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 .
DETAILED ACTION
The preliminary amendment filed April 14, 2025, is acknowledged and has been entered. Claims 7, 14, 22-33 and 35 have been canceled. Claim 6 has been amended.
Claims 1-6, 8-13, 15-21 and 34 are pending in the application and are under examination.
Information Disclosure Statement
The information disclosure statement has been considered.
Claim Rejections-35 U.S.C. § 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 4 and 8 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.
Claim 4 is indefinite in the recitation of “[t]he T-BiAb of claim 1, wherein at least one of the copies of the amino acid sequence GGGGS (SEQ ID NO: 6)” because claim 1 does not recite the amino acid sequence GGGGS. Therefore, the recitation lacks proper antecedent basis and it cannot be determined which (if any) tumor-associated antigen is being referred to.
Accordingly, the metes and bounds of the claim cannot be properly determined and the invention is not set forth with the clarity and particularity necessary to satisfy the requirement set forth 35 U.S.C. 112, second paragraph, so as permit the skilled artisan to know or determine infringing subject matter.
Claim 8 is indefinite in the recitation of “[t]he T-BiAb of claim 1, wherein the tumor-associated antigen” because claim 1 does not recite a tumor-associated antigen. Therefore, the recitation lacks proper antecedent basis and it cannot be determined which (if any) tumor-associated antigen is being referred to.
Accordingly, the metes and bounds of the claim cannot be properly determined and the invention is not set forth with the clarity and particularity necessary to satisfy the requirement set forth 35 U.S.C. 112, second paragraph, so as permit the skilled artisan to know or determine infringing subject matter.
Claim Rejections - 35 USC § 102
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 1-3, 5-6, 9-11, 15-19 and 34 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Santich et al (WO 2020/113164 A1).
With respect to claims 1-3 and 5, Santich discloses in Figure 1 a tetravalent bispecific antibody (T-BiAb) comprising a first binding moiety and a second binding moiety, wherein the first binding moiety is a single chain variable fragment (scFv) and the second binding moiety is a monoclonal antibody, and further wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are directly linked as a single chain to the second binding moiety at the C-terminus of the light chain sequence of the second binding moiety wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are linked to each other as a single polypeptide chain (scFv) wherein the variable domains of the scFv (and are linked together via a flexible peptide linker comprising the amino acid sequence (GGGGS)6 (see alsoFigures, and pages 6-11 and 130-139 and claims) with the structure:
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With respect to claim 6, Santich et al discloses that the scFv can bind to CD3 (see pages 29-30 and 57). With respect to claims 9 and 34, Santich et al discloses T cells with such a T-BiAb bound (i.e., armed) in a composition that would necessarily comprise a pharmaceutically acceptable carrier such as water. (see Figure 12 and pages 35 and 239-240).
With respect to claims 10-11 and 15-19, Santich et al discloses that such a T-BiAb that binds to CD3 and a tumor antigen, such as HER2, can be used in methods to treat cancer by contacting the cancer, such as breast cancer, or to activate T cells by contacting the cancer or T cells derived from PBMCs with such a T-BiAb (see Figures, pages 33-34, 42, 220-221, 238-240 and claims 35-38).
Therefore, Santich et al is deemed to anticipate the instant claims absent a showing otherwise.
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 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.
Claims 9-11, 15-21 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2017/040324 A1) and Santich et al (WO 2020/113164 A1)
June et al discloses T cells comprising chimeric antigen receptors with a bispecific antibody bound (i.e., armed) in a composition comprising a pharmaceutically acceptable carrier (see pages 2-3). June et al discloses methods of stimulating or activating T cells by contacting T cells with CD3 and CD28 antibodies and then converting the T cells to a CAR T cell and arming it with a bispecific antibody that binds CD3 and a HER2 (see pages 54 and 62-64). June et al discloses methods of administering the armed CAR T cells in an effective amount to treat a cancer, such as breast cancer (see abstract and pages 3, 55-58 and 69-70). June et al discloses “The present invention should not be construed to be limited to any particular bispecific antibody. Rather, any bispecific antibody is useful in the present invention” (see page 29).
June et al does not disclose a bispecific antibody with the instant structure of claim 1.
Santich discloses in Figure 1 a tetravalent bispecific antibody (T-BiAb) comprising a first binding moiety and a second binding moiety, wherein the first binding moiety is a single chain variable fragment (scFv) and the second binding moiety is a monoclonal antibody, and further wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are directly linked as a single chain to the second binding moiety at the C-terminus of the light chain sequence of the second binding moiety wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are linked to each other as a single polypeptide chain (scFv) wherein the variable domains of the scFv (and are linked together via a flexible peptide linker comprising the amino acid sequence (GGGGS)6 (see also Figures, and pages 6-11 and 130-139 and claims) with the structure:
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Santich et al discloses that the scFv can bind to CD3 (see pages 29-30 and 57). With respect to claims 9 and 34, Santich et al discloses T cells with such a T-BiAb bound (i.e., armed) in a composition that would necessarily comprise a pharmaceutically acceptable carrier such as water (see Figure 12 and pages 35 and 239-240).
Santich et al discloses that such a T-BiAb that binds to CD3 and a tumor antigen, such as HER2, can be used in methods to treat cancer by contacting the cancer, such as breast cancer, or to activate T cells by contacting the cancer or T cells derived from PBMCs with such a T-BiAb (see Figures, pages 33-34, 42, 220-221, 238-240 and claims 35-38). Santich et al discloses that a bispecific CD3/CD28 antibody simulates or activated T cells (see page 245).
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art, at the time of the invention, to have predictably substituted the bispecific antibody species of Santich et al, for the generic bispecific antibody of June et al because June et al disclose that “any bispecific antibody is useful in the present invention”. Accordingly, arming the CAR T cells of June et al with a CD3/HER2 antibody of Santich et al would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results because one of skill in the art reading June et al would have recognized that the tetravalent, bispecific antibody of Santich et al which was taught to be useful in targeting T cells to cancer and activating them to treat cancer would also be predictably useful in the compositions and methods of June which disclose using generic bispecific antibodies for similar uses in targeting and activating CAR T cells.
Similarly, with respect to the instantly claimed methods, as CD3 and CD28 antibodies and CD3 and tumor antigen antibodies can be used to activate T cells and treat cancer as evidenced by June et al and Santich et al, one of skill in the art would have also been motivated to use the bispecific antibody species of Santich et al in methods of activating T cells and treating cancer as claimed again because June et al disclose that “any bispecific antibody is useful in the present invention”. Here Santich evidences that their bispecific antibody format predictably binds to both antigens, so that combining a CD3 and CD28 antibody into the Santich antibody format to activate T cells would be expected to predictably result in activated T cells that could then be converted into CAR T cells. Furthermore, then using a CD3 and HER2 antibody in the Santich antibody format to further activate the T cells that are administered to treat cancer would also be expected to give a predicable result because such a bispecific antibody was taught to treat cancer by targeting and activating T cell cytotoxicity towards the cancer cells such that there was a reasonable expectation of success. Furthermore, activating and arming CART T cells ex vivo with such antibodies and then administering the CAR T cells would have the advantage of increasing the number of activated T cells in the patient to better treat the patient.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a showing otherwise.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US 2012/0076786 A1, IDS) as evidenced by Bhattacharya et al (Clin Immunology, 153(1):187-198, 2014), Liu et al (Heart Fail Rev, 21(723-736, 2016) and Santich et al (WO 2020/113164 A1)
Lee et al discloses methods of administering to subjects effective amounts of a bispecific antibody made via chemical conjugation or via recombinant genetic engineering that binds to CD34 or CD45 and myosin light chain that can be armed with stem cells by intravenous fusion (see pages 2-3, 6 and 7). While Lee et al does not disclose that intravenous administration of a bispecific antibody contacts β-cells, as evidenced by Bhattacharya et al bispecific antibodies administered by intravenous fusion do contact β-cells in vivo (see Figure 3). Lee et al discloses that their methods treat injured cardiac tissue by targeting stem cells to the injury and that using bispecific antibody targeting has the advantage of overcoming the downsides related to intramyocardial injection or intracoronary delivery of stem cells (see abstract and page 1).
Liu et al discloses that diabetic cardiomyopathy (DCM) occurs in diabetic patients and that stem cell therapy generally exerts helpful effect on DCM (see abstract and pages 723 and 729). Liu et al discloses that the stem cells can be administered by intramyocardial (IM) or intravenous (IV) injection which both have downsides (see page 730).
Lee et al does not disclose a bispecific antibody with the instant structure of claim 1.
Santich discloses in Figure 1 a tetravalent bispecific antibody (T-BiAb) comprising a first binding moiety and a second binding moiety, wherein the first binding moiety is a single chain variable fragment (scFv) and the second binding moiety is a monoclonal antibody, and further wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are directly linked as a single chain to the second binding moiety at the C-terminus of the light chain sequence of the second binding moiety wherein the variable light (VL) and variable heavy (VH) chains of the first binding moiety are linked to each other as a single polypeptide chain (scFv) wherein the variable domains of the scFv (and are linked together via a flexible peptide linker comprising the amino acid sequence (GGGGS)6 (see also Figures, and pages 6-11 and 130-139 and claims) with the structure:
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Santich et al discloses that one antigen the bispecific antibody can bind is CD45 and that the antibodies of the invention can be useful in treating diabetes (see page 31 and 210).
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art, at the time of the invention, to administer a tetravalent bispecific antibody (T-BiAb) of Santich et al that binds to CD45 or CD34 and myosin light chain or to administer stem cells armed with a tetravalent bispecific antibody (T-BiAb) of Santich et al that binds to CD45 or CD34 and myosin light chain to diabetic patients because such an antibody would have the advantage of targeting the stem cells repair cardiac tissue. Notably, the art recognized that there were disadvantages in administering stem cells by themselves, so administering a tetravalent bispecific antibody (T-BiAb) of Santich et al that binds to CD45 or CD34 and myosin light chain would have the advantage of targeting a patient’s stem cells to repair cardiac tissue and administering stem cells armed with a tetravalent bispecific antibody (T-BiAb) of Santich et al that binds to CD45 or CD34 and myosin light chain would have the advantage of targeting a exogenous stem cells to repair cardiac tissue. Furthermore, substituting the tetravalent bispecific antibody (T-BiAb) of Santich et al for the bispecific antibody of Lee et al would be seen as
as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results because one of skill in the art reading Lee et al would have recognized that the recombinant tetravalent, bispecific antibody structure of Santich et al could be used as a stem cell targeting antibody when the antibody was engineered to bind CD45 or CD34 and myosin light chain.
While it is noted that the prior art does not specifically disclose that the antibody or the antibody-targeted stem cells contact β-cells in diabetic patients, as evidenced above intravenous administration of the antibody or the antibody-targeted stem cells would enter systemic circulation and accordingly, necessarily contact β-cells. Therefore, while the original intent of the prior art is to repair injured cardiac tissue, the methods suggested by the prior art would also contact β-cells in diabetic patients with DCM such that the methods suggested by the prior art are broadly, but reasonably encompassed by the instant claims (see MPEP § 2112).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a showing otherwise.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
September 4, 2026
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