, 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 .
Status of Claims
Claims 1-4, 9, 13, 15, 18, 19, 22, 24, 26, 32-33, 46, 50, 55, 57, and 61-62 are pending.
Priority
Claims 1-4, 9, 13, 15, 18, 19, 22, 24, 26, 32-33, 46, 50, 55, 57, and 61-62 are CIP of PCT/CN 2024/070020 filed on January 2, 2024.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on August 29, 2025, was filed before the mailing of the First Office Action on September 5, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Drawings
The drawings are objected to because:
Fig. 1 notation is not legible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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 32 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 32 recites “A non-human animal whose genome comprises…immunoglobulin locus of a non-human animal”. There is improper antecedent basis for the second recitation of “non-human animal”. The second recitation should read “[[a]] the non-human animal”.
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.
Claim 1-4, 9, 13, 15, 18-19, 22, 32-33, 46, 50, and 61-62 are rejected under 35 U.S.C. §102(a)(1) as being anticipated by Bradley et al. [US 11564380 B2, 2023].
Regarding claim 1, Bradley et al. teaches a method for preparing a non-human animal [¶ 0003], the method comprising operably linking a human immunoglobulin variable region downstream [¶ 0047, 0114] of an immunoglobulin locus of the non-human animal [¶ 0114].
Regarding claim 2, Bradley et al. teaches the method of claim 1, comprising operably linking a human immunoglobulin heavy chain variable region gene downstream of an immunoglobulin heavy chain locus of the non-human animal, or comprising operably linking a human immunoglobulin light chain variable region gene downstream of a light chain locus of the non-human animal [¶ 0139].
Regarding claim 3, Bradley et al. teaches the method according to claim 2, comprising operably linking genes of one or more human heavy chain variable V regions, human heavy chain variable D regions or human heavy chain variable J regions, or fragments thereof downstream of the heavy chain constant region locus of the non-human animal; or comprising operably linking the genes of one or more human light chain variable V or J regions, or fragments thereof downstream of a light chain constant region locus of the non-human animal [¶ 0144].
Regarding claim 4, Bradley et al. teaches the method of claim 3, wherein the genes of the more human heavy chain variable V regions, human heavy chain variable D regions or human heavy variable J regions, or fragments thereof are directly linked, or wherein the genes of one or more human light chain variable V regions or J regions, or fragments thereof are directly linked [See Fig. 8 where the FRT sites do not preclude the human variable V, D, and J regions from being directly linked, as Bradley et al. depicts the human variable region genes arranged adjacent to one another with only FRT recombination sites positioned between the respective regions].
Regarding claim 9, Bradley et al. teaches the method according to claim 2, wherein the integrity of the endogenous immunoglobulin variable region genome of the non-human animal is not changed [¶ 0048].
Regarding claim 13, Bradley et al. teaches the method according to claim 2, whereof the non-human animal does not express the endogenous immunoglobulin variable region, and/or wherein the endogenous immunoglobulin variable region genes of the non-human animal do not express functional proteins [¶ 0114].
Regarding claim 15, Bradley et al. teaches the method according to claim 2, comprising allowing the transcription direction of the human immunoglobulin variable region gene to be opposite to that of the endogenous immunoglobulin variable region gene, and/or comprising allowing the transcription direction of the immunoglobulin constant region gene of the non-human animal to be opposite to that of the endogenous immunoglobulin variable region gene [¶ 0171].
Regarding claim 18, Bradley et al. teaches the method according to claim 2, wherein a heavy chain constant region gene of the non-human animal is contained between the human immunoglobulin heavy chain variable region gene and the endogenous immunoglobulin heavy chain variable region gene of the non-human animal, and/or wherein a light chain constant region gene of the non-human animal is contained between the immunoglobulin light chain variable region gene and the endogenous immunoglobulin light chain variable region gene of the non-human animal [¶ 0051].
Regarding claim 19, Bradley et al. teaches the method according to claim 2, wherein a distance between the human immunoglobulin heavy chain variable region gene and the endogenous immunoglobulin heavy chain variable region gene of the non-human animal is 169 Kbp-240 Kbp, and/or wherein a distance between the human immunoglobulin light chain variable region gene and the endogenous immunoglobulin light chain variable region gene of the non-human animal is 4 Kbp-42 Kbp [¶ 0140].
Regarding claim 22, Bradley et al. teaches the method according to claim 2, whereof the non-human animal is a rodent [¶ 0010].
Regarding claim 32, Bradley et al. teaches a non-human animal whose genome comprises a human immunoglobulin variable region gene operably linked downstream of the immunoglobulin locus of a non-human animal [¶ 0003, 0047, and 0114].
Regarding claim 33, Bradley et al. teaches the non-human animal according to claim 32, comprising a human immunoglobulin heavy chain variable region gene operably linked downstream of a heavy chain locus of the non-human animal, and/or comprising a human immunoglobulin light chain variable region gene operably linked downstream of a light chain locus of the non-human animal [¶ 0139].
Regarding claim 46, Bradley et al. teaches the non-human animal according to claim 33, wherein the transcription direction of the human immunoglobulin variable region gene of the non-human animal genome is opposite to that of the endogenous immunoglobulin variable region gene [¶ 0171].
Regarding claim 50, Bradley et al. teaches the non-human animal according to claim 33, wherein a distance between the human immunoglobulin heavy chain variable region gene and the endogenous immunoglobulin heavy chain variable region gene is 169 Kpb-240 Kbp, and/or wherein a distance between the human immunoglobulin light chain variable region gene and the endogenous immunoglobulin light chain variable region gene of the non-human animal is 4 Kbp-42 Kbp [¶ 0140].
Regarding claim 61, Bradley et al. teaches a non-human animal cell, wherein the genome of the non-human animal cell comprises human immunoglobulin variable gene downstream of the immunoglobulin locus [¶ 0003, 0047, and 0114].
Regarding claim 62, Bradley et al. teaches a method for preparing an antibody specifically binding to an antigen, the method comprising immunizing the non-human animal according to claim 33 with the antigen [¶ 0003, 0026, 0027, and 0105].
Claims Free of the Art
Claims 24, 26, 55, and 57 are free of the art. Bradley et al. teaches insertion of human immunoglobulin light chain variable region DNA into or near endogenous mouse immunoglobulin light chain locus. Martinez-Jean et al. discloses the organization of the mouse IGK locus, including IGKV, IGKJ, and IGKC gene segments. However, neither Bradley et al. or Martinez-Jean et al., alone or in combination, teach inserting a human immunoglobulin light chain variable region between the IGKC and RPIA genes at the claimed chromosomal location [Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) genes, Experimental and Clinical Immunogenetics, 2001]. Although Bradley discloses a specific range of positions on chromosome 6, the claimed location still differs by roughly 31,533 bp downstream of the disclosed positions in Bradley et al. [See ¶ 0049]. Based on this, the examiner finds that the disclosures in Bradley et al. and Martinez-Jean et al. would not provide sufficient motivation for a person skill in the art to choose the claimed chromosomal positions.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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