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
This application is a continuation of PCT/US2023/023863.
Status of Claims
Claims 1-21 are pending.
Claims 1-21 are under examination.
Claim for Domestic Priority
Applicants' claim for domestic priority under 35 USC 119(e) to US provisional application 63/347,802, filed 06/01/2022, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 20, 2026, July 15, 2026, and November 26, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pages 46 and 74+). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 6 is objected to due to the recitation of three internal periods: after “W” in line 7, after “residue” in line 8, and after “(SEQ ID NO:3)” in line 10. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See MPEP 608.01(m).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 and claims 2 and 4-12 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 and recite the limitation “each of which is fused to a biotin ligase peptide substrate”. The metes and bounds of the limitation in the context of the above claim are not clear. (1) It is unclear if “each of which” recited in line 4 refers to the E3 ligase substrate or the ubiquitin or ubiquitin-like molecules. (2) It is unclear if the “biotin ligase peptide substrate” recited in line 4 refers to the ubiquitinated substrate of an E3 ligase recited in line 2 or is another peptide substrate. Appropriate correction is required
Claim 1 and claims 2 and 4-12 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the tagged ubiquitinated E3 ligase" and “tag” in lines 6-7. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not recite a “tag” or “tagged ubiquitinated E3 ligase" in the preceding lines. Therefore, it is unclear what is meant by “tag” and “tagged”. Appropriate correction is required.
Claims 8-9 and claim 10 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 8-9 recite the limitations “at position 183 (K183)… analogous position” and “at position 183… analogous position” The metes and bounds of the limitation in the context of the above claims are not clear. it is unclear what amino acid position corresponds to position 183 because the ligase is not defined by a sequence identifier. The amino acid position corresponding to a specific position can be easily confused depending on how sequences are aligned. Therefore, it is unclear from the specification or from the claims as to what applicants mean by the above limitations. Appropriate correction is required.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: steps (i)-(iii). Claim 10 and claims 1-2 and 7-9 do not recite steps (i)-(iii).
Claim 14 is 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.
Claim 14 recite the limitation “kit or cell comprising composition of claim 1”. The metes and bounds of the limitation in the context of the above claim are not clear. Claim 1 does not recite a composition. Therefore, it is unclear what the kit or cell is compared of. Appropriate correction is required.
Claims 16-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 16-17 contain the trademark/trade name PROTAC®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe proteolysis targeting chimera and, accordingly, the identification/description is indefinite.
Claim 18 is 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.
Claim 18 recites the limitation "the E3 ligase fused.. to a non-promiscuous biotin ligase” in lines 6-7. There is insufficient antecedent basis for this limitation in the claim. Claim 18 depends from claim 13 and claim 13 does not recite an “E3 ligase fused.. to a non-promiscuous biotin ligase”. Appropriate correction is required.
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 1-21 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''
Claims 1-2, 4-12, and 14 have been broadly interpreted to encompass a method of identifying substrates of (A) any E3 ligase or the E3 ligase recited in claim 12 by contacting (B) any substrates of any E3 ligase ubiquitinated with ubiquitin, any ubiquitin-like molecules, or the ubiquitin-like molecules recited in claim 11 fused to (C) any biotin ligase peptide substrate with (E) any biotin ligase, any non-promiscuous biotin ligase, BirA, or the biotin ligase recited in claims 7-10 fused to any E3 ligase or the E3 ligase recited in claim 1.
Claim 3 has been broadly interpreted to encompass a method of identifying a substrate of (A) any E3 ligase or the by (i) expressing in a cell (A) a ubiquitin or any ubiquitin-like molecule fused to (B) any biotin ligase peptide substrate, and (ii) expressing in the cell (C) any E3 ligase fused at the N- or C-terminus of (D) any non-promiscuous biotin ligase.
Claims 13 and 15, 18, and 20-21 have been broadly interpreted to encompass a system or composition comprising (i) (A) a ubiquitin or any ubiquitin-like molecule fused to (B) any biotin ligase peptide substrate or a polynucleotide encoding said ubiquitin or ubiquitin-like molecule and (ii) (C) any E3 ligase fused to (C) any biotin ligase or a polynucleotide encoding said E3 ligase and a method of using said system or composition.
Claim 16 has been broadly interpreted to encompass a system or composition comprising (i) (A) a ubiquitin fused to (B) any biotin ligase peptide substrate or a polynucleotide encoding said ubiquitin and (ii) (C) any E3 ligase fused at the N- or C-terminus to (C) any biotin ligase or a polynucleotide encoding said E3 ligase, and (iii) (D) agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera.
Claim 17 has been broadly interpreted to encompass a method for identifying a target protein by (i) providing a ubiquitin protein fused to (A) any biotin ligase peptide substrate tag or one or more polynucleotides encoding said ubiquitin proteins, (ii) providing (B) any E3 ligase fused at the N- or C- terminus to (C) any biotin ligase, or a polynucleotide encoding said E3 ligase, and (iii) providing (D) agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera.
Claim 19 has been broadly interpreted to encompass a method of identifying a substrate of (A) any E3 ubiquitin ligase by introducing into a cell a polynucleotide encoding (B) any mutant E3 ubiquitin ligase fused to (C) any biotin ligase and expressing the mutant E3 ubiquitin ligase in the cell.
Therefore, the claims are drawn to (A) genus of E3 ligases, (B) genus of E3 ligase substrates, (C) genus of biotin ligases, (D) genus of ubiquitin-like molecules, (E) genus of biotin ligase peptide substrate, and/or (F) genus of agents used in the claimed methods or comprised in the claimed system or composition.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitations of “E3 ligase”, “E3 ligase substrate”, “mutant E3 ubiquitin ligase”, “biotin ligase”, “non-promiscuous biotin ligase” “ubiquitin-like molecule”, “biotin ligase peptide substrate”, and/or “agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera” fails to provide a sufficient description of the genus proteins, enzymes, substrates, and agents used in the claimed method or comprised in the claimed system or composition as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
Yin (US 20200199576 – form PTO-1449) discloses a composition and a method for identifying substrates of E3 ubiquitin ligases (abstract). However, neither Yin nor the prior art teach (1) a composition or method for identifying a substrate of an E3 ligase by contacting (a) an ubiquitinated substrate of ubiquitinated E3 ligase which is fused to a biotin ligase peptide substrate with (b) a biotin ligase fused to the E3 ligase or (2) a composition or method of identifying a substrate an E3 ligase by contacting (a) a ubiquitinated biotin ligase peptide substrate with (b) an E3 ligase fused at the N- or C-terminus of a biotin ligase and tags. Yin discloses that a large number of E3 ligates and their transient interactions with substrates present a significant challenge to identifying the direct and specific substrates of an E3 ligase ([0006]).
The specification is limited to using a CRBN E3 ligase of SEQ ID NO:30 fused at its N- or C-terminus to a BirA (non-promiscuous E. coli wild-type biotin ligase), ubiquitin fused to the peptide substrate of BirA, such as AVI-TAG or A3-tag of SEQ ID NO:2, 7-20, or 21 and proteolysis targeting chimera for the identification of a substrate of the E3 ligase or the identification/screening of a target protein. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the examples described above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
The claimed invention requires a defined set of E3 ligase, E3 ligase substrate, mutant E3 ubiquitin ligase, biotin ligase, non-promiscuous biotin ligase, ubiquitin-like molecule, biotin ligase peptide substrate, and/or agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera. Although the specification discloses exemplary E3 ligase, E3 ligase substrate, mutant E3 ubiquitin ligase, biotin ligase, non-promiscuous biotin ligase, ubiquitin-like molecule, biotin ligase peptide substrate, and/or agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera, a “laundry list” disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species, see Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) or MPEP 2163. While some of the exemplary E3 ligase, E3 ligase substrate, mutant E3 ubiquitin ligase, biotin ligase, non-promiscuous biotin ligase, ubiquitin-like molecule, biotin ligase peptide substrate, and/or agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera were known in the art, this knowledge alone would not allow one level of skill in the art to immediately envisage the claimed genus. Therefore, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which combination of E3 ligase, E3 ligase substrate, mutant E3 ubiquitin ligase, biotin ligase, non-promiscuous biotin ligase, ubiquitin-like molecule, biotin ligase peptide substrate, and/or agent selected from an IMiD, any molecular glue, any reprogramming molecule, or a proteolysis targeting chimera to use in the claimed method or claimed system or composition.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 1-21.
Conclusion
Claims 1-21 are pending.
Claims 1-21 are rejected.
Claim 6 is objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YONG D PAK/Primary Examiner, Art Unit 1652
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