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 .
Applicant’s reply to the May 08, 2025 Office Action, filed November 04, 2025, is
acknowledged. Applicant previously cancels claims 4, 7, 11-14, 19-32, 34-37, 39-46 and 48-73. Claims 1-3, 5-6, 8-10, 15-18, 33, 38, 47 and 74-76 are currently pending and under examination.
Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is Final.
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 (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 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 8, 10, 15-17, 38 and 74-75 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Ljungars et al. (“Deep Mining of Complex Antibody Phage Pools Generated by Cell Panning Enables Discovery of Rare Antibodies Binding New Targets and Epitopes. Front Pharmacol. 10:847 published July 30, 2019). This is a new rejection as necessitated by amendments.
Regarding claim 1, Ljungars teaches a method of selecting for a polypeptide that selectively binds to a target protein (Abstract). Ljungars teaches contacting a first polypeptide pool comprising a plurality of polypeptides with a first entity that does not comprise said target protein to form a first mixture (Page 3, Left Column, Second—Third Paragraph and Fig. 1). Ljungars teaches removing said first entity from said first mixture, thereby generating a first depleted polypeptide pool (Page 3, Left Column First Paragraph—Right Column, Last Paragraph). Ljungars teaches contacting said first depleted polypeptide pool with a second entity that comprises said target protein at its surface (Page 3, Left Column—Right Column, Last Paragraph, Page 11, Right Column and Figs. 2 and 4 ). Ljungars teaches collecting polypeptides that bind to said second entity, thereby generating a target polypeptide pool (Fig. 2). Ljungars teaches contacting a second polypeptide pool comprising a plurality of polypeptides with the first entity to form a second mixture (Page 3, Left Column—Right Column, Last Paragraph, Page 11, Right Column and Figs. 2-4 ). Ljungars teaches removing the first entity from the second mixture, thereby generating a second depleted polypeptide pool (Page 3, Left Column—Right Column, Last Paragraph, Page 11, Right Column and Figs. 2-4 ). Ljungars teaches contacting said second depleted polypeptide pool with a third entity that does not comprise said target protein and said third entity is the same or different from said first entity and collecting polypeptides that bind to said third entity, thereby generating an off- target polypeptide pool (Page 3, Left Column—Right Column, Last Paragraph, Page 7, Right Column, Last Paragraph—Page 8, Right Column, Last Paragraph, Page 11, Right Column and Figs. 2-4 ). Ljungars teaches identifying at least one polypeptide that is present in said target polypeptide pool and is not present in said off-target polypeptide pool, thereby selecting for a polypeptide that selectively binds to said target protein (Page 16, Left Column Second Paragraph and Figs. 8 and 4). Ljungars teaches said first polypeptide pool and said second polypeptide pool are an antibody library comprising a plurality of antibodies or antibody fragments (Figs 1-2 and 4).
Regarding claim 2, Ljungars teaches performing one or more rounds of (a)-(h), each successive round using a target polypeptide pool generated in (d) as a first polypeptide pool in (a), and using an off-target polypeptide pool generated in (h) as a second polypeptide pool in (e) (Abstract, Page 3, Left Column, Second Paragraph and Page 14, Right Column, First Paragraph).
Regarding claim 8, Ljungars teaches for each successive round of (a)-(h), said first entity, said second entity, and said third entity are of a different type from a preceding round (Abstract, Page 3, Left Column, Second Paragraph—Right Column, Last Paragraph and Page 6, Left Column, Second Paragraph).
Regarding claim 10, Ljungars teaches said first entity comprises a plurality of first entities, said second entity comprises a plurality of second entities, and said third entity comprises a plurality of third entities (Abstract, Page 3, Left Column, Second Paragraph—Right Column, Last Paragraph and Page 6, Left Column, Second Paragraph).
Regarding claim 15, Ljungars teaches said target protein is a cell-surface protein, a membrane-bound protein, or a protein engineered to be expressed at a cell surface (Page 5, Right Column, Last Paragraph).
Regarding claim 16, Ljungars teaches said target protein is a transmembrane protein or an integral membrane protein (Page 3, Left Column, Last Paragraph—Right Column Last Paragraph, Page 15, Left Column, Last Paragraph).
Regarding claim 17, Ljungars teaches the target protein is the transmembrane protein, and said transmembrane protein is a single pass transmembrane protein or a multi-pass transmembrane protein (Page 3, Left Column, Last Paragraph—Right Column Last Paragraph, Page 15, Left Column, Last Paragraph).
Regarding claim 38, Ljungars teaches said first polypeptide pool, said second polypeptide pool, or both comprises at least ten polypeptides (Fig. 1).
Regarding claim 74, Ljungars teaches said sequencing comprises next generation sequencing (Page 3, Right Column, Last Paragraph and Page 11, Left Column—Right Column, Last Paragraph).
Regarding claim 75. Ljungars teaches said first entity comprises a plurality of first cells, said second entity comprises a plurality of second cells, and said third entity comprises a plurality of third cells (Abstract, Page 3, Left Column, Second Paragraph—Right Column, Last Paragraph and Page 6, Left Column, Second Paragraph).
Ljungars teaches each and every claim limitation of claims 1-2, 8, 10, 15-17, 38 and 74-75, therefore Ljungars anticipates claims 1-2, 8, 10, 15-17, 38 and 74-75.
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 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.
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 3 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Ljungars et al. (“Deep Mining of Complex Antibody Phage Pools Generated by Cell Panning Enables Discovery of Rare Antibodies Binding New Targets and Epitopes. Front Pharmacol. 10:847 published July 30, 2019), as applied to claims 1-2, 8, 10, 15-17, 38 and 74-75 above, and in view of Schwartz et al. (U.S. Patent Application Publication US 2012/0258870 A1, published October 11, 2012), Previously cited on the August 07, 2025 Office Action. This is a new rejection as necessitated by amendments.
Regarding claims 3 and 5-6, Ljungars teach the target and off-target polypeptides as discussed above.
Ljungars does not teach or suggest sequencing a polynucleotide tag attached to said at least one polypeptide. Ljungars does not teach or suggest sequencing polynucleotide tags attached to said plurality of target polypeptides and sequencing polynucleotide tags to said plurality of off-target polypeptides. Ljungars does not teach or suggest each of said polynucleotide tags is different for each target polypeptide and for each off-target polypeptide.
Schwartz teaches detecting biological targets and non-target materials of a sample (Abstract and Page 94, [0810]). Schwartz teaches target polypeptides and proteins (Page 9, [0129], Pages 18-19, [0187]). Schwartz teaches using different probes (different barcodes) to detect target sequences and non-target sequences (Page 2, [0014] and [0017], Page 8, [0102], Page 9, [0127], Page 29, [0240] and Examples 7C-11C). Schwartz teaches sequencing the probes (Page 40, [0286]). Shwartz teaches sequencing polynucleotide tags attached to said plurality of target polypeptides and sequencing polynucleotide tags to said plurality of off-target polypeptides (Page 40, [0286] and Examples 7C-11C). Schwartz teaches using these methods with antibody-oligonucleotide conjugates, protein-oligonucleotide conjugates, or peptide-oligonucleotide conjugates, allow for use in diagnostics and/or therapeutic applications (Page 4, [0037]). Schwartz teaches use of unique probes and detectable labels allows for multiplexing as well as automation (Pages 25-26, [0244]-[0225]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Ljungars with the teachings of Schwartz, to sequence uniquely probed target and off-target peptides that are different. Using these unique probes and methods allows for multiplexing as well as automation and use in diagnostics and/or therapeutic applications as taught by Schwartz (Page 4, [0037] and Pages 25-26, [0244]-[0225]).
Claims 9, 18, 33 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Ljungars et al. (“Deep Mining of Complex Antibody Phage Pools Generated by Cell Panning Enables Discovery of Rare Antibodies Binding New Targets and Epitopes. Front Pharmacol. 10:847 published July 30, 2019), as applied to claims 1-2, 8, 10, 15-17, 38 and 74-75 above, and in view of Jones et al. (“Targeting membrane proteins for antibody discovery using phage display”. Scientific Reports 6, 26240, published May 18, 2016), cited on the IDS filed June 28, 2022. This is a new rejection as necessitated by amendments.
Regarding claims 9, 33 and 76, Ljungars teaches each successive round of (a)-(h), said first entity, said second entity, and said third entity as discussed above.
Regarding claim 18, Ljungars teaches said target protein as discussed above.
Ljungars does not teach or suggest said first entity, said second entity, and said third entity are from a different species than from a preceding round or the whole cell of said first entity, said second entity, and said third entity are different cells than a preceding round. Ljungars does not teach or suggest wherein any one of said first entity, said second entity, and said third entity comprises a whole cell. Ljungars does not teach or suggest said target protein is selected from the group consisting of. a ligand-gated ion channel, a voltage-gated ion channel, and a G protein-coupled receptor (GPCR).
Jones teaches whole cell bio-panning and successful isolation of an antibody library for 3 membrane bound proteins (Abstract). Jones teaches using whole cells maintains a native conformation of the protein (Page 2, First Paragraph). Jones teaches the target protein may be a multi-pass membrane protein such as ion gated channels (Page 7, First Paragraph). Jones teaches 4 rounds of selection using biopanning with three different types of entities (cells from different species/types, CHO and HEK cells, Figs. 1-4). Jones teaches alternating host cell lines with each repeated round of panning (Figs. 1-4). Jones teaches that alternating the host cell lines between each round of biopanning greatly improves the specificity and phage pool enrichment (Page 3, Last Paragraph).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Ljungars with the teachings of Jones, using whole cell bio-panning with the target protein being a multi-pass membrane protein such as ion gated channels and using 4 rounds of successive biopanning with alternating host cells lines. Using whole cells allows for maintaining a native conformation of the protein and using alternating cell lines between each round of biopanning greatly improves the specificity and phage pool enrichment as taught by Jones (Page 2, First Paragraph and Page 3, Last Paragraph).
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Ljungars et al. (“Deep Mining of Complex Antibody Phage Pools Generated by Cell Panning Enables Discovery of Rare Antibodies Binding New Targets and Epitopes. Front Pharmacol. 10:847 published July 30, 2019), as applied to claims 1-2, 8, 10, 15-17, 38 and 74-75 above, and in view of Stern et al. (“Cellular-Based Selections Aid Yeast-Display Discovery of Genuine Cell-Binding Ligands: Targeting Oncology Vascular Biomarker CD276”, ACS Combinatorial Science, 21(3), pgs. 207-222, published January 08, 2019), cited on the IDS filed June 28, 2022. This is a new rejection as necessitated by amendments.
Regarding claim 47, Ljungars teaches the target protein as discussed above.
Ljungars does not teach or suggest performing one or more affinity maturation steps on said at least one polypeptide to generate a polypeptide with increased affinity for said target protein.
Stern teaches a method of selecting for a polypeptide that selectively binds to a target protein (Abstract). Stern teaches contacting a first polypeptide pool comprising a plurality of polypeptides with a first entity that does not comprise said target protein to form a first mixture and removing said first entity from said first mixture, thereby generating a first depleted polypeptide pool (Page 208, Right Column, First Two Paragraphs, Page 210, Whole Right Column and Figs. 1-4 and 6-7). Stern teaches contacting said first depleted polypeptide pool with a second entity that comprises said target protein at its surface (Page 208, Right Column, Third Paragraph, Page 215, Bridging Paragraph between Left and Right Column, Page 208, Left Column, Second Paragraph and Figs. 1-4 and 6-7). Stern teaches collecting polypeptides that bind to said second entity, thereby generating a target polypeptide pool (Page 208, Right Column, Third Paragraph, Page 215, Bridging Paragraph between Left and Right Column, Page 208, Left Column, Second Paragraph and Figs. 1-4 and 6-7). Stern teaches performing one or more affinity maturation steps on said at least one polypeptide to generate a polypeptide with increased affinity for said target protein (Abstract). Stern teachings using the disclosed methods allows for identification of more robust ligand selection strategies which can be used for diagnostic and therapeutic benefits (Page 220, Right Column, Fifth Paragraph).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Ljungars with the teachings of Stern, performing one or more affinity maturation steps on said at least one polypeptide to generate a polypeptide with increased affinity for said target protein. Using these methods would allow for identification of more robust ligand selection strategies which can be used for diagnostic and therapeutic benefits as taught by Stern (Page 220, Right Column, Fifth Paragraph).
Response to Arguments
Applicant’s arguments and amendments filed August 25, 2023, with respect to the rejections under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, these rejections have been withdrawn.
However, upon further consideration, new grounds of rejections under U.S.C. § 102 and 103 are made in view of Applicant’s amendments.
As discussed above, newly cited Ljungars discloses methods of selecting for a polypeptide that selectively binds to a target protein. Ljungars discloses contacting a first polypeptide pool comprising a plurality of polypeptides with a first entity that does not comprise said target protein to form a first mixture and removing said first entity from said first mixture, thereby generating a first depleted polypeptide pool. Ljungars discloses contacting said first depleted polypeptide pool with a second entity that comprises said target protein at its surface and collecting polypeptides that bind to said second entity, thereby generating a target polypeptide pool. Ljungars discloses contacting a second polypeptide pool comprising a plurality of polypeptides with the first entity to form a second mixture and removing the first entity from the second mixture, thereby generating a second depleted polypeptide pool. Ljungars discloses contacting said second depleted polypeptide pool with a third entity that does not comprise said target protein and said third entity is the same or different from said first entity and collecting polypeptides that bind to said third entity, thereby generating an off- target polypeptide pool. Ljungars discloses identifying at least one polypeptide that is present in said target polypeptide pool and is not present in said off-target polypeptide pool, thereby selecting for a polypeptide that selectively binds to said target protein. Ljungars discloses said first polypeptide pool and said second polypeptide pool are an antibody library comprising a plurality of antibodies or antibody fragments.
Therefore, for these reasons and those listed above, Ljungars, Ljungars in view of Schwartz, Ljungars in view of Jones and Ljungars in view of Stern are deemed to render the instant invention anticipated/obvious.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 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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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684