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 .
Claims 1-22 are pending and currently under consideration.
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 3 and 19 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 3 is rejected for awkwardly reciting a construct comprising a signal peptide “before” the peptidic moiety (a). The metes-and-bounds of the claim are unclear because it is not clear what signal peptide would, or would not, be considered “before” the peptidic moiety (a).
Claim 19 is rejected because it is unclear how, or if, limitations following the term “preferably” limit the claim.
Claim Rejections - 35 USC § 112
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 6-7 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(s) contains subject matter which 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(s), at the time the application was filed, had possession of the claimed invention. In the instant case, the claims are inclusive of a genus of ACE2 and binding domains thereof and peptides comprising SEQ ID NO:2 (ACE2 polypeptide) or variants at least 85% identical thereto that have the function of binding ACE2 (see limitation “(ii)” of claim 1). The specification does not disclose, and the art does not teach, the genus as broadly encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.” The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here.
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of members that encompass the genus nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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.
Claims 1-5, 8, 11-16, and 19-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Rezvani et al (WO 2021/232050 A1; 11/18/2021) in view of Friesen et al (WO 2021/201679 A1; 10/7/2021).
Rezvani et al teaches recombinant NK cells that target SARS-COV-2 that are to be administered to treat SARS-COV-2 viral infection (Abstract, in particular). SARS-COV-2 is the virus that causes Covid-19 ([0044], in particular). Rezvani et al further teaches the NK cells as comprising engineered chimeric antigen receptors (CARs) and/or engineered T cell receptors (TCRs) to target SARS-COV-2 antigens ([0007], in particular). Rezvani et al further teaches the NK cells where the engineered CARs and TCRs targets the spike protein of the SARS-COV-2 virus ([0010] and [0048), in particular). Rezvani et al further teaches the NK cells where the engineered receptor is a CAR with an scFv extracellular domain specific for the spike protein of SARS-COV-2 ([0058], in particular). Rezvani et al further teaches the CAR wherein the scFv is specific for the spike protein of SARS-CoV (same as SARS-COV-1), as opposed to SARS-COV-2 ([0050], in particular). Rezvani et al further teaches the CAR can comprise the extracellular antigen-binding (spike binding) domain is fused to a transmembrane domain comprising a transmembrane region of TCRa, TCRb, CD3e, CD3g, or CD3d protein and intracellular signaling domains ([0070]-[0071], in particular). Rezvani et al further teaches the CAR wherein a triplet of phenylalanine, tryptophan and valine links the extracellular antigen binding domain to the transmembrane domain ([0071], in particular). Rezvani et al further teaches a transfecting a DNA vector encoding the CAR of Rezvani et al into cells ([0068], in particular). Rezvani et al further teaches a method of treating a subject with a SARS-COV-2 infection comprising administering the recombinant NK cells to the subject ([0015], in particular). Rezvani et al further teaches the treatment is to ameliorate a sign or symptom related to a disease or pathological condition such as a sign or symptom related to viral infection ([0035], in particular). The CAR of the recombinant NK cells of Rezvani et al are “T cell receptor fusion constructs”, as defined by the instant specification (third paragraph on page 14 of the instant specification, in particular).
Rezvani et al does not specifically teach SARS-COV-2 spike protein binds ACE2, does not teach a signal peptide “before” the scFv extracellular domain of the CAR, and does not teach the CAR wherein the scFv extracellular domain specific for the spike protein is specific for an HCoV-NL63 coronavirus. However, these deficiencies are made up in the teachings of Friesen et al.
Friesen et al teaches SARS-COV-2 spike protein binds ACE2 (paragraph spanning pages 31-32, in particular). Friesen et al adding a signal peptide to the extracellular domains of CARs to direct the CARs to the endoplasmic reticulum (ER) for processing (lines 9-14 on page 18, in particular). One of skill in the art would recognize directing CARs to the ER for processing is crucial for proper folding, assembly, and eventual surface expression of the CARs. At lines 17-26 on page 1, Friesen et al further teaches NL63 (same as “HCoV-NL63”) as a human coronavirus (like SARS-COV-2 and SARS-COV of Rezvani et al) that has a spike protein that is responsible for interaction of most coronaviruses and host cells (lines 1-2 on page 2, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising generating and administering the recombinant NK cells of Rezvani et al wherein SARS-COV-2 spike protein binds ACE2 and the CAR of the recombinant NK cells comprises a signal peptide at the end of the scFv extracellular domain of the CAR because Friesen et al teaches SARS-COV-2 spike protein binds ACE2 (paragraph spanning pages 31-32, in particular), Friesen et al teaches adding a signal peptide to the extracellular domains of CARs to direct the CARs to the endoplasmic reticulum (ER) for processing (lines 9-14 on page 18, in particular), and one of skill in the art would recognize directing CARs to the ER for processing is crucial for proper folding, assembly, and eventual surface expression of the CARs.
In particular regards to claims 14 and 22, one of ordinary skill in the art would have been further motivated, with a reasonable expectation of success, to perform said combined method wherein the scFv extracellular domain specific for the spike protein is specific for an HCoV-NL63 coronavirus in order to treat patients with HCoV-NL63 because Friesen et al teaches NL63 (same as “HCoV-NL63”) as a human coronavirus (like SARS-COV-2 and SARS-COV of Rezvani et al) that has a spike protein that is responsible for interaction of most coronaviruses and host cells (lines 1-2 on page 2, in particular). This is an example of a simple substitution of one known element for another to obtain predictable results.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 1-5, 8, and 11-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Rezvani et al (WO 2021/232048 A1; 11/18/2021; “Rezvani1”) in view of Rezvani et al (WO 2021/232050 A1; 11/18/2021; “Rezvani2”) in view of Friesen et al (WO 2021/201679 A1; 10/7/2021).
Rezvani1 teaches methods of generating recombinant SARS-CoV-2 specific T cells that are to be administered to treat SARS-COV-2 viral infection ([0008], in particular). Rezvani1 further teaches said SARS-CoV-2 specific T cells further comprising chimeric antigen receptors (CARs) or T-cell receptors (TCRs) that target one or more SARS-CoV-2 viral antigens ([0092], in particular). Rezvani1 further teaches expanding T cells ex vivo ([0069] and [0079], in particular).
Rezvani1 does not specifically teach CARs or TCRs that target “spike” as the SARS-COV-2 viral antigen. However, these deficiencies are made up in the teachings of Rezvani2 in view of Friesen et al.
Rezvani2 teaches cells comprising engineered chimeric antigen receptors (CARs) and/or engineered T cell receptors (TCRs) to target SARS-COV-2 antigens ([0007], in particular). Rezvani2 further teaches the cells where the engineered CARs and TCRs targets the spike protein of the SARS-COV-2 virus ([0010] and [0048), in particular). Rezvani2 further teaches the cells where the engineered receptor is a CAR with an scFv extracellular domain specific for the spike protein of SARS-COV-2 ([0058], in particular). Rezvani2 further teaches the CAR wherein the scFv is specific for the spike protein of SARS-CoV (same as SARS-COV-1), as opposed to SARS-COV-2 ([0050], in particular). Rezvani2 further teaches the CAR can comprise the extracellular antigen-binding (spike binding) domain is fused to a transmembrane domain comprising a transmembrane region of TCRa, TCRb, CD3e, CD3g, or CD3d protein and intracellular signaling domains ([0070]-[0071], in particular). Rezvani2 further teaches the CAR wherein a triplet of phenylalanine, tryptophan and valine links the extracellular antigen binding domain to the transmembrane domain ([0071], in particular). Rezvani2 further teaches a transfecting a DNA vector encoding the CAR of Rezvani2 into cells ([0068], in particular). Rezvani2 further teaches a method of treating a subject with a SARS-COV-2 infection comprising administering the recombinant NK cells to the subject ([0015], in particular). Rezvani2 further teaches the treatment is to ameliorate a sign or symptom related to a disease or pathological condition such as a sign or symptom related to viral infection ([0035], in particular).
Friesen et al teaches SARS-COV-2 spike protein binds ACE2 (paragraph spanning pages 31-32, in particular). Friesen et al adding a signal peptide to the extracellular domains of CARs to direct the CARs to the endoplasmic reticulum (ER) for processing (lines 9-14 on page 18, in particular). One of skill in the art would recognize directing CARs to the ER for processing is crucial for proper folding, assembly, and eventual surface expression of the CARs. At lines 17-26 on page 1, Friesen et al further teaches NL63 (same as “HCoV-NL63”) and SARS-COV-1 as human coronaviruses (like SARS-COV-2 of Rezvani2) that have a spike protein that is responsible for interaction of most coronaviruses and host cells (lines 1-2 on page 2, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising generating and administering the recombinant T cells of Rezvani1 wherein the CAR receptor is a CAR receptor of Rezvani2 that binds spike protein as the SARS-COV-2 viral antigen because Rezvani1 teaches the CARs are to target one or more SARS-CoV-2 viral antigens and the CAR of Rezvani2 that binds spike protein is a CAR that targets one or more SARS-CoV-2 viral antigens. This is an example of a simple substitution of one known element for another to obtain predictable results.
SARS-COV-2 spike protein of Rezvani2 binds ACE2 (paragraph spanning pages 31-32 of Friesen et al, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein CAR generated in the recombinant T cells of the combined method by transfecting the T cells with a DNA vector encoding the CAR of the combined method with an N-terminal signal peptide at the end of the scFv extracellular domain of the CAR and expanding the cells ex vivo because Rezvani2 expressing CARs in cells by transfecting a DNA vector encoding the CAR of Rezvani2 into cells ([0068], in particular), expanding the CAR-expressing T cells ex vivo (as taught by Rezvani1 and Rezvani2) would provide more T cells to administer, Friesen et al teaches adding a signal peptide to the extracellular domains of CARs to direct the CARs to the endoplasmic reticulum (ER) for processing (lines 9-14 on page 18, in particular), and one of skill in the art would recognize directing CARs to the ER for processing is crucial for proper folding, assembly, and eventual surface expression of the CARs.
Further, one of ordinary skill in the art would have been further motivated, with a reasonable expectation of success, to perform said combined method wherein the scFv extracellular domain specific for the spike protein is specific for an HCoV-NL63 coronavirus or SARS-COV-1 in order to treat patients with HCoV-NL63 or SARS-COV-1 because Friesen et al teaches SARS-COV-1 and NL63 (same as “HCoV-NL63”) as human coronaviruses (like SARS-COV-2 of Rezvani2) that have a spike protein that is responsible for interaction of most coronaviruses and host cells (lines 1-2 on page 2, in particular). This is an example of a simple substitution of one known element for another to obtain predictable results.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-5, 8-16, and 19-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rezvani et al (WO 2021/232050 A1; 11/18/2021) in view of Friesen et al (WO 2021/201679 A1; 10/7/2021) as applied to claims 1-5, 8, 11-16, and 19-22 above, and further in view of Prachasuphap et al (Bulletin of the Department of Medical Sciences, 2020, 6(3): 155-166), as evidenced by WO2021/170090 A1 (2/26/2021).
Teachings of Rezvani et al and Friesen et al are discussed above.
Rezvani et al and Friesen et al do not specifically teach the scFv extracellular domain specific for the spike protein of SARS-COV-2 comprises a variable heavy chain (VH) set-forth as instant SEQ ID NO:6 connected by a peptide liker to a variable light chain (VL) set-forth as instant SEQ ID NO:5. However, these deficiencies are made up in the teachings of Prachasuphap et al.
Prachasuphap et al teaches a recombinant scFv generated from “CR3022 antibody”, comprising the VH of the CR3022 antibody connected by a peptide linker to the VL of the CR3022 antibody (page 157; in particular), that has been proven to bind “potently” with recombinant spike protein of SARS-COV-2 (page 163, in particular). As evidenced by WO2021/170090 A1, CR3022 antibody of Prachasuphap et al has a VH consisting of SEQ ID NO:6 (identical to instant SEQ ID NO:6) and a VL consisting of SEQ ID NO:7 (identical to instant SEQ ID NO:5) (see Abstract, second full paragraph below descriptions of drawings, and sequences on page 22, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Rezvani et al and Friesen et al comprising generating and administering the recombinant NK cells wherein the scFv extracellular domain of the CAR that binds the spike protein of SARS-COV-2 is the scFv of Prachasuphap et al because the scFv of Prachasuphap et al has been proven to bind “potently” with recombinant spike protein of SARS-COV-2 (page 163, in particular). This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-5 and 8-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rezvani et al (WO 2021/232048 A1; 11/18/2021; “Rezvani1”) in view of Rezvani et al (WO 2021/232050 A1; 11/18/2021; “Rezvani2”) in view of Friesen et al (WO 2021/201679 A1; 10/7/2021) as applied to claims 1-5, 8, and 11-22 above, and further in view of Prachasuphap et al (Bulletin of the Department of Medical Sciences, 2020, 6(3): 155-166), as evidenced by WO2021/170090 A1 (2/26/2021).
Teachings of Rezvani1, Rezvani2, and Friesen et al are discussed above.
Rezvani1, Rezvani2, and Friesen et al do not specifically teach the scFv extracellular domain specific for the spike protein of SARS-COV-2 comprises a variable heavy chain (VH) set-forth as instant SEQ ID NO:6 connected by a peptide liker to a variable light chain (VL) set-forth as instant SEQ ID NO:5. However, these deficiencies are made up in the teachings of Prachasuphap et al.
Prachasuphap et al teaches a recombinant scFv generated from “CR3022 antibody”, comprising the VH of the CR3022 antibody connected by a peptide linker to the VL of the CR3022 antibody (page 157; in particular), that has been proven to bind “potently” with recombinant spike protein of SARS-COV-2 (page 163, in particular). As evidenced by WO2021/170090 A1, CR3022 antibody of Prachasuphap et al has a VH consisting of SEQ ID NO:6 (identical to instant SEQ ID NO:6) and a VL consisting of SEQ ID NO:7 (identical to instant SEQ ID NO:5) (see Abstract, second full paragraph below descriptions of drawings, and sequences on page 22, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Rezvani1, Rezvani2, and Friesen et al comprising generating and administering the recombinant T cells wherein the scFv extracellular domain of the CAR that binds the spike protein of SARS-COV-2 is the scFv of Prachasuphap et al because the scFv of Prachasuphap et al has been proven to bind “potently” with recombinant spike protein of SARS-COV-2 (page 163, in particular). This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642