DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/24/2026 has been entered.
Priority
This application claims priority to the U.S. National Stage (371) application of PCT/US2019/067386 filed on 12/19/2019 which claims priority to U.S. Provisional Application No. 62/782,524 filed on 12/20/2018.
Claim Status
Claims 1-2 and 4 and 23 are currently amended, and the Applicant notes that no new matter is added. Claims 3, 6, 14, 19, 21 and 27 are previously presented. Claims 15 and 22 are original. Claims 5, 7-13, 16-18, 20 and 24-26 are cancelled at the Applicant’s request.
Thus, claims 1-4, 6, 14-15, 19, 21-23 and 27 are under examination.
Withdrawn Rejections
The previous rejection of claim 18 under 35 U.S.C. 103, regarding obviousness, is withdrawn in lights of Applicant’s cancellation of the claim.
Maintained Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art (PHOSITA) to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-4, 14, 19 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Tavernier et al. (US 2018/0045719 A1) (Will be cited as “Tavernier 1” hereafter) in view of Fischer et al. (Nature, 2014 Aug 7, 512(7512):49-53) and Che et al. (Bioorganic & Medicinal Chemistry Letters 28 (2018) 2585–2592, Available online 19 April 2018).
Claim 1 recites:
“A method for detecting an interaction between a small molecule/protein complex
and another protein, comprising:
(i) expressing a construct comprising one or more p55 GAG polypeptides fused to a first interaction polypeptide in a cell, wherein the p55 GAG polypeptide forms a virus-like particle;
(ii) incubating the cell or particle with a small molecule library comprising a plurality of small molecules that are not coupled to any of another small molecule, a purification handle, or a bead
(iii) allowing the first interaction polypeptide to interact with the small molecule library and form a small molecule/protein complex;
(iv) allowing a second interaction polypeptide to form a complex with the pre-formed small
molecule/protein complex;
(v) isolating the particle; and
(vi) analyzing the small molecule/protein-protein complex to detect the presence or absence of an interaction between the small molecule/protein complex and another protein,
wherein the first interaction polypeptide is an E3 ligase substrate binding subunit, and
wherein the small molecule library comprises at least one molecular glue and a small molecule of the small molecule library binds to an interaction polypeptide without a recruiting element”.
Regarding claim 1, “Tavernier 1” teaches a method for detecting an interaction between a small molecule/protein complex and another protein (Abstract; page2, [0014]). “Tavernier 1” further teaches expressing a construct comprising one or more p55 GAG protein polypeptides fused to a first interaction polypeptide in a cell (Sheet 1 of 3, figure 1, “GAG-eDHFR”, “GAG-eDHFR expression”; page 2, [0011], “The complexes are trapped via the p55 GAG protein into artificial virus-like particles (VLPs) that are budded from human cells”; page2, [0017-0019]; page 5, [0067], “(1) expressing a VLP-forming polypeptide in a cell”). “Tavernier 1” also teaches that the p55 GAG polypeptide forms a virus-like particle (VLP) (Page 5, [0067], “(1) expressing a VLP-forming polypeptide in a cell”; page 9, claim 3, “wherein the fusion protein comprises HIV p55 GAG protein as VLP-forming polypeptide”). Additionally, “Tavernier 1” teaches incubating the cell or particle with one or more small molecules (Page 5, [0067], “(2) recruiting a fusion construct comprising two small molecules covalently linked to each other, wherein the first small molecule interacts with the VLP-forming polypeptide”). And “Tavernier 1” teaches allowing the first interaction polypeptide to interact with the small molecule and form a small molecule/protein complex (Page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”). “Tavernier 1” also teaches allowing a second interaction polypeptide to form a complex with the pre-formed small molecule/protein complex (Page 5, [0067], “the second small molecule interacts with at least one polypeptide different from the VLP-forming polypeptide”). And “Tavernier 1” teaches isolating the particle (Page 5, [0067], “isolating the VLPs”). “Tavernier 1” further teaches analyzing the small molecule/protein-protein complex to detect the presence of an interaction between the small molecule/protein complex and another protein (Page 5, [0067], “analyzing the entrapped complex”; [0071]). And “Tavernier 1” teaches the small molecule binds to an interaction polypeptide without a recruiting element (Page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”).
Regarding claim 3, “Tavernier 1” teaches the second interaction polypeptide is an endogenous protein or a recombinant protein whose identity or interaction capacity is unknown ([0057], “According to a specific embodiment, the binding partner of the bait molecule (the prey protein) is unknown”; [0063]).
Claim 4 recites:
“A method for detecting a protein-protein interaction, comprising:
(i) expressing a construct comprising one or more p55 GAG polypeptide§. fused to a second interaction polypeptide in a cell, wherein the p55 GAG polypeptide forms a virus-like particle;
(ii) incubating the cell or particle with a small molecule library comprising a plurality of small molecules that are not coupled to any of another small molecule, a purification handle, or a bead
(iii) allowing the small molecule library to interact with a first interaction polypeptide and form a complex;
(iv) allowing the second interaction polypeptide to form a complex with the pre-formed complex
comprising the first interaction polypeptide and the small molecule of the library;
(v) isolating the particle; and
(vi) analyzing the protein-protein complex to detect a protein-protein interaction,
wherein the first interaction polypeptide is an E3 ligase substrate binding subunit, and
wherein the small molecule library comprises at least one molecular glue and a small molecule of the small molecule library binds to an interaction polypeptide without a recruiting element”.
Regarding claim 4, “Tavernier 1” teaches a method for detecting a protein-protein interaction (Abstract; page2, [0014] and [0020]). “Tavernier 1” further teaches expressing a construct comprising one or more p55 GAG protein polypeptide fused to a second interaction polypeptide in a cell (Page2, [0017-0019]; page 3, [0048], “the VLP forming polypeptide is a fusion protein. Thus, according to these embodiments, rather than taking a viral structural protein as such, the protein (or a functional part thereof) is fused to another polypeptide”). “Tavernier 1” also teaches that the p55 GAG polypeptide forms a virus-like particle (VLP) (Page 5, [0067], “(1) expressing a VLP-forming polypeptide in a cell”; page 9, claim 3, “wherein the fusion protein comprises HIV p55 GAG protein as VLP-forming polypeptide.”). And “Tavernier 1” teaches incubating the cell or particle with one or more small molecules (Page 5, [0067], “(2) recruiting a fusion construct comprising two small molecules covalently linked to each other, wherein the first small molecule interacts with the VLP-forming polypeptide”). “Tavernier 1” also teaches allowing the small molecule to interact with a first interaction polypeptide to form a complex (Page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”). And “Tavernier 1” teaches allowing the second interaction polypeptide to form a complex with the pre-formed complex comprising the first interaction polypeptide and the small molecule (Page 5, [0067], “the second small molecule interacts with at least one polypeptide different from the VLP-forming polypeptide”). “Tavernier 1” also teaches isolating the particle (Page 5, [0067], “isolating the VLPs”). And “Tavernier 1” teaches analyzing the protein-protein complex (Page 5, [0067], “analyzing the entrapped complex”). Additionally, “Tavernier 1” teaches that the small molecule binds to an interaction polypeptide without a recruiting element ((Page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”)). Finally, regarding claim 14, “Tavernier 1” teaches that the analyzing is carried out by mass spectrometry (Page 1, [0011]; page 4, [0034]).
Regarding claims 1 and 4, “Tavernier 1” does not teach that a small molecule library comprising a plurality of small molecules that are not coupled to any of another small molecule, a purification handle, or a bead. “Tavernier 1” does not teach that the first interaction polypeptide is an E3 ligase substrate binding subunit and does not teach that the one or more small molecules is a molecular glue. “Tavernier 1” does not teach wherein the small molecule library comprises at least one molecular glue.
Regarding claim 19, “Tavernier 1” does not teach that the small molecule does not interact with the second interaction polypeptide.
Regarding claim 21, “Tavernier 1” does not teach that the E3 ligase substrate binding subunit is selected from cereblon (CRBN) and Von Hippel Lindau (VHL).
Regarding claim 22, “Tavernier 1” does not teach that the E3 ligase substrate binding subunit is associated with a scaffold protein.
Regarding claim 23, “Tavernier 1” does not teach that the scaffold protein is selected from damaged DNA binding protein 1 (DDB1 ), Cullin-4A (CUL4A), regulator of cullins 1 (ROC1), SKIP1, SKP1 interacting partner (SKIP2), Beta-transducin repeats-containing protein (β-TrCP), Double minute 4 protein (MDM4), X-Linked Inhibitor of Apoptosis (XIAP), DDB 1 And CUL4 Associated Factor 15 (DCAF15), and WD Repeat Domain 12 (WDR12).
Regarding claim 1, Fischer teaches a small molecule such as an immunomodulatory drug (IMiDs) that is not coupled to another moiety (Supplementary Methods, page 1, fourth paragraph, “All compounds were dissolved in DMSO at various concentrations”, “In accordance, we observed limited and varying stability for IMiDs especially in cell culture medium and therefore all compounds were frequently quality controlled by mass spectrometry and IMiD containing cell culture medium was always prepared immediately before use”). Fischer teaches a small molecule library of three IMiDs (Abstract). Regarding claims 1 and 4, Fischer teaches using CRBN as an E3 ligase substrate binding subunit (Page 49, left column, “We set out to examine the role of CRBN within the E3 ubiquitin ligase complex”). Also, regarding claim 19, Fischer teaches that a small molecule such as Thalidomide binds only with CRNB as a first interaction polypeptide and not with a second interaction polypeptide (Page 52, figure 5, “a” “Thalidomide binds to CRBN at the canonical substrate-binding site” as compared to “d”). And regarding claim 21, Fischer teaches that the E3 ligase substrate binding subunit is selected from cereblon (CRBN) (Page 49, left column, “We set out to examine the role of CRBN within the E3 ubiquitin ligase complex”). Also, regarding claim 22, Fischer teaches that an E3 ligase substrate binding subunit such as CRBN is associated with a scaffold protein such as CUL4, DDB1 (Abstract). Last, regarding claim 23, Fischer teaches that the scaffold protein is selected from damaged DNA binding protein 1 (DDB1) or from Cullin-4A (CUL4A) (Abstract).
Regarding claims 1 and 4, Che et al. teaches that the small molecule is a molecular glue (Page 2585, right column, first paragraph, “This review will focus on natural products and synthetic small molecules that promote new protein-protein interactions through the ‘‘molecular glue” effect”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the detecting CBRN in the method of Fischer to the method of “Tavernier 1” to increase the detection of protein-protein interactions because Fischer further teaches to characterize the binding of thalidomide as a small molecule to CRBN to detect potential drug resistance in tumor cells (Page 49, left column, second paragraph). A skilled artisan would also then have been motivated to combine the molecular glue concept of Che with the combined method of Fischer and “Tavernier 1” because Che teaches using molecular glue to facilitates transient protein-protein interactions by bringing two proteins in close proximity to each other (Abstract; page 2585, right column, “molecular glue”).
Thus, a skilled artisan would have been motivated to combine the above methods and inventions to characterize transient protein-protein interactions and small molecule binding that are commonly missed. A PHOSITA would have had a reasonable expectation of success in combining the methods of Che, Fischer and “Tavernier 1” based on the methods being in the field of detecting protein-protein interactions. It would have been obvious for a PHOSITA to further characterize the binding of a small molecule and its interaction with different proteins in the method of “Tavernier 1” to identify new interacting proteins for therapeutic purposes.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over “Tavernier 1” et al. (US 2018/0045719 A1) in view of Hihara et al. (US 2007/0134663 A1), Fischer et al. (Nature, 2014 Aug 7, 512(7512):49-53) and Che et al. (Bioorganic & Medicinal Chemistry Letters 28 (2018) 2585–2592, Available online 19 April 2018).
Claim 2 recites:
“A method for detecting a small molecule inhibition or reduction of a protein-protein
interaction, comprising:
(i) expressing a construct comprising one or more p55 GAG polypeptide§ fused to a first interaction polypeptide in a cell, wherein the p55 GAG polypeptide forms a virus-like particle;
(ii) allowing the first interaction polypeptide to interact with a second interaction polypeptide present in the cell;
(iii) incubating the cell or particle with a small molecule library comprising a plurality of small molecules that are not coupled to any of another small molecule, a purification handle, or a bead
(iv) allowing the first interaction polypeptide to interact with the small molecule library;
(v) allowing the second interaction polypeptide to dissociate from the first interaction polypeptide;
(vi) isolating the particle; and
(vii) analyzing the protein-protein complex to detect a small molecule inhibition or reduction of a protein-protein interaction,
wherein the first interaction polypeptide is an E3 ligase substrate binding subunit, and
wherein the small molecule library comprises at least one molecular glue and a small molecule of the small molecule library binds to an interaction polypeptide without a recruiting element”.
Regarding claim 2, ”Tavernier 1” teaches expressing a construct comprising one or more p55 GAG protein polypeptide fused to a first interaction polypeptide in a cell (Sheet 1 of 3, figure 1, “GAG-eDHFR”, “GAG-eDHFR expression”; page 2, [0011], “The complexes are trapped via the p55 GAG protein into artificial virus-like particles (VLPs) that are budded from human cells”; page 2, [0017-0019]; page 5, [0067], “(1) expressing a VLP-forming polypeptide in a cell”). “Tavernier 1” further teaches that the p55 GAG polypeptide forms a virus-like particle (VLP) (Page 5, [0067], “(1) expressing a VLP-forming polypeptide in a cell”; page 9, claim 3, “wherein the fusion protein comprises HIV p55 GAG protein as VLP-forming polypeptide.”). “Tavernier 1” also teaches incubating the cell or particle with one or more small molecules (Page 5, [0067], “(2) recruiting a fusion construct comprising two small molecules covalently linked to each other, wherein the first small molecule interacts with the VLP-forming polypeptide”). And “Tavernier 1” teaches allowing the first interaction polypeptide to interact with the small molecule (Sheet 1 of 3, figure 1, “GAG-eDHFR”, “GAG-eDHFR expression”; page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”). “Tavernier 1” further teaches isolating the particle (Page 5, [0067], “isolating the VLPs”). “Tavernier 1” also teaches analyzing the protein-protein complex (Page 5, [0067], “analyzing the entrapped complex”). And “Tavernier 1” teaches the small molecule binds to an interaction polypeptide without a recruiting element (Page 5, [0067], “wherein the first small molecule interacts with the VLP-forming polypeptide”).
Regarding claim 2, “Tavernier 1” does not teach a method for detecting a small molecule inhibition or reduction of a protein-protein interaction. Also, “Tavernier 1” does not teach allowing the first interaction polypeptide to interact with a second interaction polypeptide present in the cell. And “Tavernier 1” does not teach that a small molecule library comprising a plurality of small molecules that are not coupled to any of another small molecule, a purification handle, or a bead. Also, “Tavernier 1” does not teach allowing the second interaction polypeptide to dissociate from the first interaction polypeptide. “Tavernier 1” does not teach that the first interaction polypeptide is an E3 ligase substrate binding subunit and does not teach that the one or more small molecules is a molecular glue.
Regarding claim 2, Hihara teaches a method for detecting inhibitors of protein-protein interactions (Page 1, [0001]). Hihara further teaches allowing a first interaction polypeptide such as PKC Theta to interact with a second interaction polypeptide such as KPNA1 in a cell (Page 6, [0074]). Hihara also teaches how an inhibitor will prevent a second interaction polypeptide from associating with the first interaction polypeptide or cause their dissociation (Page 1, [0012]; page 4, [0047]).
Regarding claim 2, Fischer teaches a small molecule such as an immunomodulatory drug (IMiDs) that is not coupled to another moiety (Supplementary Methods, page 1, fourth paragraph, “All compounds were dissolved in DMSO at various concentrations”, “In accordance, we observed limited and varying stability for IMiDs especially in cell culture medium and therefore all compounds were frequently quality controlled by mass spectrometry and IMiD containing cell culture medium was always prepared immediately before use”). Fischer teaches a small molecule library of three IMiDs (Abstract). Fischer teaches using CRBN as an E3 ligase substrate binding subunit (Page 49, left column, “We set out to examine the role of CRBN within the E3 ubiquitin ligase complex”).
Regarding claim 2, Che teaches that the small molecule is a molecular glue (Page 2585, right column, first paragraph, “This review will focus on natural products and synthetic small molecules that promote new protein-protein interactions through the ‘‘molecular glue” effect”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine different inhibitors of Hihara with “Tavernier 1” method for identifying protein-protein interactions to improve the method of identifying protein-protein interactions by detecting transient interactions because Hihara used different inhibitors to further characterize protein-protein interactions (Abstract; page 1, [0001]) and studied the interaction of PKC Theta as a first polypeptide with KPNA1 as a second polypeptide (Page 6, [0074]).
A skilled artisan would have been motivated to combine the different polypeptide binding of Fischer with the combined method of Hihara and “Tavernier 1” because Fischer characterized the binding of different polypeptides with a small molecule such as with thalidomide to identify the interaction of endogenous proteins (Abstract). Fischer further teaches using thalidomide to characterize the binding of Thalidomide as a small molecule to a protein such as CRBN to look for drug resistance in tumor cells (Page 49, left column, second paragraph).
A skilled artisan would have been further motivated to combine Che’s concept of molecular glue with the combined methods of Fischer, Hihara and “Tavernier 1” because Che teaches using molecular glue to study transient protein-protein interactions by bringing two proteins in close proximity to each other (Abstract; page 2585, right column, “molecular glue”).
Thus, a skilled artisan would have been motivated to combine the above methods and inventions to better characterize protein-protein interactions such as with PKC signaling in physiological processes. A PHOSITA would have had a reasonable expectation of success in combining the methods of Che, Fischer, Hihara and “Tavernier 1” based on the methods being in the field of detecting protein-protein interactions. It would have been obvious for a PHOSITA to use an inhibitor to protein-protein interactions in the method of “Tavernier 1” to screen for proteins in high-throughput assays for faster identification of interacting proteins.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over “Tavernier 1” et al. (US 2018/0045719 A1), Che et al. (Bioorganic & Medicinal Chemistry Letters 28 (2018) 2585–2592, Available online 19 April 2018) and Fischer et al. (Nature, 2014 Aug 7, 512(7512):49-53) as applied to claims 1 and 14 above, and further in view of Caligiuri et al. (Chemistry & Biology 13, 711–722, July 2006).
Claim 15 recites:
“The method of claim 14, wherein the analyzing comprises comparing mass spectrometry
fingerprints in the presence and absence of the small molecule”.
Regarding claim 15, the teachings of Che, Fischer and “Tavernier 1” are previously discussed.
Regarding claim 15, “Tavernier 1” fails to teach that the analyzing comprises comparing mass spectrometry fingerprints in the presence and absence of the small molecule.
Regarding claim 15, Caligiuri teaches that the analyzing comprises comparing mass spectrometry fingerprints in the presence and absence of the small molecule (Page 713, figure 2, “Detection of Small Molecule-Protein Interactions with MASPIT”, “(A) Small molecules and MFC derivatives used in this study”, “The transfected cells were exposed to Epo in the presence or absence of the MFC”; page 715, right column, second paragraph; page 720, right column, “by enabling a quantitative rather than strictly qualitative mapping of small molecule-protein interaction fingerprints”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine fingerprints analysis method of Caligiuri with the combined methods of Che, Fischer and “Tavernier 1” to improve the method of identifying protein-protein interactions by detecting transient interactions because Caligiuri analyzed the fingerprints of protein-protein interactions and protein small molecule interactions using mass spectrometry (page 720, right column, “by enabling a quantitative rather than strictly qualitative mapping of small molecule-protein interaction fingerprints”). Caligiuri further teaches that structurally related molecules have distinct binding profiles (Page 711, left column, first paragraph) and noted the need to characterize such interactions (Page 711, left column, first paragraph).
Thus, a skilled artisan would have been motivated to combine the above methods and inventions to characterize protein-protein interactions and small molecule binding. A PHOSITA would have had a reasonable expectation of success in combining the methods of Caligiuri, Che, Fischer and “Tavernier 1” based on the methods being in the field of detecting protein-protein interaction. It would have been obvious for a PHOSITA to further characterize the binding of a small molecule and its interaction with different proteins in the method of “Tavernier 1” to achieve an understanding of pathogenesis of various diseases including cancer.
Claims 6 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over “Tavernier 1” et al. (US 2018/0045719 A1), Che et al. (Bioorganic & Medicinal Chemistry Letters 28 (2018) 2585–2592, Available online 19 April 2018) and Fischer et al. (Nature, 2014 Aug 7, 512(7512):49-53) as applied to claims 1 and 4 above, and further in view of “Tavernier 2” et al. (US 2015/0153355 A1).
Claim 6 recites:
“The method of claim 4, wherein the second interaction polypeptide is derived
from a protein, cDNA, and/or open reading frame (ORF) library and whose identity or interaction capacity is unknown”.
Regarding claims 6 and 27, the teachings of “Tavernier 1” are previously discussed.
Regarding claim 6, “Tavernier 1” does not explicitly teach that the second and first interaction polypeptides are derived from a protein respectively.
Regarding claims 6 and 27, “Tavernier 1” does not teach that the FKBP is selected to be FKBP12, and “Tavernier 1” does not teach that the small molecule is selected to be FK506.
Regarding claim 6, “Tavernier 2” teaches that the second interaction polypeptide is derived from a protein (Page 2, [0016]) and whose interaction capacity is unknown and needs to be detected (Page 2, [0019]).
Regarding claim 27, Tavernier 2 teaches that the small molecule is selected to be FK506 (tacrolimus) (Page 6, [0049]).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the detailed method of “Tavernier 2” for studying protein-protein interactions with the combined methods of Che, Fischer and “Tavernier 1” to improve the method of identifying protein-protein interactions by detecting transient interactions because “Tavernier 2” provided a detailed description of the methods used to study protein-protein interactions and defined the proteins to study (Abstract).
Thus, a skilled artisan would have been motivated to combine the above methods and inventions to define protein-protein interactions and small molecule binding. A PHOSITA would have had a reasonable expectation of success based on the methods of Che, Fischer, “Tavernier 1” and “Tavernier 2” being in the field of detecting protein-protein interactions. It would have been obvious for a PHOSITA to further define the binding of a small molecule and its interaction with different proteins in the method of “Tavernier 1” to achieve a higher chance of success with identifying new proteins and small molecules.
Response to Arguments
Applicant's arguments filed 08/24/2026 have been fully considered but they are not persuasive.
The Applicant respectively disagreed with the mere explanation that is provided by Che for a molecular glue and questioned how it will motivate a skilled artisan to arrive at the presently claimed method. The Applicant concluded that there is no teaching in any of the cited references when taken in combination that would motivate a skilled artisan to combine the teaching to arrive the claimed method of the instant application.
This argument is not persuasive because Che not only provides an explanation for a molecular glue but also provides examples of immunomodulatory drugs (Page 2588, right column, second paragraph; page 2588, Fig. 6. Chemical structures of selected IMiDs) which are also discussed by Fischer (Abstract).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the references are all related to studying protein-protein interactions which are also covered by the claims of the instant application. Specifically, Fischer is a secondary reference to combine with the method of “Tavernier 1” to characterize the binding of different polypeptides with a small molecule such as with thalidomide to identify the interaction of endogenous proteins (Abstract). And Che is also a secondary reference to combine with “Tavernier 1” to bring two proteins in close proximity to each other using molecular glue to study transient protein-protein interactions (Abstract; page 2585, right column, “molecular glue”).
Thus, the previous rejections of claims 1-4, 6, 14-15, 19, 21-23 and 27 under 35 U.S.C. 103, regarding obviousness, are maintained.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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