DETAILED ACTION
Status of the Claims
Claims 1-16 are currently pending and are examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/12/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, for example, in line 14 of p. 6, line 33 of p. 7, line 21 of p. 20, and line 17 of p. 31. The foregoing analysis should not to be deemed exhaustive, as there may be other embedded hyperlinks as well. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01.
Objection to the Drawings
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specifically, Fig. 5A and 5B each show nucleic acid sequences that are not labeled with corresponding SEQ ID NOs, either in the drawing or in the Brief Description of the Drawings in the specification.
Claim Interpretation
As per MPEP § 2111 and § 2111.01, during patent examination, the pending claims must be interpreted as broadly as their terms reasonably allow while being consistent with the specification. The words of a claim must be given their ‘plain meaning’ unless such meaning is inconsistent with the specification, wherein ‘plain meaning’ of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. Because applicant has the opportunity to amend the claims during prosecution, giving a claim its broadest reasonable interpretation will reduce the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Yamamoto, 740 F.2d 1569, 1571 (Fed. Cir. 1984)
Below are notes made by the examiner regarding claim interpretation of the most recent set of claims. Applicant is respectfully invited to comment on or dispute any of these statements.
The term “binder” is defined in para [0153] of the published application (U.S. PGPub 2025/0129362 A1), which states (in part): “A ‘binder’ in accordance with the present invention is a binding molecule, representing a specific binding partner for another molecule.” This reasonable encompasses antibodies and fragments thereof (e.g., svFc, Fab, nanobodies, F(ab’)2, VHH domains, single-domain antibodies, bispecific antibodies, etc.), nucleic acids and aptamers made thereof, receptors, ligands, small molecules, and generally any moiety which can specifically bind to a target molecule.
Claim 13 recites “[a] binder identified from the library according to claim 10” and is therefore a product-by-process claim. Note that as per MPEP § 2113, “product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps”. The same MPEP section states that “‘even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.’ In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). In the present case, the process steps (as per claim 10) are expressing recombinant DNA in eukaryotic cells and selecting for a binder against a target. Therefore, claim 13 reasonably encompasses binders (e.g., antibodies and/or fragments thereof, aptamers, etc.) that can be expressed in eukaryotic cells.
Claim Rejections - 35 USC § 112(b) -- Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-5 and 10-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 4, 10-11, and 14-15 each recite the terms “preferably”, “more preferably”, and/or “most preferably”. As per MPEP 2173.05(c)-(d), “[i]f stated in a single claim, examples and preferences lead to confusion over the intended scope of the claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made.”
Claims 5 and 12-13 depend from claims 4 and 10, and are therefore similarly rejected.
In the interest of compact prosecution and for the application of prior art below, the terms “preferably”, “more preferably”, and “most preferably” will be interpreted as “optionally”.
As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Claim Rejections – 35 U.S.C. 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
Ng et al.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ng et al. (WO 2019/126634, cited in IDS of 03/12/2025).
Regarding claim 1, Ng discloses a method for identifying a locus in a genome of a eukaryotic cell, said locus being a candidate for insertion of binder sequences, said method comprising:
providing a landing pad sequence (e.g., as per Fig. 2A);
introducing the landing pad sequence into the eukaryotic cell (e.g., as per Fig. 1);
randomly integrating the landing pad sequence into the genome of the eukaryotic cell via transposon-mediated integration (e.g., as per Example 1);
selecting a clone having a landing pad sequence integrated into its genome (e.g., as per Example 1).
Regarding claim 2, Ng discloses the above method, comprising the further steps of screening for single-copy integration, and identifying the locus (e.g., as per Example 1, such as the finding of “a single GFP landing pad was inserted into the CHO genome” as per p. 102).
Claim Rejections – 35 U.S.C. 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 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.
Ng et al. and Parthiban et al.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Ng et al. (WO 2019/126634, cited in IDS of 03/12/2025) in view of Parthiban et al. (mAbs, 2019, 11:5, 884-898, cited in IDS of 03/12/2025).
Ng is relied on as above, however, the reference is silent as to the limitations of integrating a donor DNA sequence comprising one or more transgenes encoding a binder at the landing pad sequence and screening for integration of the donor DNA, wherein the landing pad sequence comprises a recognition sequence for a site-specific nuclease, as set forth in claims 3-13.
Regarding claim 3, Parthiban discloses integrating a donor DNA sequence comprising one or more transgenes encoding a binder at the landing pad sequence and screening for integration of the donor DNA (e.g., as per the Cell culture and transfection section on p. 896).
Regarding claim 4, Parthiban discloses the above, wherein the landing pad sequence comprises a recognition sequence for a site-specific nuclease (e.g., as per Fig. 1a).
Regarding claim 5, Parthiban discloses the above method, wherein the step of integrating the donor DNA into the cells comprises providing a site-specific nuclease within the cells, wherein the nuclease cleaves the recognition sequence comprised in the landing pad (e.g., as per Fig. 1a).
Regarding claim 6, Parthiban discloses the above method, wherein the step of screening for integration of the donor DNA comprises screening for display of the one or more binders encoded by the donor DNA (e.g., as per Fig. 3).
Regarding claim 7, Parthiban discloses the above method, wherein the donor DNA further comprises homology arms to increase integration efficiency (e.g., as per the Vector construction section on pp. 894-895).
Regarding claim 8, Parthiban discloses the above method, wherein the landing pad sequence and/or the donor DNA sequence comprise a selectable marker (e.g., blasticidin as per Fig. 1).
Regarding claim 9, Parthiban discloses the above method, wherein the locus is used for building a library of eukaryotic cell clones containing DNA encoding a diverse repertoire of binders (e.g., as per the Abstract).
Regarding claim 10, Parthiban discloses an in vitro library of eukaryotic cell clones that express a diverse repertoire of at least 10^3, 10^4, 10^5, 10^6, 10^7, 10^8 or 10^9 different binders, each cell containing recombinant DNA wherein donor DNA encoding a binder or subunit of a binder is integrated in at least a first and/or a second fixed locus in the cellular DNA, said locus or loci being identified by the method according to claim 1 (e.g., “[w]e have created mammalian cell libraries of up to 10 million clones displaying a repertoire of IgG-formatted antibodies on the cell surface” as per the Abstract).
Regarding claim 11, Parthiban discloses the in vitro library of eukaryotic cell clones according to claim 10, wherein the locus or loci are in an intron of the gene (e.g., “Antibody genes were integrated into the first intron of the protein phosphatase 1, regulatory subunit 12C (PPP1R12C) gene” as per the Vector construction section on pp. 894-895).
Regarding claim 13, Parthiban discloses a binder identified from the library according to claim 10 (e.g., anti-PD-1 antibodies as per the Functional activity of affinity matured anti-PD-1 antibodies section on pp. 892-893).
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 identify safe harbor integration sites as per Ng in the mammalian cell display method of Parthiban. One of ordinary skill in the art would have been motivated to do so since Ng’s discovered genomic loci were shown to support stable antibody integration for the library constructed by Parthiban. Furthermore, 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 landing pad discovery and mammalian cell display were well known in the art, as per Ng and Parthiban, 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 Ng had already identified genomic loci suitable for stable antibody integration and Parthiban had detailed the means to produce a mammalian cell display library ready for inserting into the landing pad of Ng.
Subject Matter Free of the Prior Art
In the interest of compact prosecution, it is noted that the subject matter of claims 14-16 was searched and found to be free of the art. However, as noted above, the claims have been rejected under 35 U.S.C. 112(b) as being indefinite as currently written.
Conclusion
No claims are allowed.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
Prosecution Insights