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 .
Claim Status
Claims 1-2, 10, 18, 20-27, and 44-47 are pending.
Claims 3, 6 and 42-43 are newly cancelled.
Claims 1-2, 10, 18, 20-27, and 44-47 remain rejected.
Response to Applicant Arguments – Specification
In response to Applicant’s arguments and amendments to the specification dated 04/14/2026, the objections to the specification of record are withdrawn.
Response to Applicant Arguments - Claim Objections
In response to Applicant’s arguments and amendments to the claims dated 04/14/2026, the claim objections of record are withdrawn. Applicant’s cancellation of claim 43 renders the claim objection against that claim moot and it is withdrawn.
Response to Applicant Arguments - Indefiniteness
In response to Applicant’s arguments and amendments to the claims dated 04/14/2026, the indefiniteness rejections of record are withdrawn. Applicant’s cancellation of claim 3, 6 and 42-43 render the indefiniteness rejections against those claims moot and they are withdrawn.
Response to Applicant Arguments - 35 USC § 101
In response to Applicant’s arguments and amendments to the claims dated 04/14/2026, the 101 rejections of record are withdrawn. Applicant’s cancellation of claim 3, 6 and 42-43 render the rejections against those claims moot and they are withdrawn.
Response to Applicant Arguments – Written Description
In response to Applicant’s arguments and amendments to the claims dated 04/14/2026, the written description rejections of record are withdrawn. Applicant’s cancellation of claim 3, 6 and 42-43 render the rejections against those claims moot and they are withdrawn.
Response to Applicant Arguments – Enablement
In response to Applicant’s arguments and amendments to the claims dated 04/14/2026, the enablement rejections of record are withdrawn. Applicant’s cancellation of claim 3, 6 and 42-43 render the rejections against those claims moot and they are withdrawn.
However, Applicant’s amendments to the claims requires new scope of enablement rejections against the methods of claims 18, 20-23 and 44 and new enablement rejections against claims 24-27 and 45-47.
Claim Rejections - 35 USC § 112 (Enablement)
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.
Scope of Enablement
Claims 18, 20-23 and 44 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of targeted protein degradation using the fusion protein of claim 1 in cells which comprise RPN10 protein, does not reasonably provide enablement for the broad genus of methods of targeted protein degradation of a target protein in any cell or any organism. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
Here, the claims recite a broad genus of methods of targeted protein degradation comprising applying a fusion protein comprising a SAP05 peptide and a distinct target binding moiety which is a T-cell receptor, a cyclic peptide an antibody of an antigen-binding fragment thereof or a nanobody to a sample, cell or organism.
Applicant has provided enabling guidance for methods of targeted protein degradation using SAP05 fusion proteins comprising SAP05 and a GFP-nanobody in A. thaliana protoplasts (Specification, Page 40, Lines 1-8).
However, Applicant also discloses that SAP05 mediated degradation of targets in both plants and in mammalian cells requires the vWA domain containing protein RPN10 (Specification, Page 39, Lines 1-4; Specification, Page 41, Lines 21-32). In fact, Applicant states that “SAP05 is unlikely to interact with PSMD4 the human RPN10 homolog” (Specification, Page 41, Lines 27-32).
Therefore, while Applicant has provided enabled guidance on using a SAP05-GFP-nanobody fusion protein to degrade a target in A. thaliana plant cells containing RPN10, this piece of enabled guidance in the form of a single reduction to practice is insufficient to provide enabled guidance for the broadly claimed genus of methods.
Specifically, Applicant proposes a method of action for SAP05 mediated protein degradation through the 26S proteasome which relies on an active vWA domain in the plant RPN10 protein, however the claimed methods do not mention RPN10 or any other vWA domain containing protein and the broadest reasonable interpretation of the independent claim includes non-plant samples, cells and organisms which would not possess the Arabidopsis thaliana RPN10 which is required for the activity of SAP05 (Specification, Page 41, Lines 27-32).
Given the following facts:
The mechanism described by applicant relies on a specific RPN10 from Arabidopsis thaliana and is not compatible with RPN10 proteins from other species including human orthologs of SAP05 (Specification, Page 38, Line 23-Page 39, Line 4; Specification, Page 41, Lines 27-32).
The claim includes methods drawn to samples, cells and organisms which are not of plant origin.
The specification provides no guidance on SAP05 fusion protein degradation of targets in an Arabidopsis thaliana RPN10 independent manner.
The skilled artisan would be required to use trial and error experimentation in order to make and use the full scope of the claimed methods. Specifically, the skilled artisan would be required to perform all of the experiments described by Applicant in backgrounds not comprising Arabidopsis thaliana RPN10, in order to discover a SAP05 mediated Arabidopsis thaliana RPN10 independent mechanism of protein degradation, if such a mechanism exists. As such applicant’s enabled disclosure of the Arabidopsis thaliana RPN10 dependent SAP05 mediated protein degradation mechanism is simply a starting point and invitation to experiment from which the skilled artisan would be required to perform extensive trial and error experimentation to determine if there were any proteins endogenous to non-plant organisms which filled the role of Arabidopsis thaliana RNP10 or if instead there were conditions under which SAP05 fusion proteins could mediate protein degradation of targets without binding to Arabidopsis thaliana RPB10.
Therefore, while being enabled for the use of SAP05-GFP nanobody fusion proteins to target GFP in A. thaliana cells comprising Arabidopsis thaliana RPN10, the specification does not provide enabled guidance sufficient for a skilled artisan to make and use the full scope of the claimed invention without undue experimentation and therefore claims 18, 20-23 and 44 are rejected.
Claims 24-27 and 47 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In independent claim 24, Applicant claims methods of modulating a biochemical response or physiological response in an organism, the method comprising administering a fusion protein comprising a SAP05 peptide and a distinct target binding moiety which is a T-cell receptor, a cyclic peptide an antibody of an antigen-binding fragment thereof or a nanobody to the organism.
Dependent claim 25 limits the methods of claim 24 to methods where the physiological response is a stress response, immune response, hormone response or light response.
Similarly independent claim 26 is drawn to methods of treating a condition in a patient comprising administering a fusion protein comprising a SAP05 peptide and a distinct target binding moiety which is a T-cell receptor, a cyclic peptide an antibody of an antigen-binding fragment thereof or a nanobody to the patient.
Dependent claims 27 and 47 limit the methods of claim 26 to methods where the condition is characterized by increased expression or activity of a target protein and the target binding moiety is specific for that target protein (claim 27) and to methods where the condition is cancer, an infection , a neurodegenerative disorder or a proteopathy (claim 47).
Applicant has provided enabling guidance for methods of targeted protein degradation using SAP05 fusion proteins comprising SAP05 and a GFP-nanobody in A. thaliana protoplasts (Specification, Page 40, Lines 1-8).
However, Applicant also discloses that SAP05 mediated degradation of targets in both plants and in mammalian cells requires the vWA domain containing protein RPN10 (Specification, Page 39, Lines 1-4; Specification, Page 41, Lines 21-32). In fact, Applicant states that “SAP05 is unlikely to interact with PSMD4 the human RPN10 homolog” (Specification, Page 41, Lines 27-32).
Therefore, while Applicant has provided enabled guidance on using a SAP05-GFP-nanobody fusion protein to degrade a target in A. thaliana plant cells containing Arabidopsis thaliana RPN10, this piece of enabled guidance is insufficient to provide enabled guidance for the claimed methods.
Specifically, Applicant proposes a method of action for SAP05 mediated protein degradation through the 26S proteasome which relies on an active vWA domain in the Arabidopsis thaliana RPN10 protein, however the claimed methods do not mention Arabidopsis thaliana RPN10 or any other vWA domain containing protein and the broadest reasonable interpretation of the independent claims each include non-plant organisms and patients which would not possess endogenous Arabidopsis thaliana RPN10.
Given the following facts:
The mechanism described by applicant relies on a specific RPN10 from Arabidopsis thaliana and is not compatible with RPN10 proteins from other species including human orthologs of SAP05 (Specification, Page 38, Line 23-Page 39, Line 4; Specification, Page 41, Lines 27-32).
The claim includes methods drawn to samples, cells and organisms which are not of plant origin.
The specification provides no guidance on SAP05 fusion protein degradation of targets in an Arabidopsis thaliana RPN10 independent manner.
The skilled artisan would be required to use trial and error experimentation in order to make and use the claimed methods. Specifically, the skilled artisan would be required to perform all of the experiments described by Applicant in backgrounds not comprising Arabidopsis thaliana RPN10, in order to discover a SAP05 mediated Arabidopsis thaliana RPN10 independent mechanism of protein degradation, if such a mechanism exists. As such applicant’s enabled disclosure of the Arabidopsis thaliana RPN10 dependent SAP05 mediated protein degradation mechanism is simply a starting point and invitation to experiment, from which the skilled artisan would be required to perform extensive trial and error experimentation to determine if there were any proteins endogenous to non-plant organisms which filled the role of Arabidopsis thaliana RNP10 or if instead there were conditions under which SAP05 fusion proteins could mediate protein degradation of targets without binding to Arabidopsis thaliana RPN10.
Therefore, the specification does not provide enabled guidance sufficient for a skilled artisan to make and use the claimed invention without undue experimentation and therefore claims 24-27 and 47 are rejected as lacking enablement.
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.
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 1-2, 10, 18, 20-25 and 44-46 are rejected under 35 U.S.C. 103 as being unpatentable over Huang, “Abstracts of Concurrent Session Presentations at IS-MPMI XVIII Congress.” Molecular Plant-Microbe Interactions, vol. 32, no. 10S, Oct. 2019, pp. S1.158 in view of Schmidtke and Caussinus, Drosophila: Methods and Protocols (2016): 177-187.
Claim 1 is drawn to a fusion protein comprising two elements:
A SAP05 peptide.
A targeting moiety which can be a T-cell receptor, a cyclic peptide, an antibody or an antigen-binding fragment thereof, or a nanobody.
With respect to claim 1, Huang teaches the SAP05 polypeptide. Further, Huang teaches that the SAP05 degrades plant transcription factors by hijacking the plant ubiquitin receptor RPN10 and the 26S proteasome (Huang, Page 1.158, Third Abstract).
With respect to claim 1, Huang does not teach a fusion protein comprising the SAP05 polypeptide and a targeting moiety.
With respect to claim 1, Schmidtke, teaches a mechanism for ubiquitin-independent protein degradation that uses RPN10 and the 26S proteasome. The method of Schmidtke centers around FAT10, a ubiquitin-like protein which comprises several important domains including a von Willebrand A domain targeting moiety (Schmidtke, Page 97, Abstract; Schmidtke, Page 99, Column 2, First Paragraph).
Schmidtke teaches that the vWA targeting domain containing protein FAT10 binds to the vWA domain of RPN10 in a ubiquitin independent manner thereby localizing to the 26S proteasome where substrates bound to FAT10 are degraded (Schmidtke, Page 100, Figure 2; Schmidtke, Page 99, Column 2, First Full Paragraph – Page 100, Column 1, First Full Paragraph).
With respect to claim 1, Caussinus which is drawn to the deGradFP system, teaches an effector protein which is a fusion protein comprising a UAS transgene comprising the F-box domain in the N-terminal part of Slmb and the VhhGFP4 GFP-binding nanobody (Caussinus, Page 177, Last Paragraph – Caussinus, Page 178, Second Paragraph; Caussinus, Page 178, Figure 1). The effector protein of the deGradFP system is able to recruit the polyubiquitination system and then the nanobody binds to GFP-labeled target protein which is then degraded by the proteasome.
As such Caussinus teaches the use of a fusion protein for targeted degradation of proteins which comprises a base moiety and a target-binding moiety which is a nanobody.
At the time of filing it would have been obvious to modify the protein of Huang to create a fusion protein with a nanobody as taught in Caussinus in order to use the ubiquitin-independent mechanism of protein degradation Huang and which is detailed in Schmidtke to efficiently and specifically target proteins of interest for degradation. This would have been obvious because all three of these teachings are drawn to protein degradation through the proteasome and joining these teachings is simply combining prior art elements according to known methods to yield predictable results.
Specifically, Caussinus teaches the use of a fusion protein comprising one domain which engages with the ubiquitin-dependent protein degradation machinery and a second domain which is a nanobody and which binds to the target protein thereby targeting that protein of interest for degradation.
Schmidtke details efficient methods of targeted protein degradation that use ubiquitin-like molecules (FAT10) along with RPN10 and the 26S proteasome to degrade target proteins. The method of Schmidtke provides an improvement on the ubiquitin-mediated degradation of target proteins because those methods require modification of the target protein with multiple ubiquitin molecules while a single FAT10 protein is capable of facilitating the degradation of target proteins.
Finally, Huang teaches SAP05 mediated degradation of target proteins in plants which relies on RPN10 and the 26S proteasome. Additionally, Huang teaches that SAP05 requires a specific RPN10 protein and that minor mutations of the plant RPN10 are sufficient to prevent SAP05 function. As such Huang teaches that SAP05 mediated protein degradation has the inherent property of efficient and direct protein degradation without the need for polyubiquitination and has the potential for complex regulation through the use of modified RPN10 proteins.
Given these teachings, at the time of filing the ordinary artisan would have found it obvious to use the SAP05 protein as a base for a fusion protein as taught in Caussinus because of the benefits of the ubiquitin-independent protein degradation mechanism and the ability to modulate function of the fusion protein through transcriptional regulation of the construct encoding the protein but also through the availability of the specific plant RPN10 that SAP05 requires for protein degradation activity. The ordinary artisan would have been motivated to use the GFP-nanobody of Caussinus because this would create a fusion protein system with great adaptability and versatility because rather than creating a unique nanobody or target protein binding domain the single fusion protein would be able to facilitate the degradation of any target that was labeled with GFP. This takes advantage of the large number of GFP-tagged proteins which have been created while analyzing proteins of interest.
The ordinary artisan would have been motivated to make these modifications because they create a protein for use in a targeted protein degradation tool which has multiple levels of regulation, increases efficiency compared to systems which rely on polyubiquitination and provides versatility in the proteins it can target and the systems it can be used in.
As such claim 1 is rejected as obvious under Huang in view of Schmidtke and Caussinus.
With respect to claim 2, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 1, see above.
With respect to claim 10, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 1, see above.
With respect to claim 18, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 1, see above.
With respect to claim 20, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 18 taught above, see above.
With respect to claim 21, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 18 taught above, see above.
Further, Caussinus teaches the targeting of trans-membrane proteins which would be found on the cell surface, similarly Caussinus teaches that this targeting is effective when the fluorescent tag is found in the cytosol and so Caussinus also teaches the targeting of cytosolic proteins (Caussinus, Page 185, Note 5).
With respect to claim 22, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 18 taught above, see above.
With respect to claim 23, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 18 taught above, see above.
Further, Caussinus teaches the targeting of proteins involved in the nervous system and memory generation (Caussinus, Page 186, Note 15).
With respect to claim 24, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 1, see above.
Further, Caussinus teaches the targeting of proteins involved in the nervous system and memory generation (Caussinus, Page 186, Note 15).
With respect to claim 25, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 24, see above.
With respect to claim 44, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 18 taught above, see above.
With respect to claim 45, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 24 taught above, see above.
With respect to claim 46, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 24 taught above see above.
With respect to claims 2, 10, 18, 20-25 and 44-46, Huang, Schmidtke and Caussinus do not explicitly teach a VWA binding moiety that binds to the HS and GA residues at positions 38 and 39 respectively of SEQ ID NO: 21 or corresponding positions in a homologous sequence of a vWA domain, a fusion protein comprising a RPN10 protein or a vWA domain, the use of a fluorescently tagged antibody, targeting Cas9 proteins, physiological responses which are stress responses, immune responses, hormone responses, or light responses, target proteins that are explicitly negatively correlated with yield, and target proteins that are gliadin or glutenin.
With respect to claims 2, 10, 18, 20-25 and 44-46 given the teachings of Huang, Schmidtke and Caussinus it would have been obvious to the ordinary artisan to combine these teachings to arrive at the claimed invention.
In analyzing the obviousness of the instantly claimed invention given the teachings of the prior art it would appear to be helpful to split the limitations in the claims which are not explicitly taught by the references into two groups.
The first group is drawn to limitations which represent inherent properties or obvious modifications of the fusion protein and protein degradation system of Huang in view of Schmidtke and Caussinus. These include vWA binding domains which bind to specific HS and GA residues in vWA domains, the inclusion of a RPN10 protein or a vWA domain in the fusion protein and the use of a fluorescently tagged antibody to tag proteins of interest. First, given that the fusion protein taught by Huang in view of Schmidtke and Caussinus binds to the vWA domain it appears that this binding would inherently involve the claimed residues of the vWA domain. Second, given that the vWA domain of RPN10 is required for SAP05 to degrade target proteins it would have been obvious to and motivating to the ordinary artisan to include at least the vWA domain in the fusion protein in order to increase efficiency by ensuring that the vWA domain required by SAP05 was always in close proximity to the vWA binding domain of SAP05 and given that SAP05 requires a specific vWA domain found in a specific RPN10 this would ensure that this system could be used in organisms which do not comprise endogenous genes encoding the plant RPN10 protein. Finally, given that the fusion protein of Huang in view of Schmidtke and Caussinus relies on an anti-GFP nanobody to bind targets it would have been both obvious to and motivating to the ordinary artisan to use GFP labeled antibodies which bind to target proteins in the protein degradation system. This would have been obvious because one of the limitations of the system of Huang in view of Schmidtke and Caussinus is that the targets must be GFP labeled. By using a GFP-labeled antibody any protein that can be targeted by an antibody could be efficiently degraded using the same fusion protein.
These modifications would have been motivating to the ordinary artisan because they follow the same motivations underlying the construction of the fusion protein. Specifically, they would allow for the fusion protein to more efficiently target a wider range of target proteins for degradation in a variety of backgrounds and cellular contexts.
The second group are limitations drawn to specific target proteins having specific functions. With respect to this second group, as noted above in the obviousness analysis drawn to claim 1, one of the major benefits of the fusion protein of Huang in view of Schmidtke and Caussinus is the ability versatility and ability to easily target a wide range of protein targets which is enabled by the use of an anti-gfp nanobody. Therefore, it would have been obvious to use this fusion protein to degrade any target protein so long as there was motivation to target that protein. In this case the claims refer to targets including Cas9, proteins involved in physiological responses including stress responses, proteins correlated with low yield and plant proteins which can cause severe autoimmune responses when eaten by humans. The ordinary artisan would have been motivated to target all of these proteins.
Targeting Cas9 would allow for rapid degradation of that exogenous protein after it has performed its function which would reduce the risk of off target effects and ensure that no foreign proteins were present in a specific plant or other sample. Targeting stress response proteins and those correlated with low yield would allow for reduced stress responses and higher yields and the degradation of gliadin and/or glutenin creating plants and plant products that do not produce a severe autoimmune response when eaten by humans.
As such claims 2, 10, 18, 20-25 and 44-46 are rejected as obvious under Huang in view of Schmidtke and Caussinus.
Claims 26-27 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Huang, in view of Schmidtke, Caussinus and Zhang, Clinica chimica acta 510 (2020): 802-811.
With respect to claim 26, Huang in view of Schmidtke and Caussinus collectively teach all of the limitations of claim 1, see above.
With respect to claim 26, Huang, Schmidtke and Caussinus do not explicitly teach methods of treating a condition in a patient.
With respect to claim 26, Zhang teaches that the vWA targeting domain containing protein FAT10 which appears to share the same RPN10 dependent mechanism for the targeted degradation of proteins as SAP05 acts in a cardioprotective manner in ischemia and hypoxia by attenuating cardiomyocyte apoptosis, demonstrating a role for vWA domain binding ubiquitin-like proteins in the treatment of human diseases (Zhang, Page 806, Column 1, Section 4.2) . Further, Zhang teaches that FAT10 may be a cancer biomarker and may act to block the function of MAD2, thereby restrain mitosis and increase the aneuploidy rate in cancer cells (Zhang, Page 806, Column 1, Section 5).
Zhang also teaches that FAT10 mediates the degradation of proteins (Zhang, Page 802, Column 2, First line of First Complete Paragraph).
At the time of filing it would have been obvious to the ordinary artisan to modify the protein and methods of Huang in view of Schmidtke and Caussinus in order to include a vWA domain in the fusion protein to ensure action of the SAP05 protein and to use a GFP-labeled antibody to label the eEF1A1 target protein in order to target eEF1A1 for degradation as taught by Zhang.
Given that Zhang teaches that FAT10 binds to eEF1A1 which inhibits the degradation of that protein through the ubiquitin dependent protein degradation pathway which is closely related to cancer cell proliferation and that Zhang teaches that FAT10 mediates protein degradation it appears that increased degradation of eEF1A1 would prevent cell proliferation and treat cancer in those patients. As such it would have been obvious to use the fusion protein of Huang, Schmidtke and Caussinus with a RPN10 vWA domain to ensure activity to target eEF1A1 bound to a GFP-labeled antibody. This would have been obvious because it is combining prior art elements according to known methods to yield the predictable result of increased degradation of eEF1A1 through the ubiquitin-independent protein degradation pathway and the treatment of cancer in patients.
The ordinary artisan would have been motivated to combine these teachings because Huang in view of Schmidtke and Caussinus teach a fusion protein which relies on a vWA domain from a specific RPN10 protein to target GFP-labeled proteins for degradation through the ubiquitin-independent pathway and Zhang teaches that the protein FAT10 which targets proteins for degradation through the ubiquitin-independent pathway promotes cancer by competing with proteins from the ubiquitin-dependent protein degradation pathway which allows for eEF1A1 to persist in cells. Combining these teachings would lead to methods where the fusion protein of Huang in view of Schmidtke and Caussinus along with a GFP-labeled antibody for eEF1A1 was administered to patients with cancer and the fusion protein and FAT10 degraded eEF1A1 through the ubiquitin-independent protein degradation pathway thereby reduced eEF1A1 protein in the cells and treating cancer.
Therefore, claim 26 is rejected as obvious under Huang in view of Schmidtke, Caussinus and Zhang.
With respect to claims 27 and 47, Huang in view of Schmidtke, Caussinus and Zhang collectively teach all of the limitations of claim 26 including treating conditions characterized by increased expression or activity of target proteins, the use of a targeting moiety which binds specifically to that target protein when labeled with an antibody and where the condition is cancer, see above.
Therefore, claims 27 and 47 are rejected as obvious under Huang in view of Schmidtke, Caussinus and Zhang.
Conclusion
All examined claims are rejected.
Finality
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN JAMES SULLIVAN whose telephone number is (571)272-0561. The examiner can normally be reached on 7:30 to 5:00.
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/BRIAN JAMES SULLIVAN/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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