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 .
Claims 1, 3, 5-8,12, 16-19, 21-34, 37-38, 42-45 and 47-49 are pending. Claims 22-34, 37-38, 42-45 and 47-49 are withdrawn. Claims 1, 3, 5-8,12, 16-19 and 21 are under examination.
Information Disclosure Statement
The information disclosure statements filed 6/24/24 and 5/23/25 have been considered and initialed copies are enclosed.
Election/Restrictions
Applicant’s election without traverse of claims 1, 3, 5-8, 12, 16-19 and 21 in the reply filed on 9/29/25 is acknowledged.
Claims 22-34, 37-38, 42-45 and 47-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected claims, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/29/25.
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 5, 6 and 21 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 and dependent claim 6 recites the limitation.“anti-CD117 binding moiety” which lacks antecedent basis because claim 1 does not recite the limitation
Claim 21 recites the limitation "bispecific antibody or a bispecific antigen binding portion thereof of claim 1" in line 2. There is insufficient antecedent basis for this limitation in the claim because claim 1 only recites “bispecific binding polypeptide”.
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)(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(s) 1, 3 and 21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uhlin et al. US 2017/0298148 10/19/2017 cited in IDS.
Claim 1: Uhlin et al disclose a bispecific antibody comprising an antibody that binds to CD117 expressed on hematopoietic stem or progenitor cells; and a second antibody that binds CD3 expressed on a T cell. See abstract and paragraph 10.
Paragraph 10 discloses:
Another object of the invention is a monoclonal antibody directed to a target antigen present specifically on, or a marker for, HSCs, or present on, or a marker for, both a malignant cell, such as cancer cell, and HSC. In one aspect, the target can be CD34. In another aspect, the target can be CD133. In a further aspect, the target further includes, but is not limited to, CD59.sup.+, Thy1/CD90.sup.+ or C-kit/CD117, which, just as CD34 and CD133, target HSCs but not most other hematopoietic cells since they are present almost solely on stem cells. The multi- or bi-specific antibodies of the invention can be directed against at least one activating molecule on effector cells, e.g. T cells, NK cells or macrophages, and one marker specific for HSCs or shared by both tumor cells and HSCs. The activating molecules can include, but is not limited to, CD3, TCR, CD16, NK receptors that include, but are not limited to, NKG2D, NKp44, NKp46, and/or NKp30, and/or DNAM, and/or other activating molecules. In one aspect, the antibody can be a BiTE targeting CD3 and CD34. In another aspect the antibody can be a BiTE targeting CD3 and CD133.
Claim 3: Uhlin et al disclose the anti-CD117 antibody comprises an anti-CD117 single chain variable fragment (scFv) and the anti-CD3 antibody comprises an anti-CD3 scFv. See paragraph 37 disclosing there are many types and ways to manufacture multi- and bi-specific monoclonal antibodies, one of the most promising formats being a bi-specific T cell engager (BiTE). BiTEs are fusion proteins consisting of two single-chain variable fragments (scFvs) of different antibodies. In a further embodiment, the BiTE can be directed against CD3 and C-kit/CD117.
Claim 21: Uhlin et al disclose a pharmaceutical composition comprising a therapeutically effective amount of the bispecific antibody. See paragraphs 324-359.
See entirety of Uhlin et al for context of the cited portions.
Claim Rejections - 35 USC § 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 (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 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 1, 5, 7 and 12 is/are rejected under 35 U.S.C. 103 as being obvious over Uhlin et al. US 2017/0298148 10/19/2017 cited in IDS in view of Pearse et al. US 2019/0153114 5/23/2019.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Uhlin et al disclose a bispecific antibody comprising an antibody that binds to CD117 expressed on hematopoietic stem or progenitor cells; and a second antibody that binds CD3 expressed on a T cell. See abstract and paragraph 10.
Paragraph 10 discloses:
Another object of the invention is a monoclonal antibody directed to a target antigen present specifically on, or a marker for, HSCs, or present on, or a marker for, both a malignant cell, such as cancer cell, and HSC. In one aspect, the target can be CD34. In another aspect, the target can be CD133. In a further aspect, the target further includes, but is not limited to, CD59.sup.+, Thy1/CD90.sup.+ or C-kit/CD117, which, just as CD34 and CD133, target HSCs but not most other hematopoietic cells since they are present almost solely on stem cells. The multi- or bi-specific antibodies of the invention can be directed against at least one activating molecule on effector cells, e.g. T cells, NK cells or macrophages, and one marker specific for HSCs or shared by both tumor cells and HSCs. The activating molecules can include, but is not limited to, CD3, TCR, CD16, NK receptors that include, but are not limited to, NKG2D, NKp44, NKp46, and/or NKp30, and/or DNAM, and/or other activating molecules. In one aspect, the antibody can be a BiTE targeting CD3 and CD34. In another aspect the antibody can be a BiTE targeting CD3 and CD133.
Uhlin et al disclose the anti-CD117 antibody comprises an anti-CD117 single chain variable fragment (scFv) and the anti-CD3 antibody comprises an anti-CD3 scFv. See paragraph 37 disclosing there are many types and ways to manufacture multi- and bi-specific monoclonal antibodies, one of the most promising formats being a bi-specific T cell engager (BiTE). BiTEs are fusion proteins consisting of two single-chain variable fragments (scFvs) of different antibodies. In a further embodiment, the BiTE can be directed against CD3 and C-kit/CD117.
Uhlin et al disclose a pharmaceutical composition comprising a therapeutically effective amount of the bispecific antibody. See paragraphs 324-359.
See entirety of Uhlin et al for context of the cited portions.
Uhlin et al does not disclose that the anti-CD117 binding moiety comprises the heavy and light chain CDRS and the heavy chain and light chain as set forth in claims 5, 7 and 12.
Pearse et al disclose a bispecific antibody comprising an antibody that binds to CD117 expressed on hematopoietic stem or progenitor cells; and a second antibody that binds to another cell. See paragraph 143, 232-234, 247, 248, 374 and 375: For instance, one of the binding specificities can be directed towards a hematopoietic stem cell surface antigen, CD117 (e.g., GNNK+ CD117), and the other can specifically bind a different hematopoietic stem cell surface antigen or another cell surface protein, such as a receptor or receptor subunit involved in a signal transduction pathway that potentiates cell growth, among others.
Pearse et al disclose the CD117 antibody comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 13 (SEQ ID NO: 143)and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 14 (SEQ ID NO: 144). SEQ ID NO: 143 comprises the CDRS having the amino acid sequence SEQ ID NO: 7-12.
Pearse et al disclose the CD117 antibody comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 27 (SEQ ID NO: 9)and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 28 (SEQ ID NO: 10). SEQ ID NO: 143 comprises the CDRS having the amino acid sequence SEQ ID NO: 21-26.
Pearse et al disclose that the bispecific antibody or antigen binding portion thereof comprises an Fc region that comprises an amino acid substitution relative to a wild-type Fc region at position L234 and/or L235 (paragraph 452, 457) and/or H435 (paragraph 315 and 458.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the bispecific antibody of Uhlin et al and utilize the anti-CD117 antibody of Pearse et al as the anti-CD117 antibody or antigen binding fragment thereof of Uhlin et al, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that the bispecific antibody of Uhlin et al requires an anti-CD117 antibody and the anti-CD117 antibody well described by Pearse et al could be used in said bispecific antibody of Uhlin et al since this would allow creation of the BiTEs that targets HSC stem cells and CD3 T cells.
Claims 6 and 8 is/are rejected under 35 U.S.C. 103 as being obvious over Uhlin et al. US 2017/0298148 10/19/2017 cited in IDS and Pearse et al. US 2019/0153114 5/23/2019 cited in IDS as applied to claims 1, 5, 7 and 12 above, further in view of Raum et al. US20170029502 2/2/2017 cited in IDS.
The combination of Uhlin et al and Pearse et al set forth above does not disclose the CD3 binding region comprises an amino acid sequence as set forth in SEQ ID NO; 37 and an amino acid sequence as set forth in SEQ ID NO: 38.
Raum et al discloses bispecific and multi-scFv antibody constructs (abstract - "The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human MSLN on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell."; para [0099] - “As described herein above, the invention provides a preferred embodiment wherein the antibody construct is in a format selected from the group consisting of (scFv)2, scFv-single domain mAb, diabodies and oligomers of any of the those formats."), and a CD3 binding construct comprising SEQ ID NOs: 37-38 (para [0173] - "Also preferred in connection with the antibody construct of the present invention is a second binding domain which binds to human CD3 on the surface of a T cell comprising a VL region as depicted in SEQ ID NO: 102 and a VH region as depicted in SEQ 1D NO: 101.".
SEQ ID NO: 101 of Raum et al exhibits 100% identity with SEQ ID NO: 37 of the instant application and SEQ ID NO: 102 of Raum et al exhibits 100% identity with SEQ ID NO: 38 of the instant application.
It would have been obvious to one of ordinary skill in the art as of the effective filing date to have modified the bispecific antibody of the combination of Uhlin et al and Pearse et al to utilize the described anti-CD3 binding region of Raum et al, thus resulting in the instantly claimed bispecific antibody with a reasonable expectation of success.
The motivation to do so is that this would have allowed creation of bispecific antibodies, such as BiTEs, using the anti-CD117 and anti-CD3 binding regions of the combination of Uhlin et al and Pearse et al.
Claims 6 and 8 is/are rejected under 35 U.S.C. 103 as being obvious over Uhlin et al. US 2017/0298148 10/19/2017 cited in IDS and Pearse et al. US 2019/0153114 5/23/2019 cited in IDS as applied to claims 1, 5, 7 and 12 above, further in view of Chen et al. 10,174,124 1/8/2019.
The combination of Uhlin et al and Pearse et al set forth above does not disclose the CD3 binding region comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 41 and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 45.
Chen et al discloses a CD3 antibody comprises a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 41 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 45.
SEQ ID NO: 184 of Chen et al exhibits 100% identity with SEQ ID NO: 41 of the instant application and SEQ ID NO: 185 of Chen et al exhibits 100% identity with SEQ ID NO: 45 of the instant application. See column 1 under summary to page 2 first paragraph. Chen et al disclose that the antibody can be used in a bispecific antibody. See column 16 lines 43-46 and claim 2.
It would have been obvious to one of ordinary skill in the art as of the effective filing date to have modified the bispecific antibody of the combination of Uhlin et al and Pearse et al to utilize the described anti-CD3 binding region of Chen et al, thus resulting in the instantly claimed bispecific antibody with a reasonable expectation of success.
The motivation to do so is that this would have allowed creation of bispecific antibodies, such as BiTEs, using the anti-CD117 and anti-CD3 binding regions of the combination of Uhlin et al and Pearse et al.
Claims 16-19 is/are rejected under 35 U.S.C. 103 as being obvious over Uhlin et al. US 2017/0298148 10/19/2017 cited in IDS and Pearse et al. US 2019/0153114 5/23/2019 cited in IDS as applied to claims 1, 5, 7 and 12 above, further in view of Maynard et al. US 2018/0118817 5/3/2018.
The combination of Uhlin et al and Pearse et al does not disclose the bispecific antibody, or a bispecific antigen-binding portion thereof wherein the Fc region comprises a first CH3 region comprising amino acid substitutions at positions T366, L368, and Y407 (EU index), and a second CH3 region comprising an amino acid substitution at position T366 (EU index).
Maynard et al disclose the amino acid sequence of the human IgG1 hinge-Fc region containing a hinge region, CH2 domain and CH3 domain with Kabat numbering shown. See figure 1 and paragraph 19. Maynard et al disclose making bispecific antibodies comprising heavy chains that are engineered to heterodimerize through the knobs-into-holes technology. Maynard et al disclose the mutations are introduced into the CH3 domains of the heavy chain derived from humanized antibodies to modify the contact interface between two heavy chains. See paragraph 59, 61, 62 and 154.
Maynard et al disclose mutating immunoglobulin heavy chain CH3 domains wherein the mutations comprise mutations at T366, L368, and Y407 numbered according to the EU index in Kabat. The mutations are T366Y, T366S, T366W, L368A, Y407S, Y407T and Y407V. See paragraph figure 1, 19, 61-62.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have mutated the CH3 domains of the anti-CD117 and anti-CD3 antibodies of the combination of Uhlin et al and Pearse et al as taught by Maynard et al, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Maynard et al as set forth above disclose that engineering the amino acid sequence of the human IgG1 hinge-Fc region in the human CH3 domain at T366, L368, and Y407 numbered according to the EU index in Kabat modifies the interface between two heavy chains so that they heterodimerize through the knobs-into-holes technology to form the bispecific antibodies. See Maynard et al at paragraph 61-63 and example 2 disclosing the knob and hole mutations that are used to make the bispecific antibody.
Status of Claims
Claims 22-34, 37-38, 42-45 and 47-49 are withdrawn. Claims 1, 3, 5-8,12, 16-19 and 21 are rejected.
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/OLUWATOSIN A OGUNBIYI/Primary Examiner, Art Unit 1645