Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Amendments
In the reply filed 06/06/2025, Applicant has amended claims 30-31 and 97-98, canceled claim 99 and newly added claims 100-108.
Election by Original Presentation
Newly submitted/amended claims 105 and 107-108 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Applicant’s response to the Restriction/Election Requirement filed on 06/30/2023 stated Group I, drawn to an ARRDC1 fusion protein, as the elected invention. Accordingly, new claim 105, drawn a method of delivering an agent that belongs to Group IV, is directed to a non-elected invention.
In the response filed on 06/30/2023, Applicant has also elected “a linker for the conjugation of the ARRDC1 protein to a polypeptide” as the elected species. Accordingly, new claims 107-108, drawn to a nucleic acid or a small molecule that is conjugated to the ARRDC1 protein, are directed to a non-elected invention.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 105 and 107-108 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Claim Status
Claims 30-31, 35-38, 96-98 and 100-108 are pending.
Claims 35, 96, 105 and 107-108 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 30-31, 36-38, 97-98, 100-104 and 106 are considered on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/06/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Maintained Claim Objections
Claim 97 stands objected to because of the following informalities:
Claim 97 recites “An ARRDC1 fusion protein of claim 30”, which is recommended to be changed to “The ARRDC1 fusion protein of claim 30” to be consistent with other dependent claims.
New Claim Rejections - 35 USC § 112(a)
NEW MATTER
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 98 and 100-104 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.
Amended claim 98, as well as dependent claims 100-104, recite a new limitation “wherein the polypeptide domain does not comprise … a glutathione S-transferase (GST) domain”. This new limitation represents new matter. In amended cases, subject matter not disclosed in the original application is sometimes added and a claim directed thereto. Such a claim is rejected on the ground that it recites elements without support in the original disclosure under 35 U.S.C. 112, first paragraph, Waldemar Link, GmbH & Co. v. Osteonics Corp. 32 F.3d 556, 559, 31 USPQ2d 1855, 1857 (Fed. Cir. 1994); In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981). See MPEP § 2163.06 - § 2163.07(b) for a discussion of the relationship of new matter to 35 U.S.C. 112, first paragraph. New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.
Specifically, this limitation “wherein the polypeptide domain does not comprise … a glutathione S-transferase (GST) domain” is considered as a negative limitation. A search in the specification did NOT find support for recitation of a glutathione S-transferase (GST) domain. M.P.E.P. §2173.05(i) states that any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) (“[the] specification, having described the whole, necessarily described the part remaining.”). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff ’d mem., 738 F.2d 453 (Fed. Cir. 1984). The mere absence of a positive recitation is not basis for an exclusion. Any claim containing a negative limitation which does not have basis in the original disclosure should be rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. Note that a lack of literal basis in the specification for a negative limitation may not be sufficient to establish a prima facie case for lack of descriptive support. Ex parte Parks, 30 USPQ2d 1234, 1236 (Bd. Pat. App. & Inter. 1993). See MPEP § 2163 - § 2163.07(b) for a discussion of the written description requirement of 35 U.S.C. 112, first paragraph.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 30-31 and 98 under 35 U.S.C. 102 (b) as being anticipated by Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021) is withdrawn in light of Applicant’s amendment to claim 30 to remove “a transcription factor domain” and to claim 98 to recite “the polypeptide domain does not comprise a transcription factor domain”.
Withdrawn Claim Rejections - 35 USC § 103
The prior rejection of claims 30-31, 36-38 and 98 under 35 U.S.C. 103(a) as being unpatentable over Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021) in view of Wikipedia (Two-Hybrid screening, published January 31, 2012. Downloaded from https://en.wikipedia.org/w/index.php?title=Two-hybrid_screening&oldid=474234791, downloaded on 3/14/2024. P. 1-10. Prior art of record) and Stagljar et al., (Proc. Natl. Acad. Sci. USA. 1998; 95: 5187–5192. Prior art of record) is withdrawn in light of Applicant’s amendment to claim 30 to remove “a transcription factor domain” and to claim 98 to recite “the polypeptide domain does not comprise a transcription factor domain”.
New Claim Rejections - 35 USC § 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim 106 is rejected under 35 U.S.C. 102 (b) as being anticipated by Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021).
New independent claim 106 is directed to an ARRDC1 fusion protein comprising an ARRDC1 protein domain or a fragment thereof conjugated to an agent wherein the agent is a protein.
Rauch teaches several ARRDC1 chimeric fusion proteins (p. 3547, left col, last para). For example, Rauch teaches a set of ARRDC1 chimeric fusion proteins for yeast two-hybrid assays, the ARRDC1 fusion proteins comprising an ARRDC1 protein domain or a fragment thereof, that is fused with a VP16 activation domain (i.e., a protein) to form fusion proteins (p. 3547, right col, para 1, see Figs 1B, 3B and 3C legend). In other examples, Rauch teaches an ARRDC1 fusion protein comprising an ARRDC1 protein domain fused with a glutathione S-transferase (GST) (p. 3547, right col, para 1 and p. 3549, left col, para 3, see Fig 2A and Fig 4), or fused with a fluorescent protein (see e.g., Fig 2B for a mCherry-ARRDC1 fusion protein). Thus, Rauch teaches an ARRDC1 fusion protein comprising an ARRDC1 protein domain or a fragment thereof conjugated to an agent wherein the agent is a protein.
Accordingly, Rauch anticipates instant claim 106.
New Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 30-31 and 36-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021) in view of Wikipedia (Two-Hybrid screening, published January 31, 2012. Downloaded from https://en.wikipedia.org/w/index.php?title=Two-hybrid_screening&oldid=474234791, downloaded on 3/14/2024. P. 1-10. Prior art of record), Stagljar et al., (Proc. Natl. Acad. Sci. USA. 1998; 95: 5187–5192. Prior art of record) and Butala et al., (Cell. Mol. Life Sci. 2009; 66: 82-93).
Claim 30 is directed to an ARRDC1 fusion protein comprising an ARRDC1 protein domain or a fragment thereof and a polypeptide domain covalently fused to the ARRDC1 protein domain or fragment thereof, wherein the polypeptide domain comprises a transcriptional repressor domain. It is noted that there is no special definition for the phrase “a transcriptional repressor domain”, thus it is reasonably interpreted as “a domain derived from a transcriptional repressor”.
With respect to claims 30 and 31, Rauch teaches a set of ARRDC1 fusion proteins comprising the ARRDC1 protein domain covalently fused to a polypeptide domain (e.g., a VP16 domain) that are used in the yeast two-hybrid assays to determine the interaction of ARRDC1 with other partners (p. 3547, right col, para 1, and p. 3548, right col, last para), and teaches the ARRDC1 protein fragment comprises a PSAP domain (see Fig 1A, related to claim 31). Rauch teaches the ARRDC1 showed a punctate distribution that was partly relocalized to the plasma membrane, and ARRDC1 can be recruited to the plasma membrane during PPXY-mediated viral budding (p. 3549, left col, para 4; p. 3551, right col; p. 3552, left col; see Fig 5).
However, Rauch does not specifically teach a polypeptide domain comprising a transcriptional repressor domain in claim 30, nor teach the polypeptide domain being fused to the ARRDC1 via a linker or a cleavable linker comprising a protease recognition site in claims 36-38.
Wikipedia teaches the classic yeast two-hybrid screens is limited to soluble proteins and is impossible to use them to study the protein–protein interactions between membrane proteins (p. 5, para “Split-ubiquitin yeast two-hybrid”). To overcome this limitation, Wikipedia refers to a split-ubiquitin system developed by Stagljar et al., in which the membrane proteins of interest are individually fused to two different ubiquitin moieties: a C-terminal ubiquitin moiety ("Cub", residues 35–76) and an N-terminal ubiquitin moiety ("Nub", residues 1–34) (equivalent to the linker in the instant claim 36). In addition to being fused to a membrane protein of interest, the Cub moiety is also fused to a chimeric transcription factor domain that can be cleaved off by ubiquitin specific proteases. Upon interaction between the membrane proteins of interest, Nub and Cub moieties assemble and reconstitute the split-ubiquitin which is recognized by ubiquitin specific protease (Wikipedia, p. 5, para “Split-ubiquitin yeast two-hybrid”. Also see Stagljar Figure 2), thus teaches the linker being a cleavable linker comprising a protease recognition site in claims 37-38.
Regarding the chimeric transcription factor domain (equivalent to the claimed polypeptide domain), Stagljar teaches a chimeric protein A-LexA-VP16 (PLV) was used as the reporter molecule (p. 5187, right col, end of para 2, see Fig 2A). Butala teaches LexA is a bacterial transcriptional repressor, which during normal bacterial growth downregulates its own expression and, in E. coli, the expression of at least 43 unlinked genes (see title, abstract and p. 83, 1st para). Thus, Stagljar teaches in the split-ubiquitin system, the protein of interest is fused to a linker (i.e., a Cub moiety) and further fused to a polypeptide domain (i.e., the protein A-LexA-VP16 reporter), wherein the polypeptide domain comprises a domain derived from a transcriptional repressor (i.e., LexA, as taught by Butala), thus teaches claim 30.
Therefore, it would have been obvious for one of ordinary skill in the art before the time the claimed invention was made to have modified the ARRDC1 fusion protein comprising an ARRDC1 protein covalently fused to a polypeptide for yeast two-hybrid protein-protein interaction assay disclosed by Rauch, by substituting with the split-ubiquitin system comprising covalently fusing the protein of interest to a cleavable linker having a protease recognition site and to a polypeptide reporter domain comprising a domain derived from a transcriptional repressor as taught by Wikipedia, Stagljar and Butala with a reasonable expectation of success. Since Rauch uses yeast two-hybrid assay to screen interaction partners of ARRDC1 and teaches ARRDC1 is recruited to the plasma membrane (p. 3552, left col; see Fig 5), and since Wikipedia and Stagljar teaches the split-ubiquitin system overcomes the limitation of yeast two-hybrid to enable screenings of interactions between membrane proteins, one of ordinary skill in the art would have had a reason to use the split-ubiquitin system, by covalently fusing the protein of interest to a cleavable linker having a protease recognition site and to a polypeptide reporter domain comprising a domain derived from a transcriptional repressor as taught by Wikipedia, Stagljar and Butala, to improve the yeast two-hybrid assay of Rauch to enable studying the protein-protein interactions between the plasma-membrane-localized ARRDC1 and other membrane proteins for its function in viral budding (Rauch, abstract).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 06/06/2025 are acknowledged.
Applicant argues that Rauch does not anticipate the polypeptide domains listed in the amended claim 30 and the combination with Wikipedia and Stagljar fails to teach or suggest all of the features of the amended claim (Remarks, p. 6-7).
Applicant's arguments have been fully considered and they are persuasive. Therefore, the prior 102 rejection by Rauch and 103 rejection over Rauch in view of Wikipedia and Stagljar have been withdrawn. However, as necessitated by amendment, a new ground of rejection has been made over Rauch in view of Wikipedia, Stagljar and Butala as discussed above. Specifically, Stagljar has been reapplied to teach the polypeptide domain comprises a domain derived from a transcriptional repressor LexA as taught by Butala.
Applicant further argues that Rauch does not mention any limitations in the ARRDC1 yeast-two-hybrid system that was used or a limitation involving insoluble integral membrane proteins. Therefore, a person skilled in the art would not have modified the system of Rauch (Remarks, p. 6-7).
Applicant's arguments have been fully considered but they are not persuasive. Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Rauch explicitly teaches the ARRDC1 showed a punctate distribution that was partly relocalized to the plasma membrane upon cotransfection with YFP-WWP1, and ARRDC1 can be recruited to the plasma membrane during PPXY-mediated viral budding (p. 3549, left col, para 4; p. 3551, right col; p. 3552, left col; see Fig 5), thus it would have been obvious to a person skilled in the art to have appreciated that the ARRDC1 protein can be re-localized or recruited to plasma membrane upon protein-protein interaction. Wikipedia teaches the classic yeast two-hybrid screening (that is used by Rauch) is limited to soluble proteins and is impossible to use them to study the protein–protein interactions between membrane proteins and instead suggests a split-ubiquitin system developed by Stagljar et al., (p. 5, para “Split-ubiquitin yeast two-hybrid”). Accordingly, one of ordinary skill in the art would have had a reason to substitute the system of Rauch with the split-ubiquitin system taught by Wikipedia and Stagljar in order to study the protein-protein interactions between plasma-membrane-localized ARRDC1 and other membrane proteins.
Claims 30-31, 97-98 and 100-101 are rejected under 35 U.S.C. 103(a) as being unpatentable over Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021) in view of Huang et al (J. Biochem. Biophys. Methods. 2007; 70: 435-439).
It is noted that the prior rejection of claims 30-31 and 97-98 is maintained. The following rejection is updated to address the newly added claims 100-101.
Claims 30 and 97-98 are directed to an ARRDC1 fusion protein comprising an ARRDC1 protein domain and a polypeptide domain covalently fused to the ARRDC1 wherein the polypeptide domain comprises a phosphatase domain and does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain.
Rauch teaches a set of ARRDC1 fusion proteins comprising the ARRDC1 protein domain covalently fused to a polypeptide domain (e.g., a transcription factor VP16 domain) that are used in the yeast two-hybrid assays to screen the interaction partners of ARRDC1 (p. 3547, right col, para 1, and p. 3548, right col, last para, related to claims 30, 98 and 101). Rauch teaches the ARRDC1 protein domain fragment comprises a PSAP domain (see Fig 1A, related to claims 31 and 100).
However, Rauch is silent on the polypeptide domain comprising a phosphatase domain in claims 30 and 97-98.
Huang teaches a high-sensitive alkaline phosphatase reporter system for screening interaction peptides (abstract). As a demonstration of the method, Huang teaches three streptavidin binding peptides (i.e., proteins to be studied) are genetically fused to an E. coli alkaline phosphatase (EAP) mutant enzyme that has high catalytic activity (related to claims 30 and 97-98), and these EAP-peptide fusion proteins are applied to the streptavidin (i.e., the interaction partner) modified surface to study the binding of the EAP-peptide fusion protein to the interaction partner (abstract, p. 438, right col, Result section, para 3.2, see Fig 3 for colorimetric reaction and Fig 4 for diagram of dilution factor). Huang teaches this improved reporter system enables an efficient, sensitive, rapid and high-throughput screening of the binding of affinity peptides (i.e., protein to be studied) to their receptors (i.e., their interaction partners) (abstract and p. 439, left col, last para).
Therefore, it would have been obvious for one of ordinary skill in the art before the time the claimed invention was made to have modified the ARRDC1 fusion protein comprising an ARRDC1 protein covalently fused to a transcription factor for screening interaction partners of ARRDC1 disclosed by Rauch, by substituting the transcription factor with an alkaline phosphatase as taught by Huang with a reasonable expectation of success. Since Rauch uses the ARRDC1 fusion protein with a transcription factor to screen interaction partners of ARRDC1 (p. 3547, right col, para 1), and since Huang teaches the alkaline phosphatase reporter system, comprising a fusion protein of an alkaline phosphatase covalently fused to the protein to be studied, enables an efficient, sensitive, rapid and high-throughput screening of the binding of the protein to be studied to their interaction partners (abstract and p. 439, left col, last para), one of ordinary skill in the art would have had a reason to use the alkaline phosphatase reporter system, by substituting the transcription factor with an alkaline phosphatase as taught by Huang, to enable an efficient, sensitive, rapid and high-throughput screening of the interaction partners of ARRDC1 (Huang, abstract and p. 439, left col, last para). Furthermore, one of ordinary skill in the art would have understood that the fusion protein suggested by Rauch in view of Huang does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain in claim 98.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 06/06/2025 are acknowledged.
Applicant argues that (1) if a person skilled in the art were to modify Rauch with Huang, ARRDC would be considered to be analogous to the streptavidin of Huang while TSG101 and other proteins are analogous to the streptavidin binding peptides to be modified with alkaline phosphatase. If the streptavidin (the interaction partner) was modified to be a fusion protein with EAP, then each protein to be studied would need to be attached to the surface which would defeat he purpose of the high-throughput system (Remarks, p. 8); (2) there is no reasonable expectation of success because Huang fused the alkaline phosphatase to short peptides while ARRDC1 is a large protein. So although Huang confirms that the fusion of EAP to affinity peptides has little effect on the enzymatic activity of EAP, there is no reasonable expectation of success that the EAP-ARRDC1 fusion protein would be enzymatically active (Remarks, p. 8-9).
Applicant's arguments have been fully considered but they are not persuasive.
In response to Applicant’s first argument, Rauch teaches a yeast two hybrid assay for studying ARRDC1’s interaction partners in which ARRDC1 is either fused to the VP16 activation domain (i.e., as a prey) or fused to the GAL4 DNA binding domain (i.e., as a bait) (see e.g., Fig 1(B) legend). In other words, Rauch does not teach, and a person skilled in the art would not have appreciated, that ARRDC would be considered to be analogous to the streptavidin of Huang while TSG101 and other proteins are analogous to the streptavidin binding peptides to be modified with alkaline phosphatase. Accordingly, Rauch in view of Huang suggest ARRDC1 could have been modified with alkaline phosphatase.
Furthermore, in regard to the argument that if the ARRDC1 was modified to be a fusion protein with EAP, then each protein to be studied would need to be attached to the surface which would defeat the purpose of the high-throughput system, this argument is not persuasive. One of ordinary skill in the art would have appreciated that a protein microarray (or protein chip) is a high-throughput method used to track the interactions of proteins in which a large number of proteins (i.e., each protein to be studied) is immobilized on the support surface, and a probe molecule labeled with a reporter (equivalent to the ARRDC1 fused with EAP) is added to the array for reaction and high-throughput detection. Therefore, it would have been obvious to one of ordinary skill in the art to have modified Rauch’s ARRDC1 fusion protein with Huang’s EAP in order to enable an efficient, sensitive, rapid and high-throughput screening of the interaction partners of ARRDC1.
In response to Applicant’s second argument that there is no reasonable expectation of success that the EAP-ARRDC1 fusion protein of Rauch and Huang would be enzymatically active (Remarks, p. 8-9), as Applicant has correctly stated, Huang explicitly teaches that the fusion of affinity peptides to the c-terminal of EAP has little effect on the enzymatic activity (Huang, p. 438, right col, para 3.1, see Table 1). Therefore, even though Rauch’s ARRDC1 might be larger than Huang’s affinity peptides, one of ordinary skill in the art would still have had a reasonable expectation of success in obtaining an EAP-ARRDC1 fusion protein that is enzymatically active.
Claims 98 and 100-104 are rejected under 35 U.S.C. 103(a) as being unpatentable over Rauch et al (Journal of Virology. 2011; 85: 3546-3556. Cited in IDS 06/30/2021) in view of Lehming (Briefings in functional genomics & proteomics. 2002; 1(3): 230-238).
Claim 98 is directed to an ARRDC1 fusion protein comprising an ARRDC1 protein domain and a polypeptide domain covalently fused to the ARRDC1 wherein the polypeptide domain does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain.
Rauch teaches a set of ARRDC1 fusion proteins comprising the ARRDC1 protein domain covalently fused to a polypeptide domain (e.g., a transcription factor VP16 domain) that are used in the yeast two-hybrid assays to screen for the interaction partners of ARRDC1 (p. 3547, right col, para 1, and p. 3548, right col, last para), or fused to a glutathione S-transferase (GST) or to a fluorescent protein (p. 3547, right col, para 1 and p. 3549, left col, para 3, see e.g., Fig 2A for a GST-ARRDC1 fusion protein and Fig 2B for a mCherry-ARRDC1 fusion protein), related to claims 98 and 101. Rauch teaches the ARRDC1 protein domain fragment comprises a PSAP domain (see Fig 1A, related to claim 100).
However, Rauch does not specifically teach a polypeptide domain that does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain in claim 98, nor teach the polypeptide domain being fused to the ARRDC1 via a linker or a cleavable linker comprising a protease recognition site in claims 102-104.
Lehming summarizes the advantages of a split-ubiquitin system that is used to screen for new interaction partners through development of new reporter proteins (abstract). Specifically, Lehming teaches a genetic system to isolate new binding partners based on conditional degradation, in which the protein of interest (equivalent to the claimed ARRDC1 protein) is fused to a C-terminal ubiquitin moiety (“Y-Cub” in Fig 3B-3C, equivalent to the claimed linker in claim 102) and further fused to a reporter protein Ura3p (whose first amino acid has been replaced by an arginine (RUra3p)) (see p. 232, right col, last para – p. 234, also see Fig 3B-3C). It is noted that the reporter protein Ura3p is an orotidine-5'-phosphate decarboxylase that does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain, thus is related to the polypeptide domain in claim 98. Lehming teaches the interaction partner candidates are fused to an N-terminal ubiquitin moiety ("Nub", see Fig 3C “X-Nub”). If X and Y interact inside the cell, a native-like ubiquitin is formed and the Y-Cub-RUra3p fusion is cleaved by ubiquitin-specific proteases (Ubps) and the protein-protein interaction between X and Y can be detected by the absence of growth on plates lacking uracil and by the growth on plates containing FOA (see p. 234, Fig 3 legend), thus teaches the linker being a cleavable linker comprising a protease recognition site in claims 103-104. Lehming teaches two independent screens have been published using a library of genomic fragments fused to Nub (the interaction partner candidates) and protein of interest fused to Cub-RUra3p (p. 234, left col, equivalent to the claimed ARRDC1), indicating the screening can be performed in a high-throughput manner. Furthermore, Lehming teaches a new reporter, an RGpt2p reporter has been developed that allows for the selection of protein-protein interactions in mammalian cells (p. 235, left col, last para. It is noted that the reporter Gpt2p is a glycerol-3-phosphate acyltransferase that does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain, thus is related to the polypeptide domain in claim 98).
Therefore, it would have been obvious for one of ordinary skill in the art before the time the claimed invention was made to have modified the ARRDC1 fusion protein comprising an ARRDC1 protein covalently fused to a polypeptide for yeast two-hybrid protein-protein interaction assay disclosed by Rauch, by substituting with the split-ubiquitin system comprising covalently fusing the protein of interest to a cleavable linker having a protease recognition site and to a polypeptide reporter domain that does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain as taught by Lehming with a reasonable expectation of success. Since Rauch uses yeast two-hybrid assay to screen for interaction partners of ARRDC1 (p. 3547, right col, para “Yeast two-hybrid screening”), and since Lehming teaches two independent screens have been published using a library of the interaction partner candidates fused to Nub and protein of interest fused to Cub-RUra3p (p. 234, left col), indicating the screening can be performed in a high-throughput manner, and further teaches a new reporter, an RGpt2p reporter, that allows for the selection of protein-protein interactions in mammalian cells (p. 235, left col, last para), one of ordinary skill in the art would have had a reason to use the split-ubiquitin system, by covalently fusing the ARRDC1 to a cleavable linker having a protease recognition site and to a polypeptide reporter domain of RUra3p or RGpt2p that does not comprise a transcription factor domain, a fluorescent protein domain or a GST domain as taught by Lehming to improve the yeast two-hybrid assay of Rauch to enable a high-throughput screening mediated by RUra3p reporter or to enable screenings in mammalian cells mediated by RGpt2p reporter.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 06/06/2025 are acknowledged and have been discussed above.
Maintained Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 30-31, 36-38, 97-98, 100-104 and 106 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7 and 12-14 of US Patent No. 10945954 to Lu (‘954). Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims of ‘954 recite an ARRDC1 protein or fragment thereof, associated with an enzyme (patented claim 1 (i)), the enzyme being selected from kinases, phosphatases, ligases etc (patented claim 2), the enzyme being covalently bound to the ARRDC1 protein or fragment thereof (patented claim 5), the ARRDC1 protein fragment comprising an ARRDC1 PSAP domain (patented claim 7), the enzyme being bound to the ARRDC1 or fragment thereof via a linker (patented claim 12), the linker being a cleavable linker (patented claim 13), the cleavable linker comprising a protease recognition site or a UV-cleavable moiety (patented claim 14).
The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited patent claims, said claims are not patentably distinct.
Claims 98, 101 and 106 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 8, 11, 13-14, 18, 20 and 22 of US Patent No. 11730823 to Lu (‘823). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claims of ‘823 recite an ARRDC1 fusion protein comprising an ARRDC1 protein or a variant, and an RNA binding protein (patented claims 11 and 20), the ARRDC1 fusion protein being encoded by a recombinant expression construct (patented claims 14, 18 and 22). Thus, the patented claims teach the instant claim 106 and are related to claims 98 and 101.
However, the patent claims do not specifically recite the domains being covalently fused via a covalent bond.
Nevertheless, the patent claims recite the ARRDC1 fusion protein being encoded by a recombinant expression construct.
Therefore, it would have been obvious for one of ordinary skill in the art before the time the claimed invention was made to have chosen the ARRDC1 being covalently fused to the transcription factor (e.g., by making an in-frame recombinant expression construct of ARRDC1 and the transcription factor) in the fusion protein of ‘823. One of ordinary skill in the art would have had a reason to do so in order to simplify the step of producing the fusion protein and to ensure the ARRDC1 and the transcription factor being fused to form the claimed fusion protein.
Since the instant application claims are made obvious by cited patent claims, said claims are not patentably distinct.
Provisional Double Patenting Rejections
Claims 30-31, 98, 100-101 and 106 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10, 13, 18, 32 and 57 of copending Application No. 17/764,013 to Lu (‘013). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims of ‘013 recite a minimal ARRDC1 fusion protein comprising a minimal ARRDC1 protein and a Cas9 protein (i.e., a nuclease), and the minimal ARRDC1 protein comprising a PSAP motif (copending claim 57), a minimal ARRDC1 protein or variant thereof, further comprising an agent (copending claims 10 and 13), a receptor tyrosine kinase (copending claim 18), the agent being covalently bound to the minimal ARRDC1 protein or fragment thereof (copending claim 32).
The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are much more specific. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Response to Traversal:
Applicant’s arguments filed on 06/06/2025 are acknowledged.
Applicant argues that claims 30 and 97-99 are amended and thus the reasons for the double patenting rejections are not necessarily applicable to the presently amended claims. Applicant requests the rejections to be reevaluated and withdrawn.
Applicant's arguments have been fully considered but they are not persuasive.
As requested by Applicant, the double patenting rejections have been reevaluated. The rejection over US Patent No. 10945954 is still applicable and thus maintained and updated to address new claims. The rejection over US Patent No. 11730823 is still applicable to claim 98 and thus maintained and is updated to address new claims 101 and 106. The provisional rejection over copending Application No. 17/764,013 is still applicable and thus maintained and updated to address new claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANJIAN ZHU/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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