N297”, the claim should be amended to refer to “N297” not “the numbering” because the claim does not establish a “numbering”. Alternatively, applicant may simply delete “wherein the numbering is in accordance with the Eu numbering scheme”.
Claim 100 is objected to because a colon should be added after “expresses” in line 2.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112:
(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.
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 89 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 89 is rejected as being indefinite because it recites the approximation “about”.
MPEP § 2173.05(b)(III)(A)
In determining the range encompassed by the term "about," one must consider the context of the term as it is used in the specification and claims of the application.
Applicant’s disclosure has been fully considered but there is no guidance which would apprise a person having ordinary skill in the art as to what is meant by “about 401, 430, or 481 amino acids”. For example, does applicant considered 375 to be “about 401”? Or is there some other definite variation from the recited amino acid lengths which is encompassed by “about”?
For at least these reasons, the metes and bounds of claim 89 are not distinctly defined.
For the purpose of examination, this claim has been examined for the values recited in the claim because it is not possible to determine whether a protein is a protein having “about” the recited number of amino acids.
Claim 95 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 95 depends from claim 94 and requires the chimeric surface anchor polypeptide to comprise the amino acid sequence set forth in SEQ ID NO: 34 or SEQ ID NO: 35.
Claim 94 requires that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
SEQ ID NO: 34 is described by applicant as being a SED1-FLO5 fusion protein anchor (Specification, p. 16, lines 28-34; Sequence Listing).
Therefore, this claim does not properly depend because it broadens the scope of claim 94 to include FLO5 cell wall proteins which are not included in the list recited in claim 94.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 44, 85, 87, 91, and 99-100 are rejected under 35 U.S.C. 103 as being unpatentable over Zha et al. (US 2016/0355569 A1) in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
Regarding claims 44 and 87, Zha teaches an antibody display system comprising:
an isolated eukaryotic host cell (e.g., Pichia pastoris or Saccharomyces cerevisiae; a yeast cell; [0038]);
a bait comprising a Fc immunoglobulin domain or functional fragment thereof fused to a surface anchor polypeptide or functional fragment thereof;
one or more polynucleotides encoding an immunoglobulin light chain variable region; and
one or more polynucleotides encoding an immunoglobulin heavy chain variable region [0009].
In certain embodiments, Zha’s eukaryote comprises “a polynucleotide encoding the bait which is operably associated with a regulatable promotor” (Id.). Zha teaches that the surface anchor peptide can be SED1 or a functional fragment thereof ([0010]-[0016]). More specifically, Zha teaches an example using Saccharomyces cerevisiae SED1 driven by a Pichia pastoris AOX1 promoter ([0020]; Fig. 1). Zha’s SED1 is represented by SEQ ID NO: 2 which is 322 amino acids residues in length (i.e., more than 320 amino acids)([0113])
Zha teaches that a fully antibody comprises a light chain and heavy chain and each chain includes a variable region of about 100 to 110 or more amino acids and a constant domain ([0053]).
Accordingly, with respect to the instant claim, Zha teaches:
A yeast host cell comprising:
a first polynucleotide encoding a bait comprising an immunoglobulin Fc domain fused to a cell surface anchor polypeptide, which said cell surface anchor polypeptide comprises more than 320 amino acids, operably linked to a regulatable promoter;
a second polynucleotide encoding an immunoglobulin light chain (LC) comprising a variable domain (VL) fused to an immunoglobulin light chain constant domain (CL); and
a third polynucleotide encoding an immunoglobulin heavy chain (HC) comprising a variable domain (VH) fused to an immunoglobulin heavy chain constant domain having an Fc domain (CH).
Zha differs in that it does not explicitly teach that the host yeast cell is a diploid yeast cell.
Weaver-Feldhaus et al. teaches that creating reagents which bind with high specificity and affinity to relevant biomolecules is one of the most critical and challenging tasks facing biologists (p. 24, left col., par. 1). Weaver-Feldhaus teaches that library size is the single most important determinant of antibody diversity and affinity but creating such large yeast antibody libraries is quite time and labor intensive (p. 24, right col., par. 2). Because Fabs are composed of two distinct polypeptide chains, it is possible to encode the two chains on different vectors and in different yeast strains and the two chains can then be brought together in a single diploid yeast by mating, which is a highly efficient process (p. 24, right col., par. 2; Fig. 1). To this end, Weaver-Feldhaus reports the construction of yeast vectors and strains for large heterodimeric Fab libraries by maturing Saccharomyces cerevisiae (Id.). Specifically, Weaver-Feldhaus teaches that the library can be used to rapidly construct large Fab libraries from which multiple high affinity Fab can be isolated (Id.).
Therefore, because Zha differs only in that it does not teach a diploid yeast host cell and because Weaver-Feldhaus teaches that yeast antibody libraries can be generated in diploid yeast host cells such as Saccharomyces cerevisiae, it would have been obvious to have modified Zha such that the yeast cell is diploid. There would have been a reasonable expectation of success because Weaver-Feldhaus teaches that diploid antibody expressing yeast cells can be used to rapidly construct large libraries resulting in a system with rapid affinity maturation or humanization and should significantly facilitate the generation of reagent, diagnostic, and therapeutic antibodies (p. 34, left col., par. 3). This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Regarding claim 87, applicant has elected a cell surface anchor polypeptide comprising between 400 to 700 amino acids. Zha teaches a bait comprising the human Fc immunoglobulin domain fused to a SED1 polypeptide (SEQ ID NO: 4) which is 570 amino acids in length (i.e., a cell surface anchor polypeptide comprising between 400 to 700 amino acids).
Thus, claims 44 and 87 are obvious over Zha in view of Weaver-Feldhaus.
Regarding claim 85, as discussed above, Zha in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. Zha teaches that the HCs are classified as gamma, mu, alpha, delta, or epsilon, based on the type of constant domain in the heavy chain, and may be an isotype as IgG such as IgG1 or IgG4 ([0053]). Zha further teaches that the Fc suitable for use in the bait comprises an Fc such as IgG1 or IgG4 ([0010] and [0061]).
Therefore, Zha in view of Weaver-Feldhaus also renders obvious the diploid yeast host cell, wherein the CH is an IgG1 CH and the Fc immunoglobulin domain is an IgG1 Fc immunoglobulin domain or the CH is an IgG4 CH and the Fc immunoglobulin domain is an IgG4 Fc immunoglobulin domain.
Regarding claim 91, as discussed above, Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. Zha also teaches that the polynucleotides may be associated with heterologous sequences ([0035]).
Accordingly, Zha in view of Weaver-Feldhaus also renders obvious the diploid yeast host cell wherein the cell surface anchor polypeptide is a chimeric surface anchor polypeptide comprising a Saccharomyces cerevisiae SED1 protein and a heterologous protein.
Regarding claim 99, as discussed above, both Zha and Weaver-Feldhaus teach Saccharomyces cerevisiae.
Regarding claim 100, as discussed above, Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell. Zha teaches that the host cell expresses the polypeptide fused to the surface or a full antibody ([0056]). Therefore, the system made obvious by Zha in view of Weaver-Feldhaus expresses:
(i) a non-tethered full-length bivalent antibody tetramer comprising two HCs and two LCs; and/or
(ii) a monovalent antibody fragment comprising one HC and one LC complexed with the immunoglobulin Fc domain of the bait (structure discussed in [0053] of Zha).
Claims 44, 85-87, 91, and 99-100 are rejected under 35 U.S.C. 103 as being unpatentable over Zha et al. (US 2016/0355569 A1) in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Wang et al. (Protein & Cell, 2018, Vol. 9(1), pages 63-73).
The teachings of Zha and Weaver-Feldhaus are set forth above and applied herein. Zha and Weaver-Feldhaus are found to render obvious claims 44, 85, 87, 91, and 99-100.
Regarding claim 86, as discussed above, Zha in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44.
The instant claim differs because neither Zha nor Weaver-Feldhaus teach that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Wang teaches that therapeutic monoclonal antibodies are among the most effective biotherapeutics to date and one important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions (abstract). Wang reviews various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype (Id.). Wang teaches that IgGs contain a conserved glycosylation site at amino acid N297 in the CH2 domain (p. 66, right col., par. 3). For cases where mAbs are intended to engage cell surface receptors and prevent receptor-ligand interactions, it may be desirable to reduce or eliminate effector function (p. 68, left col., par. 2). An early approach to reduce effector function was to mutate the glycosylation site at N297 with mutations such as N297A (p. 68, left col., par. 3). Wang teaches that this N297 is with EU numbering (p. 64, left col., par. 1).
Thus, because Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell expressing an Fc domain and CH as well as a bait, it would have been particularly advantageous to have reduced effector function (“for cases where mAbs are intended to engage cell surface receptors”). Accordingly, it would have been obvious to have further modified Zha’s yeast host cell such that the immunoglobulin Fc doman and the CH comprise an N297A amino acid substitution. There would have been a reasonable expectation of success because Wang teaches that N297A substitution is among one of the early Fc engineering methods. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Claims 44, 85, 87-88, 91, and 99-100 are rejected under 35 U.S.C. 103 as being unpatentable over Zha et al. (US 2016/0355569 A1) in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Gnanasundram et al. (Molecular Biology of the Cell, 2014, Vol. 26, pages 762-768).
The teachings of Zha and Weaver-Feldhaus are set forth above and applied herein. Zha and Weaver-Feldhaus are found to render obvious claims 44, 85, 87, 91, 99, 100.
Regarding claim 88, as discussed above, Zha in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. Zha teaches that the host cell comprises a polynucleotide encoding the bait which is operably associated with a regulatable promoter ([0009], [0016], and [0050]).
The instant claim differs because neither Zha nor Weaver-Feldhaus teaches that the regulatable promoter is a TetO7 promoter.
Gnanasundram et al. teaches that protein depletion is a widely used approach for studying functions of essential genes and a protein can be depleted by for example repression of the gene’s promoter, degradation or inhibitions of its mRNA translation, or destabilization and degradation of the protein itself (p. 762, left col., par. 1). Among the repressible promoters taught by Gnanasundram is TetO7 (Id.). Gnanasundram teaches the development of enhanced TetO7 repressible promoters in S. cerevisiae (abstract; p. 767, left col., par. 3) and teaches that its promoters represent a valuable improvement on existing protein depletion systems and greatly reduce the time required for an efficient depletion of a studied target protein (p. 766, right col., par. 2 through p. 767, left col., par. 1). Additionally, the use of TetO7 does not require a change in growth conditions which could affect processes under investigation (p. 767, left col., par. 1).
Thus, because Zha and Weaver-Feldhaus render obvious a bait which is operably associated with a regulatable promoter and because Gnanasundram teaches that in yeast such as S. cerevisiae, TetO7 promoters can be used to rapidly deplete (i.e., operably regulate) expression, it would have been obvious to have further modified Zha such that the regulatable promoter is TetO7. There would have been a reasonable expectation of success because Zha teaches a generic regulatable promoter (i.e., is not limited to a single promoter; [0036]) and because TetO7 was previously known to be useful in yeast such as S. cerevisiae for rapid regulation of protein expression. There is no evidence of record that TetO7 exhibits an unexpected or remarkable result. To the contrary, applicant teaches that the tetracycline regulatable promoter is “well-known in the art” (specification, p. 38, line 33 through p. 39, line 22).
Thus, claim 88 is obvious over Zha in view of Weaver-Feldhaus and Gnanasundram.
Claims 44, 85, 87, 91, 93-94, and 99-100 are rejected under 35 U.S.C. 103 as being unpatentable over Zha et al. (US 2016/0355569 A1) in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Furukawa et al. (Biotechnology Progress, 2006, Vol. 22, pages 994-997).
The teachings of Zha and Weaver-Feldhaus are set forth above and applied herein. Zha and Weaver-Feldhaus are found to render obvious claims 44, 85, 87, 91, and 99-100.
Regarding claims 93-94, as discussed above, Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. Zha also teaches that the polynucleotides may be associated with heterologous sequences ([0035]).
The instant claims differ because neither Zha nor Weaver-Feldhaus teach that the heterologous protein:
(93) is a minisatellite-like repeat sequence from a yeast cell wall protein; or
(94) that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
Furukawa et al. teaches that there have been numerous studies of expression systems for the display of heterologous proteins on the cell surface of microorganisms (such as in combinatorial library construction in S. cerevisiae)(p. 994, left col., par. 1). And to display proteins on the cell surface of S. cerevisiae, native cell wall proteins such as α-agglutinin and Flo1 with a serine/thereonine rich hydrophobic tail for glycosylation and a glycosylphosphatidylinositol (GPI) anchor attachment signal at the C-terminus have been used (Id.).
Thus, because Zha in view of Weaver-Feldhaus renders obvious a surface display system comprising a diploid yeast host cell and a bait comprising SED1, it would have been obvious to have further modified the system such that the polynucleotide is also associated with a heterologous sequence such as FLO1. There would have been a reasonable expectation of success because Furukawa demonstrates this protein as being useful in protein presentation systems, particularly in the “extensively studied” S. cerevisiae for library construction. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claims 93-94 are obvious over Zha in view of Weaver-Feldhaus and Furukawa.
Claims 44, 85, 87, 91, 97-100 are rejected under 35 U.S.C. 103 as being unpatentable over Zha et al. (US 2016/0355569 A1) in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and de Ruijter et al. (Microbial Cell Factories, 2016, Vol. 15(87), pages 1-18).
The teachings of Zha and Weaver-Feldhaus are set forth above and applied herein. Zha and Weaver-Feldhaus are found to render obvious claims 44, 85, 87, 91, and 99-100.
Regarding claims 97-98, as discussed above, Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. Zha also teaches that the polynucleotides may be associated with heterologous sequences including promoters ([0035]).
However, neither Zha nor Weaver-Feldhaus teach:
(97) that the second and third polynucleotides are each operably linked to a second regulatable promoter; or
(98) that the second regulatable promoter is a GAL1 promoter.
de Ruijter teaches an S. cerevisiae “IgG factory” (p. 4, right col., par. 1). Specifically, de Ruijiter provides a system harboring a plasmid for IgG gene integration wherein the plasmid contained genes for heavy and light chains each under GAL1-promoter (p. 14, left col., par. 2).
Accordingly, because Zha in view of Weaver-Feldhaus renders obvious a diploid yeast host cell system comprising polynucleotides which are associated with heterologous sequences and because de Ruijter teaches the creation of plasmids harboring GAL1-promoters associated with light and heavy chains (corresponding to the second and third polynucleotides), it would have been obvious to have modified Zha in the same way in order to arrive at a diploid yeast host cell wherein the second and third polynucleotides are each operably linked to a second regulatable promoter such as GAL1. There would have been a reasonable expectation of success because de Ruijter teaches the existence of such systems and teaches that such systems are suitable to regulate IgG expression (Fig. 6). This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claims 97-98 are obvious over Zha in view of Weaver-Feldhaus and de Ruijter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 44, 85, 87, 91, and 99-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,365,846 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
The ‘846 patent is directed to:
An antibody display system comprising an isolated host cell (claims 1-3 and 13-40);
A method for determining if an antibody specifically binds to an antigen (claims 4-8);
A method for making an antibody display system (claim 9);
A method for making an antibody (claims 10-11); and
A method for determining the effect of a sugar on an antibody (claim 12).
Regarding claim 44, ‘846 teaches an antibody display system comprising an isolated host cell such as Pichia or S. cerevisiae (i.e., a yeast host cell). ‘846 also teaches a polynucleotide encoding a bait comprising a heavy Fc immunoglobulin domain fused to a surface anchor polypeptide operably associated with a regulatable promoter;
one or more polynucleotides encoding an immunoglobulin light chain variable region; and
one or more polynucleotides encoding an immunoglobulin heavy chain variable region.
Accordingly, the claims differ in that ‘846 does not specify the ploidy of the yeast cell.
Weaver-Feldhaus et al. teaches that creating reagents which bind with high specificity and affinity to relevant biomolecules is one of the most critical and challenging tasks facing biologists (p. 24, left col., par. 1). Weaver-Feldhaus teaches that library size is the single most important determinant of antibody diversity and affinity but creating such large yeast antibody libraries is quite time and labor intensive (p. 24, right col., par. 2). Because Fabs are composed of two distinct polypeptide chains, it is possible to encode the two chains on different vectors and in different yeast strains and the two chains can then be brought together in a single diploid yeast by mating, which is a highly efficient process (p. 24, right col., par. 2; Fig. 1). To this end, Weaver-Feldhaus reports the construction of yeast vectors and strains for large heterodimeric Fab libraries by maturing Saccharomyces cerevisiae (Id.). Specifically, Weaver-Feldhaus teaches that the library can be used to rapidly construct large Fab libraries from which multiple high affinity Fab can be isolated (Id.).
Therefore, because ‘846 differs in that it does not teach a diploid yeast host cell and because Weaver-Feldhaus teaches that yeast antibody libraries can be generated in diploid yeast host cells such as Saccharomyces cerevisiae, it would have been obvious to have modified ‘846 such that the yeast cell is diploid. There would have been a reasonable expectation of success because Weaver-Feldhaus teaches that diploid antibody expressing yeast cells can be used to rapidly construct large libraries resulting in a system with rapid affinity maturation or humanization and should significantly facilitate the generation of reagent, diagnostic, and therapeutic antibodies (p. 34, left col., par. 3).
Regarding claim 85, ‘846’s specification defines the structures of the CH and Fc to include IgG1 (col. 13, lines 1-7; col. 14, lines 57-63).
Regarding claim 87, applicant has elected a cell surface anchor polypeptide comprising between 400 to 700 amino acids. ‘846 teaches a bait comprising the human Fc immunoglobulin domain fused to a SED1 polypeptide (SEQ ID NO: 4) which is 570 amino acids in length (i.e., a cell surface anchor polypeptide comprising between 400 to 700 amino acids).
Regarding claim 91, as discussed above, ‘846 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘846 also teaches that the polynucleotides may be associated with heterologous sequences (col. 8, lines 53-62).
Regarding claim 99, as discussed above, ‘846 teaches Saccharomyces cerevisiae (claims 1, 4-5, 9-12, 15, 19, and 39).
Regarding claim 100, ‘846 teaches the non-tethered and monovalent antibodies (claim 2)
Although portions of this rejection rely on the content of the specification of ‘846, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (MPEP § 804(II)(B)(1)). For at least the reasons discussed above, the relevant portions of the specification either define the invention as encompassing the instantly claimed subject matter or provide support for obvious variations of ‘846’s inventions.
Claim 86 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,365,846 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Wang et al. (Protein & Cell, 2018, Vol. 9(1), pages 63-73).
The teachings of ‘846 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 86, the instant claim differs because neither ‘846 nor Weaver-Feldhaus teach that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Wang teaches that therapeutic monoclonal antibodies are among the most effective biotherapeutics to date and one important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions (abstract). Wang reviews various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype (Id.). Wang teaches that IgGs contain a conserved glycosylation site at amino acid N297 in the CH2 domain (p. 66, right col., par. 3). For cases where mAbs are intended to engage cell surface receptors and prevent receptor-ligand interactions, it may be desirable to reduce or eliminate effector function (p. 68, left col., par. 2). An early approach to reduce effector function was to mutate the glycosylation site at N297 with mutations such as N297A (p. 68, left col., par. 3). Wang teaches that this N297 is with EU numbering (p. 64, left col., par. 1).
Thus, because ‘846 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell expressing an Fc domain and CH as well as a bait, it would have been particularly advantageous to have reduced effector function (“for cases where mAbs are intended to engage cell surface receptors”). Accordingly, it would have been obvious to have further modified ‘846’s yeast host cell such that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Claim 88 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,365,846 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Gnanasundram et al. (Molecular Biology of the Cell, 2014, Vol. 26, pages 762-768).
The teachings of ‘846 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 88, as discussed above, ‘846 in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. ‘846 teaches that the host cell comprises a polynucleotide encoding the bait which is operably associated with a regulatable promoter (claims 1, 4-5, and 9-12).
The instant claim differs because neither ‘846 nor Weaver-Feldhaus teaches that the regulatable promoter is a TetO7 promoter.
Gnanasundram et al. teaches that protein depletion is a widely used approach for studying functions of essential genes and a protein can be depleted by for example repression of the gene’s promoter, degradation or inhibitions of its mRNA translation, or destabilization and degradation of the protein itself (p. 762, left col., par. 1). Among the repressible promoters taught by Gnanasundram is TetO7 (Id.). Gnanasundram teaches the development of enhanced TetO7 repressible promoters in S. cerevisiae (abstract; p. 767, left col., par. 3) and teaches that its promoters represent a valuable improvement on existing protein depletion systems and greatly reduce the time required for an efficient depletion of a studied target protein (p. 766, right col., par. 2 through p. 767, left col., par. 1). Additionally, the use of TetO7 does not require a change in growth conditions which could affect processes under investigation (p. 767, left col., par. 1).
Thus, because ‘846 and Weaver-Feldhaus render obvious a bait which is operably associated with a regulatable promoter and because Gnanasundram teaches that in yeast such as S. cerevisiae, TetO7 promoters can be used to rapidly deplete (i.e., operably regulate) expression, it would have been obvious to have further modified ‘846 such that the regulatable promoter is TetO7. There would have been a reasonable expectation of success because ‘846 teaches a generic regulatable promoter associated with S. cerevisiae (i.e., is not limited to a single promoter) and because TetO7 was previously known to be useful in yeast such as S. cerevisiae for rapid regulation of protein expression.
Thus, claim 88 is unpatentable over ‘846 in view of Weaver-Feldhaus and Gnanasundram.
Claims 93-94 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,365,846 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Furukawa et al. (Biotechnology Progress, 2006, Vol. 22, pages 994-997).
The teachings of ‘846 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 93-94, as discussed above, ‘846 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘846 also teaches that the polynucleotides may be associated with heterologous sequences (col. 7, lines 53-62).
The instant claims differ because neither ‘846 nor Weaver-Feldhaus teach that the heterologous protein:
(93) is a minisatellite-like repeat sequence from a yeast cell wall protein; or
(94) that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
Furukawa et al. teaches that there have been numerous studies of expression systems for the display of heterologous proteins on the cell surface of microorganisms (such as in combinatorial library construction in S. cerevisiae)(p. 994, left col., par. 1). And to display proteins on the cell surface of S. cerevisiae, native cell wall proteins such as α-agglutinin and Flo1 with a serine/threonine rich hydrophobic tail for glycosylation and a glycosylphosphatidylinositol (GPI) anchor attachment signal at the C-terminus have been used (Id.).
Thus, because ‘846 in view of Weaver-Feldhaus renders obvious a surface display system comprising a diploid yeast host cell and a bait comprising SED1, it would have been obvious to have further modified the system such that the polynucleotide is also associated with a heterologous sequence such as FLO1. There would have been a reasonable expectation of success because Furukawa demonstrates this protein as being useful in protein presentation systems, particularly in the “extensively studied” S. cerevisiae for library construction.
Thus, claims 93-94 are unpatentable over ‘846 in view of Weaver-Feldhaus and Furukawa.
Claims 97-98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,365,846 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and de Ruijter et al. (Microbial Cell Factories, 2016, Vol. 15(87), pages 1-18).
The teachings of ‘846 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 97-98, as discussed above, ‘846 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein.
However, neither ‘846 nor Weaver-Feldhaus teach:
(97) that the second and third polynucleotides are each operably linked to a second regulatable promoter; or
(98) that the second regulatable promoter is a GAL1 promoter.
de Ruijter teaches an S. cerevisiae “IgG factory” (p. 4, right col., par. 1). Specifically, de Ruijiter provides a system harboring a plasmid for IgG gene integration wherein the plasmid contained genes for heavy and light chains each under GAL1-promoter (p. 14, left col., par. 2).
Accordingly, because ‘846 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell system comprising polynucleotides which are associated with heterologous sequences and because de Ruijter teaches the creation of plasmids harboring GAL1-promoters associated with light and heavy chains (corresponding to the second and third polynucleotides), it would have been obvious to have modified ‘846 in the same way in order to arrive at a diploid yeast host cell wherein the second and third polynucleotides are each operably linked to a second regulatable promoter such as GAL1. There would have been a reasonable expectation of success because de Ruijter teaches the existence of such systems and teaches that such systems are suitable to regulate IgG expression (Fig. 6). This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claims 97-98 are obvious over ‘846 in view of Weaver-Feldhaus and de Ruijter.
Claims 44, 85, and 99-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
The ‘378 patent is directed to:
An antibody display system comprising an isolated host cell (claims 1-3);
A method for determining if an antibody specifically binds to an antigen (claims 4-7);
A method for making an antibody display system (claim 8);
A method for making an antibody (claim 9);
A method for determining the effect of a sugar on an antibody (claim 10); and
A method for determining whether a mutation in an immunoglobulin heavy chain Fc region increases or decreases binding of said chain to an Fc receptor (claim 11).
Regarding claim 44, ‘378 teaches an antibody display system comprising an isolated host cell such as Pichia or S. cerevisiae (i.e., a yeast host cell). ‘378 also teaches a polynucleotide encoding a bait comprising a heavy Fc immunoglobulin domain fused to a surface anchor polypeptide operably associated with a regulatable promoter;
one or more polynucleotides encoding an immunoglobulin light chain region; and
one or more polynucleotides encoding an immunoglobulin heavy chain region.
Accordingly, the claims differ in that ‘378 does not specify the ploidy of the yeast cell.
Weaver-Feldhaus et al. teaches that creating reagents which bind with high specificity and affinity to relevant biomolecules is one of the most critical and challenging tasks facing biologists (p. 24, left col., par. 1). Weaver-Feldhaus teaches that library size is the single most important determinant of antibody diversity and affinity but creating such large yeast antibody libraries is quite time and labor intensive (p. 24, right col., par. 2). Because Fabs are composed of two distinct polypeptide chains, it is possible to encode the two chains on different vectors and in different yeast strains and the two chains can then be brought together in a single diploid yeast by mating, which is a highly efficient process (p. 24, right col., par. 2; Fig. 1). To this end, Weaver-Feldhaus reports the construction of yeast vectors and strains for large heterodimeric Fab libraries by maturing Saccharomyces cerevisiae (Id.). Specifically, Weaver-Feldhaus teaches that the library can be used to rapidly construct large Fab libraries from which multiple high affinity Fab can be isolated (Id.).
Therefore, because ‘378 differs in that it does not teach a diploid yeast host cell and because Weaver-Feldhaus teaches that yeast antibody libraries can be generated in diploid yeast host cells such as Saccharomyces cerevisiae, it would have been obvious to have modified ‘378 such that the yeast cell is diploid. There would have been a reasonable expectation of success because Weaver-Feldhaus teaches that diploid antibody expressing yeast cells can be used to rapidly construct large libraries resulting in a system with rapid affinity maturation or humanization and should significantly facilitate the generation of reagent, diagnostic, and therapeutic antibodies (p. 34, left col., par. 3).
Regarding claim 85, ‘378’s specification defines the structures of the CH and Fc to include IgG1 (col. 12, line 60 through col. 13, line 2).
Regarding claim 99, as discussed above, ‘378 teaches Saccharomyces cerevisiae (claims 1, 4, 8-11).
Regarding claim 100, ‘378 teaches the non-tethered and monovalent antibodies (claims 1 and 3).
Although portions of this rejection rely on the content of the specification of ‘378, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (MPEP § 804(II)(B)(1)). For at least the reasons discussed above, the relevant portions of the specification either define the invention as encompassing the instantly claimed subject matter or provide support for obvious variations of ‘378’s inventions.
Claim 86 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Wang et al. (Protein & Cell, 2018, Vol. 9(1), pages 63-73).
The teachings of ‘378 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 86, the instant claim differs because neither ‘378 nor Weaver-Feldhaus teach that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Wang teaches that therapeutic monoclonal antibodies are among the most effective biotherapeutics to date and one important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions (abstract). Wang reviews various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype (Id.). Wang teaches that IgGs contain a conserved glycosylation site at amino acid N297 in the CH2 domain (p. 66, right col., par. 3). For cases where mAbs are intended to engage cell surface receptors and prevent receptor-ligand interactions, it may be desirable to reduce or eliminate effector function (p. 68, left col., par. 2). An early approach to reduce effector function was to mutate the glycosylation site at N297 with mutations such as N297A (p. 68, left col., par. 3). Wang teaches that this N297 is with EU numbering (p. 64, left col., par. 1).
Thus, because ‘378 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell expressing an Fc domain and CH as well as a bait, it would have been particularly advantageous to have reduced effector function (“for cases where mAbs are intended to engage cell surface receptors”). Accordingly, it would have been obvious to have further modified ‘378’s yeast host cell such that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Claims 87 and 91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Zha et al. (US 2016/0355569 A1).
The teachings of ‘378 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 87 and 91, applicant has elected a cell surface anchor polypeptide comprising between 400 to 700 amino acids. ‘378 teaches a bait comprising the human Fc immunoglobulin domain but does not teach that it is a polypeptide which is 570 amino acids in length.
As discussed above, Zha’s teaches eukaryotes comprising “a polynucleotide encoding the bait which is operably associated with a regulatable promotor”. Zha teaches a bait comprising the human Fc immunoglobulin domain fused to a SED1 polypeptide (SEQ ID NO: 4) which is 570 amino acids in length (i.e., a cell surface anchor polypeptide comprising between 400 to 700 amino acids).
Accordingly, because ‘378 in view of Weaver-Feldhaus teach a bait system located on the extracellular cell membrane surface of the host cell and Zha teaches the same which may comprise a SED1 polypeptide which is 570 amino acids in length, the instant claim is similarly obvious.
Claim 88 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Gnanasundram et al. (Molecular Biology of the Cell, 2014, Vol. 26, pages 762-768).
The teachings of ‘378 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 88, as discussed above, ‘378 in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. ‘378 teaches that the host cell comprises a polynucleotide encoding the bait which is operably associated with a regulatable promoter (claims 3 and 9).
The instant claim differs because neither ‘378 nor Weaver-Feldhaus teaches that the regulatable promoter is a TetO7 promoter.
Gnanasundram et al. teaches that protein depletion is a widely used approach for studying functions of essential genes and a protein can be depleted by for example repression of the gene’s promoter, degradation or inhibitions of its mRNA translation, or destabilization and degradation of the protein itself (p. 762, left col., par. 1). Among the repressible promoters taught by Gnanasundram is TetO7 (Id.). Gnanasundram teaches the development of enhanced TetO7 repressible promoters in S. cerevisiae (abstract; p. 767, left col., par. 3) and teaches that its promoters represent a valuable improvement on existing protein depletion systems and greatly reduce the time required for an efficient depletion of a studied target protein (p. 766, right col., par. 2 through p. 767, left col., par. 1). Additionally, the use of TetO7 does not require a change in growth conditions which could affect processes under investigation (p. 767, left col., par. 1).
Thus, because ‘378 and Weaver-Feldhaus render obvious a bait which is operably associated with a regulatable promoter and because Gnanasundram teaches that in yeast such as S. cerevisiae, TetO7 promoters can be used to rapidly deplete (i.e., operably regulate) expression, it would have been obvious to have further modified ‘378 such that the regulatable promoter is TetO7. There would have been a reasonable expectation of success because ‘378 teaches a generic regulatable promoter associated with S. cerevisiae (i.e., is not limited to a single promoter) and because TetO7 was previously known to be useful in yeast such as S. cerevisiae for rapid regulation of protein expression.
Thus, claim 88 is unpatentable over ‘378 in view of Weaver-Feldhaus and Gnanasundram.
Claims 93-94 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Furukawa et al. (Biotechnology Progress, 2006, Vol. 22, pages 994-997).
The teachings of ‘378 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 93-94, as discussed above, ‘378 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘378 also teaches that the polynucleotides may be associated with heterologous sequences (col. 7, lines 53-62).
The instant claims differ because neither ‘378 nor Weaver-Feldhaus teach that the heterologous protein:
(93) is a minisatellite-like repeat sequence from a yeast cell wall protein; or
(94) that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
Furukawa et al. teaches that there have been numerous studies of expression systems for the display of heterologous proteins on the cell surface of microorganisms (such as in combinatorial library construction in S. cerevisiae)(p. 994, left col., par. 1). And to display proteins on the cell surface of S. cerevisiae, native cell wall proteins such as α-agglutinin and Flo1 with a serine/threonine rich hydrophobic tail for glycosylation and a glycosylphosphatidylinositol (GPI) anchor attachment signal at the C-terminus have been used (Id.).
Thus, because ‘378 in view of Weaver-Feldhaus renders obvious a surface display system comprising a diploid yeast host cell and a bait comprising SED1, it would have been obvious to have further modified the system such that the polynucleotide is also associated with a heterologous sequence such as FLO1. There would have been a reasonable expectation of success because Furukawa demonstrates this protein as being useful in protein presentation systems, particularly in the “extensively studied” S. cerevisiae for library construction.
Thus, claims 93-94 are unpatentable over ‘378 in view of Weaver-Feldhaus and Furukawa.
Claims 97-98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,890,378 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and de Ruijter et al. (Microbial Cell Factories, 2016, Vol. 15(87), pages 1-18).
The teachings of ‘378 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 97-98, as discussed above, ‘378 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein.
However, neither ‘378 nor Weaver-Feldhaus teach:
(97) that the second and third polynucleotides are each operably linked to a second regulatable promoter; or
(98) that the second regulatable promoter is a GAL1 promoter.
de Ruijter teaches an S. cerevisiae “IgG factory” (p. 4, right col., par. 1). Specifically, de Ruijiter provides a system harboring a plasmid for IgG gene integration wherein the plasmid contained genes for heavy and light chains each under GAL1-promoter (p. 14, left col., par. 2).
Accordingly, because ‘378 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell system comprising polynucleotides which are associated with heterologous sequences and because de Ruijter teaches the creation of plasmids harboring GAL1-promoters associated with light and heavy chains (corresponding to the second and third polynucleotides), it would have been obvious to have modified ‘378 in the same way in order to arrive at a diploid yeast host cell wherein the second and third polynucleotides are each operably linked to a second regulatable promoter such as GAL1. There would have been a reasonable expectation of success because de Ruijter teaches the existence of such systems and teaches that such systems are suitable to regulate IgG expression (Fig. 6). This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claims 97-98 are obvious over ‘378 in view of Weaver-Feldhaus and de Ruijter.
Claims 44, 85, 87, 91, and 99-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,106,598 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
The ‘598 patent is directed to:
A method for determining if an antibody specifically binds to an antigen (claim 1); and
Method for identifying an antibody that binds specifically to an antigen or a polynucleotide encoding an immunoglobulin heavy chain of said antibody and/or a polynucleotide encoding an immunoglobulin light chain of said antibody (claims 2-11).
Regarding claim 44, ‘598 teaches an antibody display system comprising an isolated host cell such as Pichia or S. cerevisiae (i.e., a yeast host cell). ‘598 also teaches a polynucleotide encoding a bait comprising a heavy Fc immunoglobulin domain fused to a surface anchor polypeptide operably associated with a regulatable promoter;
one or more polynucleotides encoding an immunoglobulin light chain variable region; and
one or more polynucleotides encoding an immunoglobulin heavy chain variable region.
Accordingly, the claims differ in that ‘598 does not specify the ploidy of the yeast cell.
Weaver-Feldhaus et al. teaches that creating reagents which bind with high specificity and affinity to relevant biomolecules is one of the most critical and challenging tasks facing biologists (p. 24, left col., par. 1). Weaver-Feldhaus teaches that library size is the single most important determinant of antibody diversity and affinity but creating such large yeast antibody libraries is quite time and labor intensive (p. 24, right col., par. 2). Because Fabs are composed of two distinct polypeptide chains, it is possible to encode the two chains on different vectors and in different yeast strains and the two chains can then be brought together in a single diploid yeast by mating, which is a highly efficient process (p. 24, right col., par. 2; Fig. 1). To this end, Weaver-Feldhaus reports the construction of yeast vectors and strains for large heterodimeric Fab libraries by maturing Saccharomyces cerevisiae (Id.). Specifically, Weaver-Feldhaus teaches that the library can be used to rapidly construct large Fab libraries from which multiple high affinity Fab can be isolated (Id.).
Therefore, because ‘598 differs in that it does not teach a diploid yeast host cell and because Weaver-Feldhaus teaches that yeast antibody libraries can be generated in diploid yeast host cells such as Saccharomyces cerevisiae, it would have been obvious to have modified ‘598 such that the yeast cell is diploid. There would have been a reasonable expectation of success because Weaver-Feldhaus teaches that diploid antibody expressing yeast cells can be used to rapidly construct large libraries resulting in a system with rapid affinity maturation or humanization and should significantly facilitate the generation of reagent, diagnostic, and therapeutic antibodies (p. 34, left col., par. 3).
Regarding claim 85, ‘598’s specification defines the structures of the CH and Fc to include IgG1 (col. 2, lines 29-49; col. 13, lines 20-34; col. 15, lines 4-39).
Regarding claim 87, applicant has elected a cell surface anchor polypeptide comprising between 400 to 700 amino acids. ‘598 teaches a bait comprising the human Fc immunoglobulin domain fused to a SED1 polypeptide (SEQ ID NO: 4) which is 570 amino acids in length (i.e., a cell surface anchor polypeptide comprising between 400 to 700 amino acids).
Regarding claim 91, as discussed above, ‘598 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘598 also teaches that the polynucleotides may be associated with heterologous sequences (col. 8, lines 5-14).
Regarding claim 99, as discussed above, ‘598 teaches Saccharomyces cerevisiae (claims 8 and 11).
Regarding claim 100, ‘598 teaches the expression of monovalent antibodies (claims 5)
Although portions of this rejection rely on the content of the specification of ‘598, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (MPEP § 804(II)(B)(1)). For at least the reasons discussed above, the relevant portions of the specification either define the invention as encompassing the instantly claimed subject matter or provide support for obvious variations of ‘598’s inventions.
Claim 86 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,106,598 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Wang et al. (Protein & Cell, 2018, Vol. 9(1), pages 63-73).
The teachings of ‘598 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 86, the instant claim differs because neither ‘598 nor Weaver-Feldhaus teach that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Wang teaches that therapeutic monoclonal antibodies are among the most effective biotherapeutics to date and one important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions (abstract). Wang reviews various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype (Id.). Wang teaches that IgGs contain a conserved glycosylation site at amino acid N297 in the CH2 domain (p. 66, right col., par. 3). For cases where mAbs are intended to engage cell surface receptors and prevent receptor-ligand interactions, it may be desirable to reduce or eliminate effector function (p. 68, left col., par. 2). An early approach to reduce effector function was to mutate the glycosylation site at N297 with mutations such as N297A (p. 68, left col., par. 3). Wang teaches that this N297 is with EU numbering (p. 64, left col., par. 1).
Thus, because ‘598 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell expressing an Fc domain and CH as well as a bait, it would have been particularly advantageous to have reduced effector function (“for cases where mAbs are intended to engage cell surface receptors”). Accordingly, it would have been obvious to have further modified ‘598’s yeast host cell such that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Claim 88 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,106,598 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Gnanasundram et al. (Molecular Biology of the Cell, 2014, Vol. 26, pages 762-768).
The teachings of ‘598 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 88, as discussed above, ‘598 in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. ‘598 teaches that the host cell comprises a polynucleotide encoding the bait which is operably associated with a regulatable promoter (claims 1-2).
The instant claim differs because neither ‘598 nor Weaver-Feldhaus teaches that the regulatable promoter is a TetO7 promoter.
Gnanasundram et al. teaches that protein depletion is a widely used approach for studying functions of essential genes and a protein can be depleted by for example repression of the gene’s promoter, degradation or inhibitions of its mRNA translation, or destabilization and degradation of the protein itself (p. 762, left col., par. 1). Among the repressible promoters taught by Gnanasundram is TetO7 (Id.). Gnanasundram teaches the development of enhanced TetO7 repressible promoters in S. cerevisiae (abstract; p. 767, left col., par. 3) and teaches that its promoters represent a valuable improvement on existing protein depletion systems and greatly reduce the time required for an efficient depletion of a studied target protein (p. 766, right col., par. 2 through p. 767, left col., par. 1). Additionally, the use of TetO7 does not require a change in growth conditions which could affect processes under investigation (p. 767, left col., par. 1).
Thus, because ‘598 and Weaver-Feldhaus render obvious a bait which is operably associated with a regulatable promoter and because Gnanasundram teaches that in yeast such as S. cerevisiae, TetO7 promoters can be used to rapidly deplete (i.e., operably regulate) expression, it would have been obvious to have further modified ‘598 such that the regulatable promoter is TetO7. There would have been a reasonable expectation of success because ‘598 teaches a generic regulatable promoter associated with S. cerevisiae (i.e., is not limited to a single promoter) and because TetO7 was previously known to be useful in yeast such as S. cerevisiae for rapid regulation of protein expression.
Thus, claim 88 is unpatentable over ‘598 in view of Weaver-Feldhaus and Gnanasundram.
Claims 93-94 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,106,598 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Furukawa et al. (Biotechnology Progress, 2006, Vol. 22, pages 994-997).
The teachings of ‘598 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 93-94, as discussed above, ‘598 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘598 also teaches that the polynucleotides may be associated with heterologous sequences (col. 8, lines 5-14).
The instant claims differ because neither ‘598 nor Weaver-Feldhaus teach that the heterologous protein:
(93) is a minisatellite-like repeat sequence from a yeast cell wall protein; or
(94) that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
Furukawa et al. teaches that there have been numerous studies of expression systems for the display of heterologous proteins on the cell surface of microorganisms (such as in combinatorial library construction in S. cerevisiae)(p. 994, left col., par. 1). And to display proteins on the cell surface of S. cerevisiae, native cell wall proteins such as α-agglutinin and Flo1 with a serine/threonine rich hydrophobic tail for glycosylation and a glycosylphosphatidylinositol (GPI) anchor attachment signal at the C-terminus have been used (Id.).
Thus, because ‘598 in view of Weaver-Feldhaus renders obvious a surface display system comprising a diploid yeast host cell and a bait comprising SED1, it would have been obvious to have further modified the system such that the polynucleotide is also associated with a heterologous sequence such as FLO1. There would have been a reasonable expectation of success because Furukawa demonstrates this protein as being useful in protein presentation systems, particularly in the “extensively studied” S. cerevisiae for library construction.
Thus, claims 93-94 are unpatentable over ‘598 in view of Weaver-Feldhaus and Furukawa.
Claims 97-98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,106,598 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and de Ruijter et al. (Microbial Cell Factories, 2016, Vol. 15(87), pages 1-18).
The teachings of ‘598 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 97-98, as discussed above, ‘598 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein.
However, neither ‘598 nor Weaver-Feldhaus teach:
(97) that the second and third polynucleotides are each operably linked to a second regulatable promoter; or
(98) that the second regulatable promoter is a GAL1 promoter.
de Ruijter teaches an S. cerevisiae “IgG factory” (p. 4, right col., par. 1). Specifically, de Ruijiter provides a system harboring a plasmid for IgG gene integration wherein the plasmid contained genes for heavy and light chains each under GAL1-promoter (p. 14, left col., par. 2).
Accordingly, because ‘598 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell system comprising polynucleotides which are associated with heterologous sequences and because de Ruijter teaches the creation of plasmids harboring GAL1-promoters associated with light and heavy chains (corresponding to the second and third polynucleotides), it would have been obvious to have modified ‘598 in the same way in order to arrive at a diploid yeast host cell wherein the second and third polynucleotides are each operably linked to a second regulatable promoter such as GAL1. There would have been a reasonable expectation of success because de Ruijter teaches the existence of such systems and teaches that such systems are suitable to regulate IgG expression (Fig. 6).
Thus, claims 97-98 are obvious over ‘598 in view of Weaver-Feldhaus and de Ruijter.
Claims 44 and 85-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,577,600 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
The ‘600 patent is directed to:
An isolated bait polypeptide comprising a full-length immunoglobulin light chain (claims 1-3); and
An isolated host cell comprising the polypeptide of claim 1 or a polynucleotide encoding said polypeptide.
The claims of ‘600 broadly encompass any isolated host cell comprising an isolated bait polypeptide comprising a full-length immunoglobulin light chain fused to a surface anchor polypeptide or a fragment thereof.
Accordingly, because the instant claims are directed to a yeast host cell which expresses a light chain and surface anchor peptide, the patent is generic to the instant claims and the claims therefore overlap in scope.
Claims 44, 85, 87, 91, and 99-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,104,721 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34).
The ‘721 patent is directed to:
A method for making an antibody comprising culturing an isolated eukaryotic host cell in a growth medium (claims 1-5).
Regarding claims 44 and 87, ‘721 teaches a method for making an antibody comprising using a host which comprises a first and second polypeptide encoding a heavy chain and light chain, and a third polynucleotide encoding a bait comprising a heavy Fc immunoglobulin domain fused to a surface anchor polypeptide on the surface of said eukaryotic host cell (claim 1).
Accordingly, the claims differ in that ‘721 does not specify the ploidy of the yeast cell.
Weaver-Feldhaus et al. teaches that creating reagents which bind with high specificity and affinity to relevant biomolecules is one of the most critical and challenging tasks facing biologists (p. 24, left col., par. 1). Weaver-Feldhaus teaches that library size is the single most important determinant of antibody diversity and affinity but creating such large yeast antibody libraries is quite time and labor intensive (p. 24, right col., par. 2). Because Fabs are composed of two distinct polypeptide chains, it is possible to encode the two chains on different vectors and in different yeast strains and the two chains can then be brought together in a single diploid yeast by mating, which is a highly efficient process (p. 24, right col., par. 2; Fig. 1). To this end, Weaver-Feldhaus reports the construction of yeast vectors and strains for large heterodimeric Fab libraries by maturing Saccharomyces cerevisiae (Id.). Specifically, Weaver-Feldhaus teaches that the library can be used to rapidly construct large Fab libraries from which multiple high affinity Fab can be isolated (Id.).
Therefore, because ‘721 differs in that it does not teach a diploid yeast host cell and because Weaver-Feldhaus teaches that yeast antibody libraries can be generated in diploid yeast host cells such as Saccharomyces cerevisiae, it would have been obvious to have modified ‘721 such that the yeast cell is diploid. There would have been a reasonable expectation of success because Weaver-Feldhaus teaches that diploid antibody expressing yeast cells can be used to rapidly construct large libraries resulting in a system with rapid affinity maturation or humanization and should significantly facilitate the generation of reagent, diagnostic, and therapeutic antibodies (p. 34, left col., par. 3).
Regarding claim 87, applicant has elected a cell surface anchor polypeptide comprising between 400 to 700 amino acids. ‘721 teaches a bait comprising the human Fc immunoglobulin domain fused to a SED1 polypeptide (SEQ ID NO: 4) which is 570 amino acids in length (i.e., a cell surface anchor polypeptide comprising between 400 to 700 amino acids).
Regarding claim 85, ‘721’s specification defines the structures of the CH and Fc to include IgG1 (col. 2, lines 42-61; col. 13, lines 35-49).
Regarding claim 91, as discussed above, ‘721 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘721 also teaches that the polynucleotides may be associated with heterologous sequences (col. 8, lines 18-27).
Regarding claim 99, as discussed above, ‘721 teaches Saccharomyces cerevisiae (claim 4).
Regarding claim 100, ‘721 teaches the expression of monovalent antibodies (claim 1).
Although portions of this rejection rely on the content of the specification of ‘721, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (MPEP § 804(II)(B)(1)). For at least the reasons discussed above, the relevant portions of the specification either define the invention as encompassing the instantly claimed subject matter or provide support for obvious variations of ‘721’s inventions.
Claim 86 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,104,721 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Wang et al. (Protein & Cell, 2018, Vol. 9(1), pages 63-73).
The teachings of ‘721 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 86, the instant claim differs because neither ‘721 nor Weaver-Feldhaus teach that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Wang teaches that therapeutic monoclonal antibodies are among the most effective biotherapeutics to date and one important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions (abstract). Wang reviews various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype (Id.). Wang teaches that IgGs contain a conserved glycosylation site at amino acid N297 in the CH2 domain (p. 66, right col., par. 3). For cases where mAbs are intended to engage cell surface receptors and prevent receptor-ligand interactions, it may be desirable to reduce or eliminate effector function (p. 68, left col., par. 2). An early approach to reduce effector function was to mutate the glycosylation site at N297 with mutations such as N297A (p. 68, left col., par. 3). Wang teaches that this N297 is with EU numbering (p. 64, left col., par. 1).
Thus, because ‘721 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell expressing an Fc domain and CH as well as a bait, it would have been particularly advantageous to have reduced effector function (“for cases where mAbs are intended to engage cell surface receptors”). Accordingly, it would have been obvious to have further modified ‘721’s yeast host cell such that the immunoglobulin Fc domain and the CH comprise an N297A amino acid substitution.
Claim 88 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,104,721 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Gnanasundram et al. (Molecular Biology of the Cell, 2014, Vol. 26, pages 762-768).
The teachings of ‘721 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claim 88, as discussed above, ‘721 in view of Weaver-Feldhaus renders obvious the diploid yeast host cell of claim 44. ‘721 teaches that the host cell comprises a polynucleotide encoding the bait which is operably associated with a regulatable promoter (claims 1-2).
The instant claim differs because neither ‘721 nor Weaver-Feldhaus teaches that the regulatable promoter is a TetO7 promoter.
Gnanasundram et al. teaches that protein depletion is a widely used approach for studying functions of essential genes and a protein can be depleted by for example repression of the gene’s promoter, degradation or inhibitions of its mRNA translation, or destabilization and degradation of the protein itself (p. 762, left col., par. 1). Among the repressible promoters taught by Gnanasundram is TetO7 (Id.). Gnanasundram teaches the development of enhanced TetO7 repressible promoters in S. cerevisiae (abstract; p. 767, left col., par. 3) and teaches that its promoters represent a valuable improvement on existing protein depletion systems and greatly reduce the time required for an efficient depletion of a studied target protein (p. 766, right col., par. 2 through p. 767, left col., par. 1). Additionally, the use of TetO7 does not require a change in growth conditions which could affect processes under investigation (p. 767, left col., par. 1).
Thus, because ‘721 and Weaver-Feldhaus render obvious a bait which is operably associated with a regulatable promoter and because Gnanasundram teaches that in yeast such as S. cerevisiae, TetO7 promoters can be used to rapidly deplete (i.e., operably regulate) expression, it would have been obvious to have further modified ‘721 such that the regulatable promoter is TetO7. There would have been a reasonable expectation of success because ‘721 teaches a generic regulatable promoter associated with S. cerevisiae (i.e., is not limited to a single promoter) and because TetO7 was previously known to be useful in yeast such as S. cerevisiae for rapid regulation of protein expression.
Thus, claim 88 is unpatentable over ‘721 in view of Weaver-Feldhaus and Gnanasundram.
Claims 93-94 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,104,721 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and Furukawa et al. (Biotechnology Progress, 2006, Vol. 22, pages 994-997).
The teachings of ‘721 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 93-94, as discussed above, ‘721 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein. ‘721 also teaches that the polynucleotides may be associated with heterologous sequences (col. 8, lines 5-14).
The instant claims differ because neither ‘721 nor Weaver-Feldhaus teach that the heterologous protein:
(93) is a minisatellite-like repeat sequence from a yeast cell wall protein; or
(94) that the yeast cell wall protein is selected from the group consisting of FLO1, FLO2, and FLO11.
Furukawa et al. teaches that there have been numerous studies of expression systems for the display of heterologous proteins on the cell surface of microorganisms (such as in combinatorial library construction in S. cerevisiae)(p. 994, left col., par. 1). And to display proteins on the cell surface of S. cerevisiae, native cell wall proteins such as α-agglutinin and Flo1 with a serine/threonine rich hydrophobic tail for glycosylation and a glycosylphosphatidylinositol (GPI) anchor attachment signal at the C-terminus have been used (Id.).
Thus, because ‘721 in view of Weaver-Feldhaus renders obvious a surface display system comprising a diploid yeast host cell and a bait comprising SED1, it would have been obvious to have further modified the system such that the polynucleotide is also associated with a heterologous sequence such as FLO1. There would have been a reasonable expectation of success because Furukawa demonstrates this protein as being useful in protein presentation systems, particularly in the “extensively studied” S. cerevisiae for library construction.
Thus, claims 93-94 are unpatentable over ‘721 in view of Weaver-Feldhaus and Furukawa.
Claims 97-98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,104,721 B2 in view of Weaver-Feldhaus et al. (FEBS Letters, 2004, Vol. 564, pages 24-34) and de Ruijter et al. (Microbial Cell Factories, 2016, Vol. 15(87), pages 1-18).
The teachings of ‘721 and Weaver-Feldhaus are set forth above and applied herein.
Regarding claims 97-98, as discussed above, ‘721 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell having a S. cerevisiae SED1 protein.
However, neither ‘721 nor Weaver-Feldhaus teach:
(97) that the second and third polynucleotides are each operably linked to a second regulatable promoter; or
(98) that the second regulatable promoter is a GAL1 promoter.
de Ruijter teaches an S. cerevisiae “IgG factory” (p. 4, right col., par. 1). Specifically, de Ruijiter provides a system harboring a plasmid for IgG gene integration wherein the plasmid contained genes for heavy and light chains each under GAL1-promoter (p. 14, left col., par. 2).
Accordingly, because ‘721 in view of Weaver-Feldhaus renders obvious a diploid yeast host cell system comprising polynucleotides which are associated with heterologous sequences and because de Ruijter teaches the creation of plasmids harboring GAL1-promoters associated with light and heavy chains (corresponding to the second and third polynucleotides), it would have been obvious to have modified ‘721 in the same way in order to arrive at a diploid yeast host cell wherein the second and third polynucleotides are each operably linked to a second regulatable promoter such as GAL1. There would have been a reasonable expectation of success because de Ruijter teaches the existence of such systems and teaches that such systems are suitable to regulate IgG expression (Fig. 6).
Thus, claims 97-98 are obvious over ‘721 in view of Weaver-Feldhaus and de Ruijter.
Conclusion
No claim is allowed.
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/GRANT C CURRENS/Examiner, Art Unit 1651
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