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
Election Response
The Election filed 3/13/2026 in response to the Office Action of 1/15/2026 is acknowledged. Applicant elected with traverse Group I, claims 1, 25-32, 35-40, 42-47, and 86 and the following species:
Targeting domain amino acid sequence, SEQ ID NO: 135
Regulation domain amino acid sequence, SEQ ID NO: 45
Substrate localized in the cytoplasm (claim 28)
The regulation domain is N-terminal to the targeting domain (claim 37)
Targeting moiety is a polypeptide fused to the molecule (claim 47)
Applicants argue that the corresponding international application recognized claim 73 as the same invention as that of Group I, and that claim 7 incorporates all of the limitations of claim 1.
The arguments have been considered but are not persuasive because groups I and II do not relate to a single general inventive concept under PCT Rule 13.2 because they lack the same or corresponding special technical features for the same reasons stated in the Office Action dated 1/15/2026.
Thus, “special technical feature” does not define a contribution over the prior art. For these reasons, the restriction requirement is deemed to be proper and is therefore made FINAL.
Claims 1, 25-32, 35-40, 42-47, 73 and 86 are pending. Claim 73 has been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions. Claims 29, 38 and 46 are withdrawn as being drawn to non-elected species. Claims 1, 25-28, 30-32, 35-37, 39, 40, 42-45, 47 and 86 are currently under prosecution.
Claim Objections
Claims 25-28, 30-32, 35-37, 39-40, and 42-45, and 47 are objected to because of the following informalities: the claims recite “Claim 1”, the “c” in claim does not need to be capitalized. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 25-28, 30-32, 35-37, 39, 40, 42-45, 47 and 86 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claim 1 recites:
A molecule comprising:
A regulation domain comprising an E2 ubiquitin or ubiquitin-like conjugating domain which has an amino acid sequence having at least 80% sequence identity to a human E2 enzyme or a functional part thereof
A targeting domain capable of targeting the regulation domain to a substrate,
wherein the targeting domain has an amino acid sequence at least 80% sequence identity to any one of SEQ ID Nos: 126-135, 138-139, 257 and/or regulation domain has the amino acid sequence having at least 80% sequence identity to any one of SEQ ID Nos: 1-82.
Dependent claim 25 recites that the targeting domain and regulation domains may be variants with up to 20 amino acid modifications, or 30 amino acid modifications, respectively.
Dependent claim 26 recites that the targeting domain is a variant in which one or more lysine residues has been substituted with another amino acid and/or deleted; and/or the regulation domain is a variant in which one or more lysine residues has been substituted with another amino acid and/or deleted.
Thus, the written description is directed to the partial structures of the regulation and partial domains, wherein they can comprise up to 20% sequence discrepancies.
With regards to the regulation domain comprising an E2 ubiquitin, the instant specification discloses that humans have ~41 E2 enzymes. The instant specification discloses that the functional part of the E2 ubiquitin is up to 20 amino acids in length. [pg 21-22; Table 7 and 8] The instant specification discloses the sequences of these enzymes in tables 7 and 8. The specification discloses that the human E2 enzymes have 80% sequence identities to the human E2 enzymes or up to 30 amino acid modifications to minimize auto-ubiquitination and/or increase stability. [pgs 27-28] However, the instant specification does not disclose any representative variants of the regulation domain comprising an E2 ubiquitin that retains function with less than 100% of the claimed sequences.
With regards to the targeting domain, the instant specification discloses that the targeting domain may be: (1) aC63, and discloses these sequences as SEQ ID NO: 126-135, 257; (these sequences are variants of each other) (2) K19 (SEQ ID NO: 138), or (3) E3_5 (SEQ ID NO: 139). (Table 10, pg 116-117). The instant specification discloses that ACS3 which is a monobody that selectively binds to the C-SH2 domain of SHP2, K19 is a DARPin which binds to Kras protein, and E3_5 is a negative control DARPin. [pg 30, lines 4-10; pg 32; 116-117] Thus, the instant specification discloses only three examples of targeting domains that are structurally and functionally diverse sequences and targets. The specification fails to disclose any other representative variants of the broader genus of targeting domains that function as claimed.
It is known in the art discloses that E2 proteins are characterized by a core region of 150 amino acids that are conserved at the level of both sequence and three-dimensional structures. Haldeman et al (Biochemistry 1997, 36, 10526-10537) teaches that certain E2s also have additional regions, which may be up to ~125 residues in length. [pg 10526; Abstract] Haldeman further teaches that deleting amino acid residues of E2 may affect the function of the enzyme, and that core regions have evolved to perform specific functions. [Discussion]
With regards to the use of monobodies, Chandler et al (Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain. Cells. 2020 Mar 4;9(3):610) teaches that monobodies are derived from Type 3 Fibronectin and that although different monobodies maintain the similar Fibronectin structure, they vary widely in their amino acid sequences With regards to DARPins: These protein fragments are composed of a constant region that stabilizes the overall protein folding, and multiple variable regions that mediate binding to a specific target. [see Simeon et al pg 4, 2nd column] DARPins (designed ankyrin repeat proteins) are artificial protein scaffolds based on ankyrin repeat proteins). Simeon teaches that DARPins contain 2-3 internal ankyrin repeats sandwiched between N- and C-terminal capping repeats and each internal AR module consists of 27 defined framework residues. Thus, the structure of the DARPins is essential to the function of the protein.
To provide adequate written description and evidence of possession of the claimed regulation and targeting domain genus, the instant specification can structurally describe representative sequences that function as claimed, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for sequences that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future agents yet to be discovered that may function as claimed.
Applicants have not established any reasonable structure-function correlation with regards to the sequences of the claimed domains that can be altered and still maintain function. Therefore, one could not readily envision members of the broadly claimed genus.
The present claims lack adequate written description and the specification does not provide an adequate written description of each domain that is required to practice the claimed invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 39 and 43 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 43, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 39 recites the limitation "E3 ubiquitin". Claim 39 depends on claim 1, claim 1 does not recite an E3 ubiquitin. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 25-28, 30-32, 36-38, 40, 43-45, 47, and 86 are rejected under 35 U.S.C. 103 as being unpatentable over Vierstra et al (EP0626450 A3; Published 5/1/1996) in view of Matouschek et al (US11008372 B2; Published 11/15/2016) and Friedman et al (WO2003006614 A1; Published 1/23/2003).
Vierstra teaches a molecule comprising: (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate. [Abstract; 0021-0028] Vierstra specifically teaches fusion proteins that includes E2 ubiquitin activity and a protein dinging that has specific affinity to a target protein. Vierstra teaches that this E2 activity allows for proteins to be signaled for degradation. Regarding claims 28 and 30, Vierstra teaches that the substrate “or the target” targets oncogenic signaling proteins and may be localized in the cytoplasm. [Abstract, 0002, 0007, 0029] Regarding claim 36, Vierstra teaches that the molecule is a fusion protein. [0021-0028] Vierstra teaches that the net result is that the amount of the target molecule is dramatically reduced, or practically eliminated. [0008]
However, Vierstra does not teach:
the targeting domain has an amino acid sequence having at least 80% sequence to SEQ ID NO: 135, or that the regulation domain has the amino acid sequence having at least 80% sequence identity to SEQ ID NO: 45,
the substrate may be KRAS (claim 31),
the domains are joined by a linker (claim 32),
the regulation domain is N-terminal to the targeting domain (claim 37)
the molecule comprises a marker (claim 40);
That the molecule is capable of decreasing the amount of a substrate by at least 20% compared to the amount of the substrate in the absence of the molecule; and
The limitations of claim 86, wherein the human E2 enzyme comprises SEQ ID NO: 4.
Matouschek teaches a recombinant polypeptide comprising a proteosome-binding domain (ubiquitin-like domain) and a target-binding domain. [col 1-2] Matouschek teaches that this polypeptide allows to selectively target and degrade proteins bound by the target-binding domain. Regarding claim 27, Matouschek teaches that the substrate is an intracellular polypeptide. [col 2, lines 1-5] [Regarding claims 30 and 31, Matouschek teaches that the target-binding domain binds to an oncogenic protein, such as KRAS. [col 2, lines 50-52; col 9, III target proteins] Regarding claim 32, Matouschek teaches that the regulation domain and the targeting domain are joined by a linker. [col 2, lines 28-29] Regarding claim 37, Matouschek teaches that the target-binding domain is N-terminal to the ubiquitin-like domain. [col 2, lines 15-20] Matouschek teaches that the targeting domain has an amino acid sequence at least 80% sequence identity to instantly claimed SEQ ID NO: 135, and teaches that the one or more lysine residues have been substituted with another amino acid. [see sequence alignments below] Regarding claim 40, Matouschek teaches that the molecule further comprises a detectable marker, such as GFP (Green fluorescent protein, see examples, and figure 2]
RESULT 1
US-15-773-228-15
Sequence 15, US/15773228
Patent No. 11008372
GENERAL INFORMATION
APPLICANT: Board of Regents, the University of Texas System
TITLE OF INVENTION: TARGETING PROTEINS FOR DEGRADATION
FILE REFERENCE: UTSB.P1057US
CURRENT APPLICATION NUMBER: US/15/773,228
CURRENT FILING DATE: 2018-05-03
PRIOR APPLICATION NUMBER: US 62/252,472
PRIOR FILING DATE: 2015-11-07
PRIOR APPLICATION NUMBER: PCT/US2016/060787
PRIOR FILING DATE: 2016-11-07
NUMBER OF SEQ ID NOS: 22
SEQ ID NO 15
LENGTH: 192
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic polypeptide
Query Match 91.0%; Score 465; Length 192;
Best Local Similarity 92.6%;
Matches 87; Conservative 3; Mismatches 4; Indels 0; Gaps 0;
Qy 1 VSSVPTQLEVVAATPTSLLISWDAPAVTVDYYVITYGETGHWPWVWQEFEVPGSYSTATI 60
||||||:|||||||||||||||||||||||||||||||||:||: ||||||||| |||||
Db 99 VSSVPTKLEVVAATPTSLLISWDAPAVTVDYYVITYGETGYWPYYWQEFEVPGSKSTATI 158
Qy 61 SGLHPGVDYTITVYAGSYSSYYYYGSPISINYRT 94
||| |||||||||||||| |||||||||||||||
Db 159 SGLKPGVDYTITVYAGSYDSYYYYGSPISINYRT 192
Freidman teaches the known sequences of E2 ubiquitin (UBE2D1), which matches 100% to the instantly claimed SEQ ID NO: 45. [see sequence alignments below] Freidman teaches that the human E2 enzyme, which matches 100% to instantly claimed SEQ ID NO: 4;: Freidman teaches that the UBE2 protein may be expression as fusion or chimeric protein product. [pg 9, lines 21-25]
RESULT 2
ABP71415
(NOTE: this sequence has 33 duplicates in the database searched)
ID ABP71415 standard; protein; 147 AA.
XX
AC ABP71415;
XX
DT 15-JUN-2007 (revised)
DT 15-MAY-2003 (first entry)
XX
DE Human UBE2 related protein (GenBank Identifier NO. GI#4507773).
XX
KW UBE2; p21; cytostatic; cancer; angiogenic; apoptotic; cell proliferation;
KW human; enzyme; BOND_PC;
KW similar to ubiquitin-conjugating enzyme E2D 1, UBC4/5 homolog; LOC423641;
KW ubiquitin-conjugating enzyme E2D 1; ubiquitin carrier protein;
KW ubiquitin-conjugating enzyme E2-17 kDa 1; stimulator of Fe transport;
KW ubiquitin-conjugating enzyme E2D 1 [Homo sapiens]; UBE2D1; SFT; UBCH5;
KW UBC4/5; UBCH5A; E2(17)KB1;
KW ubiquitin-conjugating enzyme E2D 1, UBC4/5 homolog;
KW ubiquitin-conjugating enzyme E2D 1, UBC4/5 homolog [Mus musculus];
KW MGC28550; LOC608578; hypothetical protein LOC535287;
KW hypothetical protein LOC535287 [Bos taurus]; MGC134214;
KW ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast);
KW ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) [Bos taurus];
KW UB2D1; UB2D1 [Sus scrofa]; LOC780419;
KW ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast), isoform CRA_;
KW unnamed protein product; unnamed protein product [Mus musculus];
KW Ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) [Bos taurus];
KW ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) [Homo sapiens;
KW ubiquitin-conjugating enzyme;
KW ubiquitin-conjugating enzyme [Homo sapiens];
KW ubiquitin conjugating enzyme;
KW ubiquitin conjugating enzyme [Homo sapiens];
KW ubiquitin-conjugating enzyme E2D 1, UBC4/5 homolog (yeast);
KW Ubiquitin-conjugating enzyme E2D 1, UBC4/5 homolog (yeast) [Mus musculus;
KW ubiquitin-conjugating enzyme E2D 1 [synthetic construct]; GO209; GO4842;
KW GO6464; GO6511; GO6512; GO16874; GO31398; GO910; GO4840; GO5515; GO7001;
KW GO7067; GO7125; GO7140; GO7286.
XX
OS Homo sapiens.
XX
CC PN WO2003006614-A2.
XX
CC PD 23-JAN-2003.
XX
CC PF 10-JUL-2002; 2002WO-US021759.
XX
PR 12-JUL-2001; 2001US-0305017P.
PR 10-OCT-2001; 2001US-0328491P.
PR 15-FEB-2002; 2002US-0357452P.
XX
CC PA (EXEL-) EXELIXIS INC.
XX
CC PI Friedman L, Plowman GD, Belvin M;
XX
DR WPI; 2003-229479/22.
DR N-PSDB; ABZ75733.
DR PC:NCBI; gi4507773.
DR PC:SWISSPROT; P51668, P61080, Q2TA10.
DR PC:BIND; 179335, 181938.
XX
CC PT Identifying candidate p21 pathway modulator, by contacting assay system
CC PT having ubiquitin conjugating enzyme or gene with test agent to provide a
CC PT reference activity in system and detecting test agent-biased activity.
XX
CC PS Claim 13; Page 47-48; 51pp; English.
XX
CC The invention relates to identifying candidate p21 pathway modulating
CC agent which involves providing an assay system comprising a purified UBE2
CC polypeptide, nucleic acid or its functionally active fragment or
CC derivative. The identified modulator is useful for modulating a p21
CC pathway of a cell and for diagnosing a disease e.g. cancer in a patient.
CC The identified modulators are useful in diagnosis, therapy and
CC pharmaceutical development. The modulators are useful in a variety of
CC diagnostic and therapeutic applications including angiogenic, apoptotic
CC and cell proliferation disorders. Sequences ABP71415-419 represent
CC sequences related to the UBE2 protein
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 147 AA;
Query Match 100.0%; Score 800; Length 147;
Best Local Similarity 100.0%;
Matches 146; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ALKRIQKELSDLQRDPPAHCSAGPVGDDLFHWQATIMGPPDSAYQGGVFFLTVHFPTDYP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 ALKRIQKELSDLQRDPPAHCSAGPVGDDLFHWQATIMGPPDSAYQGGVFFLTVHFPTDYP 61
Qy 61 FKPPKIAFTTKIYHPNINSNGSICLDILRSQWSPALTVSKVLLSICSLLCDPNPDDPLVP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 FKPPKIAFTTKIYHPNINSNGSICLDILRSQWSPALTVSKVLLSICSLLCDPNPDDPLVP 121
Qy 121 DIAQIYKSDKEKYNRHAREWTQKYAM 146
||||||||||||||||||||||||||
Db 122 DIAQIYKSDKEKYNRHAREWTQKYAM 147
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to construct the molecule of Vierstra wherein the targeting domain or the regulation domain has the amino acid sequence having at least 80% sequence identity to SEQ ID NO: 135 or 45, respectively. One would have been and have a reasonable expectation of success, because: (1) Vierstra teaches a molecule comprising: (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate, (2) Matouschek teaches a recombinant polypeptide comprising a proteosome-binding domain (ubiquitin-like domain) and a target-binding domain, and teaches that the targeting domain has an amino acid sequence at least 80% sequence identity to instantly claimed SEQ ID NO: 135, and (3) Freidman teaches the known sequences of E2 ubiquitin (UBE2D1), which matches 100% to the instantly claimed SEQ ID NO: 45 and teaches that the UBE2 protein may be expression as fusion or chimeric protein product. Given the known methods of constructing a molecule comprising a regulation domain comprising an E2 ubiquitin and a targeting domain capable of targeting the regulation domain to a substrate, and given the known sequences of both domains, one of skilled in the art could have pursued constructing the molecule of Vierstra with the instantly claimed sequence, with a reasonable expectation of success.
It is noted that claim(s) 31, 32, 37 and 40 require: (1) the substrate is KRAS, (2) the domains are joined by a linker (3) regulation domain is N-terminal to the targeting domain, and (4) the molecule comprises a marker, respectively. These limitations would have been obvious to those of ordinary skill in the art because: (1) Vierstra teaches a molecule comprising: (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate, (2) Vierstra teaches that the substrate may be an oncogenic protein, (3) Matouschek teaches a recombinant polypeptide comprising a proteosome-binding domain (ubiquitin-like domain) and teaches that the target-binding domains bind to oncogenic proteins, such as KRAS, and that the domains are joined by a linker, (4) Matouschek teaches that the target binding domain is N-terminal to the ubiquitin-like domain, and (5) Matouschek teaches that the molecule further comprises a detectable marker.
It is noted that claim(s) 44 requires that the molecule is capable of decreasing the amount of a substrate by at least 20% compared to the amount of substrate in the absence of the molecule. This limitation would have been obvious to those of ordinary skill in the art because: (1) Vierstra teaches a molecule comprising: (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate, (2) Vierstra teaches that the net result is that the amount of the target molecule is dramatically reduced, or practically eliminated, (3) Matouschek teaches a recombinant polypeptide comprising a proteosome-binding domain (ubiquitin-like domain), and (4) Matouschek teaches that this polypeptide allows to selectively target and degrade proteins bound by the target-binding domain. Given known methods of constructing molecules for degradation as taught by the prior art, one of skilled in the art could have pursued constructing the molecule of Vierstra wherein the molecule is capable of decreasing the substrate by at least 20%, with a reasonable expectation of success.
Claim(s) 35 is rejected under 35 U.S.C. 103 as being unpatentable over Vierstra et al (EP0626450 A3; Published 5/1/1996), Matouschek et al (US11008372 B2; Published 11/15/2016) and Friedman et al (WO2003006614 A1; Published 1/23/2003) (combined references), as applied to claims 1, 25-28, 30-32, 36-38, 40, 44, 45, 47, and 86 above, and further in view of Trinh R, et al (Optimization of codon pair use within the (GGGGS)3 linker sequence results in enhanced protein expression. Mol Immunol. 2004 Jan;40(10):717-22).
The teachings of the combined references are taught above. However, the references do not teach that the linker comprises the peptide of SEQ ID 145. (claim 35)
Trinh teaches the use of (GGGS)3 linker (instantly claimed SEQ ID NO:145) and known methods of using this linker for protein expression. [Whole document]
It is noted that claim(s) 35 requires the linker to comprise SEQ ID NO: 145. These limitations would have been obvious to those of ordinary skill in the art because: (1) the combined references teach molecules comprising (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate, (2) Matouschek teaches that the domains are joined by a linker, that include glycine and serine residues, and (3) Trinh teaches the use of (GGGS)3 linker (instantly claimed SEQ ID NO:145) and known methods of using this linker for protein expression.
Claim(s) 39 is rejected under 35 U.S.C. 103 as being unpatentable over Vierstra et al (EP0626450 A3; Published 5/1/1996), Matouschek et al (US11008372 B2; Published 11/15/2016) and Friedman et al (WO2003006614 A1; Published 1/23/2003) (combined references), as applied to claims 1, 25-28, 30-32, 36-38, 40, 44, 45, 47, and 86 above, and further in view of Budhidarmo et al (RINGs hold the key to ubiquitin transfer, Trends in Biochemical Sciences, 2011; 37, 58-65).
The teachings of the combined references are taught above. However, the references do not teach that the E2 ubiquitin comprises one or more domains consisting of a RING (Really Interesting New Gene). (claim 39).
Budhidarmo teaches that the RING domain interacts with E2 to promote ubiquitin and highlights the importance of promoting attachment of ubiquitin to proteins, and is an active player in ubiquitin transfer. [Whole document]
It is noted that claim(s) 39 requires E2 ubiquitin comprises one or more domains consisting of a RING (Really Interesting New Gene). These limitations would have been obvious to those of ordinary skill in the art because: (1) the combined references teach molecules comprising (a) a regulation domain comprising an E2 ubiquitin and (b) a targeting domain capable of targeting the regulation domain to a substrate, and (2) Budhidarmo teaches that the RING domain interacts with E2 to promote ubiquitin and highlights the importance of promoting attachment of ubiquitin to proteins, and is an active player in ubiquitin transfer. Given the known methods to construct the instantly claimed molecule, and given the known role of a RING domain in ubiquitination, one could have pursued including a RING domain in the molecule of Vierstra, with a reasonable expectation of success
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/ Examiner, Art Unit 1646
/Zachariah Lucas/ Supervisory Patent Examiner, Art Unit 1600
Prosecution Insights