DETAILED ACTION
Status of the Claims
Claims 76-86, 88, and 92-100 are currently pending.
Claims 1-75, 87, and 89-91 have been canceled by Applicant.
Claim 76 is amended.
Claims 97-100 are new.
Claims 76-86, 88, and 92-100 are the subject of this Office Action.
The following Office Action is in response to Applicant’s communication dated 11/17/2025. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Terminal Disclaimer
The terminal disclaimer filed on 11/17/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of 11,015,266, 10,767,278, 10,760,181, 11,015,265, and any patent granted on Application Number 17/238,150 has been reviewed and is accepted. The terminal disclaimer has been recorded.
New Claim Objections
Necessitated by Amendments
Claims 98-99 are objected to as being dependent upon a rejected base claim, but would be free from the prior art if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Appropriate correction is required.
Modified and New Claim Rejections – 35 U.S.C. 103(a)
Necessitated by Amendments
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.
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.
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.
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 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.
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.
Stuelpnagel et al. and Dower et al.
Claims 76-86, 88, 92-96, and 100 are rejected under 35 U.S.C. 103 as being unpatentable over Stuelpnagel et al. (U.S. PGPub 2002/0150909 A1, cited in IDS of 06/21/2022) in view of Dower et al. (WO 93/06121, of record).
Regarding claim 76(in part), Stuelpnagel discloses an ordered array for use in a high throughput biological screening assay (e.g., as per [0028]), said ordered array comprising a solid support comprising a plurality of wells (e.g., an array of wells as per [0036]-[0042]), wherein each of said plurality of wells further comprises an immobilized microparticle (e.g., microspheres as per [0046]-[0047]), and wherein each of said immobilized microparticles has:
(i) a ligand domain covalently attached via a first functionalized group on the surface of said immobilized microparticle (e.g., termed a “bioactive agent” as per [0052]-[0059], which is covalently attached to the microparticle via a functional group and a linker as per [0068]-[0072] using any of a number of specified chemistries); and
(ii) a nucleic acid domain of the immobilized microparticle (e.g., termed IBL or “identifier binding ligand”, which may be a nucleic acid as per [0074] and/or [0078]),
wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein (e.g., “bioactive agents” can be peptides, proteins, small molecules, etc. as per [0052]-[0059]), and
wherein said nucleic acid domain identifies said ligand domain (e.g., the IBL allows for the identification of the bioactive agent, as per [0092]).
Regarding the “nucleic acid domain” of claim 76, Stuelpnagel discloses an IBL or “identifier binding ligand”, which is a single-stranded nucleic acid in a preferred embodiment (e.g., as per [0078]) and can be used to identify the ligand domain (e.g., as per [0015] and/or [0092] and/or [0183]). Stuelpnagel discloses that the IBL can be identified by binding to a DBL or “decoder binding ligand” (e.g., as per [0073] and/or [0179]-[0183]), wherein this interaction “should be sufficient to remain bound under conditions of the decoding step, including wash steps” (e.g., as per [0073]). However, Stuelpnagel is silent on how the nucleic acid domain is associated with the microparticle, including being silent about being explicitly covalently attached to the surface of the microparticle via a second functionalized group and linker, as well as this second functionalized group being different from the functionalized group used to covalently attach the ligand domain, and wherein the second linker is selectively cleavable with a cleaving agent that does not cleave said first linker, as set forth in claim 76.
Dower discloses microparticles with peptides/polypeptides covalently attached via a first functionalized group and nucleic acid identifier tags covalently attached via a second functionalized group, wherein the first functionalized group is different from the second functionalized group, and wherein the second linker is selectively cleavable with a cleaving agent that does not cleave said first linker (e.g., as per the section II. Method for Producing Tagged Synthetic Oligomer Libraries on pp. 15-19 and depicted in Fig. 3 and/or Example 3 and depicted in Fig. 8). A number of embodiments of Dower are encompassed by the newly added limitations to claim 76. For Fig. 3, the linker for the ligand domain can reasonably correspond to AA1 of Dower, which is the same for all library members, and the linker for the nucleic acid domain can reasonably correspond to two or more of the 3’-terminal nucleotides (e.g., which can be part of the primer binding site as taught by Dower at p. 25, lines 5-7), wherein this second linker is selectively cleavable with a cleaving agent that does not cleave said first linker, for example, by a nucleic acid specific cleaving agent such as an endonuclease, etc.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to produce the ordered array of microparticles of Stuelpnagel using the covalent attachment via differing functionalized groups as per Dower, as well as using differentially cleavable linkers.
In accordance with MPEP § 2141 citing KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385,1395 (2007), "[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”, and as per MPEP § 2143(I)(A), the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. In the present case, all of the elements of the claimed ordered array of microparticles were well known in the art, as per Stuelpnagel and Dower, the mere combining of the individual elements in one embodiment in the manner of the claimed invention results in no change in the elements respective functions, and the combination yields nothing more than predictable results.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since Dower provides the method to successfully covalently couple peptides/polypeptides and nucleic acids to microparticles using orthogonal protecting groups.
Regarding claim 77, Dower discloses the above, wherein said ligand domain is a plurality of ligand domains conjugated to a plurality of said first functionalized groups on the surface of said immobilized microparticle (e.g. as per Fig. 3 and/or Fig. 8).
Regarding claim 78, Dower discloses the above, wherein said nucleic acid domain is a plurality of nucleic acid domains conjugated to a plurality of said second functionalized groups on the surface of said immobilized microparticle (e.g. as per Fig. 3 and/or Fig. 8).
Regarding claim 79, Dower discloses the above, wherein said ligand domain comprises a plurality of chemical building blocks, and wherein said nucleic acid domain comprises a plurality of nucleic acids identifying said plurality of chemical building blocks (e.g. as per Fig. 3 and/or Fig. 8).
Regarding claim 80, Dower discloses the above, wherein each of said first and second functionalized groups is independently selected from the group consisting of an amino group, a carboxyl group, a thiol group, and a hydroxyl group (e.g., as per Fig. 3 and/or Fig. 8, wherein Dower discloses amino, hydroxyl, and thiol groups).
Regarding claim 81, Stuelpnagel discloses the above, wherein said ordered array is screened for activity against a biomolecule selected from the group consisting of a hormone, a cytokine, a protein, an antibody, a nucleic acid, a lipid, a carbohydrate, a cellular membrane antigen, a receptor, a whole cell, a whole cell lysate, a eukaryotic cell, and a virus (e.g., as per [0199]-[0205]). The recitation of “is screened for activity against a biomolecule” of the instant claim 81 is a recitation of intended use of the instant claimed ordered array and a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Please see MPEP 2111.02, citing In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus), and MPEP 2112.01 citing In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) stating that “discovery of an unobvious property and use does not overcome the statutory restraint of section 102 when the claimed composition is known”.
Regarding claim 82, Stuelpnagel discloses the above, wherein said biomolecule is selected from the group consisting of a whole cell, a whole cell lysate, a eukaryotic cell, and any component thereof (e.g., as per [0199]-[0205]).
Regarding claim 83, Stuelpnagel discloses the above, wherein said nucleic acid is mRNA (e.g., as per [0228]).
Regarding claim 84, Stuelpnagel discloses the above, wherein said peptide comprises at least one moiety selected from the group consisting of a naturally occurring amino acid, a non-naturally occurring amino acid, and a mimetic of a naturally occurring amino acid (e.g., peptides with non-naturally occurring amino acids as per [0055]-[0056]).
Regarding claim 85, Stuelpnagel discloses the above, wherein said peptide further comprises a portion having non-peptide functionality (e.g., peptides with “non-amino acid substituents” as per [0056]).
Regarding claim 86, Stuelpnagel discloses the above, wherein said wherein said peptide is selected from the group consisting of a macrocyclic peptide, an acyclic precursor to a macrocyclic peptide, a peptidomimetic, a polyamide, and a macrolactam (e.g., peptidomimetics as per [0056]).
Regarding claims 88 and 92-93, Dower discloses the above, wherein said cleaving agent is selected from the group consisting of an acid, an alkali agent, UV irradiation, and light irradiation (e.g., trifluoroacetic acid can be used to cleave the amide linkage to the bead in Fig. 8, or an oxidizer or reducer can be used to cleave the sulfide linkage in Fig. 3).
Regarding claim 89, Dower discloses the above, wherein said cleaving agent does not cleave said ligand domain from the surface of said immobilized microparticle (e.g., an oxidizer or reducer can be used to cleave the sulfide linkage in Fig. 3 without cleaving the amide linkage for the ligand domain).
Regarding claim 94, Stuelpnagel discloses the above, wherein said ordered array is located within a detection device (e.g., as fiber optic bundle as per Fig. 1-2).
Regarding claim 95, Stuelpnagel discloses the above, wherein said ordered array comprises a density selected from the group consisting of at least 10,000 microparticles per square millimeter, at least 50,000 microparticles per square millimeter, at least 150,000 microparticles per square millimeter, and at least 250,000 microparticles per square millimeter (e.g., as per [0036]).
Regarding claim 96, Stuelpnagel discloses the above, wherein said high throughput biological screening assay is selected from the group consisting of a microarray screen, a fluorescence binding assay, a colorimetric binding assay, and an electrochemical binding assay (e.g., a fluorescence binding assay as per [0212]).
Regarding claim 100, Dower discloses the above, wherein said first functionalized group is an amino group, and said second functionalized groups is a hydroxyl group (e.g., as per Example 3 and depicted in Fig. 8).
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Response to Arguments
The 11/17/2025 remarks argue: not all elements are taught.
Applicant's arguments have been fully considered but they are not persuasive for at least the following reasons.
Specifically, the rejection above has been altered to the extent necessitated by Applicant’s amendments to the claim and now fully address the arguments raised by Applicant in the 11/17/2025 response.
Stuelpnagel et al., Dower et al., and Guillier et al.
Claims 76-86, 88, 92-97, and 100 are rejected under 35 U.S.C. 103 as being unpatentable over Stuelpnagel et al. (U.S. PGPub 2002/0150909 A1, cited in IDS of 06/21/2022) in view of Dower et al. (WO 93/06121, of record) and further in view of Guillier et al. (Chem. Rev., 2000, 100:2091-2157, cited in IDS of 08/13/2025).
Stuelpnagel in view of Dower is relied on as above, however, it is noted that the references are silent on the limitation of said second linker comprises an acyl group, a sulfonamide group, or a photocleavable group, as set forth in claim 97.
Guillier is a review titled “Linkers and Cleavage Strategies in Solid-Phase Organic Synthesis and Combinatorial Chemistry” and discloses a method of creating encoded combinatorial libraries, similar to Stuelpnagel, wherein the encoding tags are attached to the microparticles via photocleavable linkers (e.g., as per pp. 2128-2132), thereby reading on the limitations of claim 97.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use the microparticles and/or linkers of Guillier in the assay methods of Stuelpnagel in view of Dower. One of ordinary skill in the art would have been motivated to do so since Stuelpnagel in view of Dower simply stated that any appropriate beads may be used without much guidance (e.g., as per ¶0049) and Guillier provides an expertly researched assortment of compatible chemistries for the field of combinatorial screening, being the same field as Stuelpnagel and Dower. Further, as per MPEP 2143(I)(A), the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since many of the microparticles and chemistries set forth in Guillier had been successfully used for several decades as of the effective filing date (e.g., Merrifield polystyrene beads were introduced in 1963 as per Guillier at page 2092), and several were available as commercial kits.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684