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 .
Claim status
In this compact prosecution, examiner is pursuing the amended claims dated 28 July 2022, in which applicant canceled claims 1-56 and added new claims 57-76. Therefore, claims 57-76 are herein pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 57, 61, and 63 drawn to a universal immune receptor fusion protein comprising, a SpyCatcher extracellular binding domain in the reply filed on 19 September 2025 is acknowledged.
There was a typographic error in the restriction filed on 06/20/2025, claim 67 should be listed in the group II. Therefore, claims 58-60, 62, and 64-76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 57, 61, and 63 are under current examination.
Priority
Applicant’s claim for the benefit of a prior-filed application, provisional application 16064875 is a National Stage entry of PCT/US2016/068055 filed on December 21, 2016, which claims benefit to the priority from provisional application 62271071, filed on December 22, 2015.
Accordingly, the effective priority date of the instant application is granted as December 22, 2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 19 May 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Claim Rejections - 35 USC § 112(a)
(Written description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 57 and 63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor, at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Claim 57 is broadly drawn to the genus of any universal immune receptor fusion protein, comprising, in order, the genus of any SpyCatcher extracellular binding domain, the genus of any extracellular hinge region, the genus of any transmembrane domain, the genus of any costimulatory molecule and the T cell receptor comprises the genus of any intracellular signaling domain. Claim 63 broadly drawn to the genus of any universal immune receptor fusion protein, comprising, in order, the genus of any SpyCatcher extracellular binding domain, the genus of any extracellular hinge region, the genus of any transmembrane domain, and the T cell receptor comprises the genus of any intracellular signaling domain. However, the disclosure as originally filed does not provide adequate written description support for the full breadth of the invention as presently claimed.
The specification discloses that the universal immune receptor of the invention comprises a SpyCatcher domain, a human CD8 alpha hinge and transmembrane domain, and a CD28 and CD3-zeta intracellular signaling domains ([0137] of US20220281944A1). Furthermore, the universal immune receptor comprising either a SpyCatcher extracellular binding domain bound to an extracellular hinge region and the universal immune receptor comprises a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 1, 3, 5, 7, 9, 11, 13 and 15, or selected from the group consisting of SEQ ID Nos: 5, 7, 13 and 15, or selected from the group consisting of SEQ ID Nos: 1, 3, 9 and 11 ([0007], [0009] of US20220281944A1). The T cell receptor intracellular signaling domain further comprises a costimulatory molecule and the intracellular domain of the costimulatory molecule is selected from the group consisting of CD27, CD28, CD2, CD3, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof ([0007], [0009] of US20220281944A1). Therefore, SPEC has specific adequate support for specific molecules associated with a specific type of immune receptor fusion protein.
Therefore, the specification fails to adequately describe the full scope of claims 57 and 63. The specification supports only a narrow scope of the inventive concept as described in above, but does not provide support for the full scope of the product of any universal immune receptor fusion protein, comprising, in order, any SpyCatcher extracellular binding domain, any extracellular hinge region, any transmembrane domain, any costimulatory molecule and the T cell receptor comprises any intracellular signaling domain.
In the prior art Reddington et al., (Current opinion in chemical biology, 29, pp.94-99, 2013; cited in PTO892; hereinafter “Reddington”) discloses that the SpyTag is a short peptide that forms an isopeptide bond upon encountering its protein partner SpyCatcher. This covalent peptide interaction is a simple and powerful tool for bioconjugation and extending what protein architectures are accessible (abstract of Reddington). Reddington illustrates the splitting CnaB2 into SpyCatcher (grey) and SpyTag (red) and the residues forming the isopeptide are shown as sticks (based on PDB 2X5P and 4MLI). The environment of the isopeptide bond between Asp117 (carbons orange) and Lys31 (carbons yellow), facilitated by Glu77 (carbons grey) (see Fig.1 of Reddington). Furthermore, Zhang et al. (J. Am. Chem. Soc. 2013, 135, 37, 13988–13997; cited in PTO892; hereinafter “Zhang”) provides the controlling macromolecular topology with genetically encoded SpyTag−SpyCatcher chemistry and demonstrates the topological effects on the material properties and self-assembly behavior of several genetically encoded SpyTag−SpyCatcher as listed in the Fig. 1 of Zhang). Therefore, the SpyTag and SpyCatcher technology, also termed “molecular superglue”, has been employed by the scientific community in many ways to build proteins with novel properties, and several genetically encoded SpyCatcher is well known Products and commercially available in the marker as listed by Bio-RAD (see the attachment; cited in PTO892). Accordingly, it is obvious that any SpyCatcher is not established at the time of filling and POSITA cannot predictably identify any SpyCatcher encoded to the extracellular binding domain that exercise in instant invention of making any universal immune receptor fusion protein.
Furthermore, Davila et al. (US20130287752A1; cited in IDS filed: 05/19/2022; hereinafter “Davila”) engineering a universal immune receptor on T cells that comprises a targeting motif that recognizes corresponding antibodies attached on tumor cells containing a targeted motif (i.e., a motif that the targeting motif on the universal immune receptor is directed towards) (abstract, [0096]). Davila also teaches that the receptor comprises a targeting binding domain that binds to a targeted molecule (and is therefore on the extracellular side of the cell's membrane), which is ideally an antibody, and that this targeting binding domain is attached to a transmembrane domain which is in turn attached to an intracellular activation domain [0013]. Davila further also teaches that the intracellular activation domain can comprise the cytoplasmic region of CD28 ([0013], Fig. 1A), which is a T-cell intracellular signaling domain given the presence of the cytoplasmic region of CD137 (41BB), OX40, HVEM, CD3s and FcRE ([0013], [0042], claim 13). Therefore, this disclosure necessarily renders obvious claim 61. Davila also teaches that the transmembrane region can be optionally linked to a hinge [0041], and that this hinge can be linked to an scFv targeting binding domain that binds to FITC-targeted antibodies [0072], meaning that the hinge would have to be located on the extracellular side of the membrane. Therefore, it is obvious that prior art does not support to identify the genus of any extracellular hinge region, the genus of any transmembrane domain, the genus of any costimulatory molecule and the T cell receptor with the genus of any intracellular signaling domain to prepare the universal immune receptor of Davila.
The prior art does not support to identify any universal immune receptor fusion protein, comprising, in order, any SpyCatcher extracellular binding domain, any extracellular hinge region, any transmembrane domain, any costimulatory molecule and the T cell receptor comprises any intracellular signaling domain. Accordingly at the time of filling any universal immune receptor fusion protein is not well established and POSITA cannot predictably identify any extracellular hinge region, any transmembrane domain, any costimulatory molecule and the T cell receptor of any intracellular signaling domain that exercise in this invention to prepare any universal immune receptor fusion protein.
Therefore, it concludes that the claimed genus of any universal immune receptor fusion protein, comprising, in order, any SpyCatcher extracellular binding domain, any extracellular hinge region, any transmembrane domain, any costimulatory molecule and the T cell receptor comprises any intracellular signaling domain doesn't have an adequate written description. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed in claims 57, and 63.
Claim Rejections - 35 USC § 102(a)(2)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102(a)(2) 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)(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.
Claim 57, 61 and 63 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Young et al., (US10800828B2; Provisional application No. 62138901, filed on Mar. 26, 2015; cited in PTO892; hereinafter “Young”.).
[AltContent: textbox ([img-media_image1.png]
Fig.1.)]Examiner’s claims 57 and 63 interpretation: The termed universal immune receptors (UIRs) maintain a relatively similar structure to CARs but contain an extracellular adapter domain that functions as an orthogonal bridge between intracellular T cell signaling domains and a soluble tumor antigen targeting ligand. Unlike the CAR approach, UIR is coupling antigen recognition and T-cell signaling domains via SpyCatcher-SpyTag chemistry (see abstract of Minutolo et al. (J. Am. Chem. Soc. 2020, 142, 14, 6554–6568; cited in PTO892). Therefore, the SpyCatcher-SpyTag chemistry is one of the mechanisms to implement UIR onto T cell, where an isolated universal immune receptor comprising either a SpyCatcher or a SpyTag extracellular binding domain bound to an extracellular hinge region, which is in turn bound to a transmembrane domain which is in turn bound to a T cell receptor intracellular signaling domain. According to instant SPEC (see [0009] ¶ of US20220281944A1) the SpyCatcher extracellular binding domain is bound to the extracellular hinge domain as illustrated in Fig.1.
With respect to claims 57, 61 and 63, Young teaches a chimeric receptor (i.e., antigen-specific targeting ligands; e.g., anti-CD19, anti-CD22 or anti-BCMA antibody) in order comprising a non-antibody extracellular domain that interacts with a chimeric receptor binding partner, wherein the chimeric receptor binding partner is located on a switch that interacts with a target cell; a transmembrane domain; and an intracellular signaling domain, wherein the intracellular signaling domain signals to an effector cell on which the chimeric receptor is expressed when the non-antibody extracellular domain interacts with the chimeric receptor binding partner (Col. 2 lns. 1-12). Young also discloses that the chimeric receptor binding partner comprises spytag and the non-antibody extracellular domain comprises spycatcher (Col. 3 lns 17-19; Col. 6 lns 37-39; Fig. 3). An extracellular hinge region (i.e., CD8) a transmembrane domain (i.e., CD8), a costimulatory molecules (i.e., 4-1BB, limitation of claim 61) and intracellular signaling domain CD3 zeta (Col 79 lns 58-64). Furthermore, Young discloses that intercellular domain may comprise OX-40 or ICOS (limitation of claim 63; Col. 17 lns 23-30), therefore, it anticipates costimulatory molecules OX40 or ICOS.
Accordingly, Young anticipates the universal immune receptor fusion protein and claims 57, 61 and 63.
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 of this title, 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.
Claims 57, 61 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Davila et al. (US20130287752A1; cited in IDS filed: 05/19/2022; hereinafter “Davila”), in view of Kahvejian et al. (US20150306212A1; published on: Oct. 29, 2015; cited in IDS filed: 05/19/2022; hereinafter “Kahvejian”).
[AltContent: textbox ([img-media_image2.png])]Regarding claims 57, 61 and 63, Davila teaches engineering a universal immune receptor on T cells that comprises a targeting motif that recognizes corresponding antibodies attached on tumor cells containing a targeted motif (i.e., a motif that the targeting motif on the universal immune receptor is directed towards) (abstract, [0096]). Davila also teaches that the receptor comprises a targeting binding domain that binds to a targeted molecule (and is therefore on the extracellular side of the cell's membrane), which is ideally an antibody, and that this targeting binding domain is attached to a transmembrane domain which is in turn attached to an intracellular activation domain [0013]. Davila further also teaches that the intracellular activation domain can comprise the cytoplasmic region of CD28 ([0013], Fig. 1A), which is a T-cell intracellular signaling domain given the presence of the cytoplasmic region of CD137 (41BB), OX40, HVEM, CD3s and FcRE ([0013], [0042], claim 13). Therefore, this disclosure necessarily renders obvious claim 61. Davila also teaches that the transmembrane region can be optionally linked to a hinge [0041], and that this hinge can be linked to an scFv targeting binding domain that binds to FITC-targeted antibodies [0072], meaning that the hinge would have to be located on the extracellular side of the membrane (see the Fig. illustration).
Although Davila discloses the tag-binding domain (i.e., antibody or an antigen-binding fragment (scFv) thereof) specifically binds FITC, biotin, PE, histidine or streptavidin which bioconjugate with the transmembrane domain and the activation domain. Still, Davila does not teach that the extracellular binding domain comprises a Spycatcher, However, such was known in the prior art.
Kahvejian teaches that a Spycatcher isopeptidase can be located on the surface of a cell (i.e., T cell [0010], [0013], [0627]) and fused to the extracellular region of a transmembrane protein [0279], and also that the Spycatcher can further be fused to a receiver polypeptide (para [0279], [0424]), which can optionally be an antibody or scFv [0559]. Kahvejian also teaches that the Spycatcher can covalently bind to a Spytag motif [0279] to develop an adoptive T cell therapy, wherein the T cells are targeted to tumor targets so as to reduce off-target toxicity [0013], and that embodiments of its invention can be directed to T cell therapy [0013]-[0014].
MPEP 2143 (B) states that simple substitution of one known element for another to obtain predictable results. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Accordingly, it would have been obvious to practice the universal immune receptor of Davila and substitute Spycatcher in the extracellular binding domain as taught by Kahvejian with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Kahvejian because the Spycatcher motif fused to the extracellular side of a transmembrane protein can be used to target and bind to a separate cell comprising a Spytag motif, similar to the mechanism of action of the targeting binding domain of Davila, and Kahvejian, like Davila, also directs its compositions to adoptive T cell therapy ([0013]-[0014] of Kahvejian). The POSITA would have a reasonable expectation of success of substituting the targeting binding domain of a universal immune receptor taught by Davila to instead comprise a Spycatcher motif as taught by Kahvejian because Kahvejian teaches that its invention can also be used to target T cells to pathogenic cells ([0884] of Kahvejian). In regard to the reasonable expectation of success in doing so substitute Spycatcher in the extracellular binding domain of Kahvejian had a reasonable expectation of success since the steps thereof required no more than recombinant DNA and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633