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
Amendment filed May 27, 2025.
Claims 92-107 are pending. Claims 1-91 are canceled. Claims 106-107 are withdrawn. Claims 92-105 are examined.
Claim Rejections - 35 USC § 112
Claims 92-105 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.
Claims encompass the terms which encompasses unlimited changes to the structure. Terms such as chimeric antigen receptor, ligand binding domain of nuclear receptor, co-regulator of nuclear receptor, dimerization agent, LBD of estrogen receptor, N-Cor, 4-IBB, co-stimulatory domains encompass generically unlimited changes to the structure of the molecule. The genus of polynucleotide encoding the polypeptides as claimed includes variations in the entire polypeptide. The genus of polynucleotide encoding the polypeptides as claimed includes all species of vertebrate and/or invertebrate animal’s polynucleotide encoding the entire polypeptide. The specification discloses the immune cell comprising specific polynucleotide encoding polypeptides with specific amino acid sequence . However, the specification does not disclose the immune cell comprising unlimited genus of structures for the polynucleotide encoding polypeptide. Thus, applicant was not in possession of the immune cell comprising a broad genus of polynucleotide encoding the polypeptide as claimed.
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d. Additionally, “a patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.” Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed. Cir. 2004).
A “representative number of species” means that the species which are adequately described are representative of the entire 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
The specification discloses immune cells comprising specific polynucleotide encoding polypeptides of specified amino acid sequence as examples. However, the specification does not provide sufficient written description as to the structural features of the claimed genus of polynucleotide encoding polypeptides and the correlation between the structure and function of the genus of variants, such as structural region that are essential for function.
It has been well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. Based on the instant disclosure one of skill in the art would not know which structural regions are essential, which residues are non-essential and what particular sequence lengths identify essential sequences for identifying a chimeric polypeptide encompassed by the claimed specificity. Mere idea of function is insufficient for written description; isolation and characterization at a minimum are required.
Dasgupta et al. (2014) teach that the skilled artisan is well aware that specific polypeptide with specific amino acid sequence can be constructed. However, the claims do not provide structure or structural regions for the functional limitations. The state of the art is silent regards to envisioning estrogen receptor and N-CoR species whose protein structures which are not known. Even in situations where there is some confidence of a similar overall structure between binding domain only experimental research can confirm the artisan’s best guess as to function of the structurally related inhibitors.
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
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, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, 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 isolating it. 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.
One cannot describe what one has not conceived. See Fiddles v.Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Therefore, only immune cell comprising the polynucleotide encoding polypeptide comprising specified amino acid sequence, but not the full breadth of the claim meets the written description provision of 35 U.S.C. § 112, first paragraph. 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).
Applicants argue that the specification provides ample description of antigen binding domains, intracellular signaling domains and co-stimulatory domains and such domains are well-known in the art and thus the specification provides sufficient written description. However, the specification discusses in generic terms without discussion of variants and mutants which are encompassed by the terms. The specification does not disclose the structure- function relationship of the large genus of variants effect on function of the CAR in combination with other large genus of variants domains.
Applicants argue that the specirication provides amino acid sequences of the encompassed co-regulators and identifies the corresponding nuclear hormone receptors of the LBD. However, the specification discusses in generic terms without discussion of variants and mutants which are encompassed by the terms. The specification does not disclose the structure- function relationship of the large genus of variants effect on function of the CAR in combination with other large genus of variants domains.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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Claims 92-105 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,136,562 in view of Duchateau et al. (US 2017/0292118), Gurevich et al. (Toxicol. Appled Pharmacol., 2007), Ostermeir et al. (US 8,492,122), Klein et al. (US 2003/0003517).
Claims 1-18 of U.S. Patent No. 11,136,562 disclose the nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR. ‘562 does not teach the LBD domain of nuclear receptor on one heterodimer CAR and co-regulator of a nuclear receptor on the second heterodimer CAR. ‘562 does not teach the co-regular of the nuclear hormone receptor has a length of up to 50 amino acids. Claims do not teach the immune cell.
Duchateau et al. disclose the immune cell comprising nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR (paragraph 1, 8, 32, 33, 159-160). Duchateau does not teach the the LBD domain of nuclear receptor on one CAR and co-regulator of a nuclear receptor on the second CAR. Duchateau does not teach the 4-1BB in the CAR.
Gurevich et al. teach the corepressor and coregulatory ligand dependent interaction with nuclear receptor (Abstract; Figure 1; pages 289-291, 292-294). Gurevich et al. teach corepressors which bind nuclear receptor with ligand such as LCoR and estrogen receptor (page 289-290).
Ostermeier et al. disclose nucleic acid encoding molecules which dimerize by molecular switches which are induced by agents including estrogen receptor (abstract, columns 1-2).
Klein et al. disclose nucleic acid encoding estrogen receptor and N-CoR which dimerize (paragraphs 4, 9, 10, 21).
It would be obvious to one of ordinary skill in the art at the filing date of the invention to incorporate the molecular switch dimerization of LCoR and estrogen receptor as taught by Duchateau, Gurecivh, Ostermeier and Klein into the CAR dimerization pair as taught by ‘562. The ‘562 claims placing the importance of dimerization in the CAR provides motivation to modify dimerization domains for optimization of CAR using the dimerization properties as taught by Gurevich, Ostermeier and Klein. One of ordinary skilled in the art would be motivated by analogous ease of using nuclear receptor dimers in the similar manner as ‘012 dimer switches which are very similar. One of ordinary skill in the art would be motivated by Ostermeier presentation of molecular switch using nuclear receptors such as estrogen receptor. One of ordinary skill in the art are aware as taught by Klein that estrogen receptor and LCoR dimerize and are controlled by ligand. The estrogen receptor and LCoR inherently have the same sequences as claimed. Gurevich et al. provides further support for the interaction of nuclear receptors with co-regulators. It would be obvious to use the agonists of estrogen receptor for the ‘562 claim small molecule dimerizer.
It would be obvious to one of ordinary skill in the art at the time of the filing date of the invention to modify the CAR as taught by ‘562 claims, Duchateau, Gurevich, Ostermeier, and Klein as discussed above by having a co-regulator with the length of up to 50 amino acids. One of ordinary skill in the art would be motivated to modify the size of the co-regulator to optimize the function of the CAR. One of ordinary skill in the art would also be motivated by the teaching of Ostermeier that size of insertion for the fusion molecules will vary depending on the desired particular state (column 12, lines 22-63). Gurevich teach the important box regions for the dimerization of the nuclear receptor to the co-regulator which are leucine rich regions (page 2 and 10).
Applicants request that the rejections be held in abeyance untila patentable subject matter has been identified. The rejection is maintained.
Claims 92-105 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 9.821,012 in view of Duchateau et al. (US 2017/0292118), Gurevich et al. (Toxicol. Appled Pharmacol., 2007), Ostermeir et al. (US 8,492,122), Klein et al. (US 2003/0003517).
Claims 1-27 of U.S. Patent No. 9.821,012 disclose the nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR. ‘012 does not teach the LBD domain of nuclear receptor on one heterodimer CAR and co-regulator of a nuclear receptor on the second heterodimer CAR. ‘012 does not teach the co-regular of the nuclear hormone receptor has a length of up to 50 amino acids. Claims do not teach the immune cell.
Duchateau et al. disclose the immune cell comprising nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR (paragraph 1, 8, 32, 33, 159-160). Duchateau does not teach the the LBD domain of nuclear receptor on one CAR and co-regulator of a nuclear receptor on the second CAR. Duchateau does not teach the 4-1BB in the CAR.
Gurevich et al. teach the corepressor and coregulatory ligand dependent interaction with nuclear receptor (Abstract; Figure 1; pages 289-291, 292-294). Gurevich et al. teach corepressors which bind nuclear receptor with ligand such as LCoR and estrogen receptor (page 289-290).
Ostermeier et al. disclose nucleic acid encoding molecules which dimerize by molecular switches which are induced by agents including estrogen receptor (abstract, columns 1-2).
Klein et al. disclose nucleic acid encoding estrogen receptor and N-CoR which dimerize (paragraphs 4, 9, 10, 21).
It would be obvious to one of ordinary skill in the art at the filing date of the invention to incorporate the molecular switch dimerization of LCoR and estrogen receptor as taught by Duchateau, Gurecivh, Ostermeier and Klein into the CAR dimerization pair as taught by ‘012. The ‘012 claims placing the importance of dimerization in the CAR provides motivation to modify dimerization domains for optimization of CAR using the dimerization properties as taught by Gurevich, Ostermeier and Klein. One of ordinary skilled in the art would be motivated by analogous ease of using nuclear receptor dimers in the similar manner as ‘012 dimer switches which are very similar. One of ordinary skill in the art would be motivated by Ostermeier presentation of molecular switch using nuclear receptors such as estrogen receptor. One of ordinary skill in the art are aware as taught by Klein that estrogen receptor and LCoR dimerize and are controlled by ligand. The estrogen receptor and LCoR inherently have the same sequences as claimed. Gurevich et al. provides further support for the interaction of nuclear receptors with co-regulators. It would be obvious to use the agonists of estrogen receptor for the ‘012 claim small molecule dimerizer.
It would be obvious to one of ordinary skill in the art at the time of the filing date of the invention to modify the CAR as taught by ‘012 claims, Duchateau, Gurevich, Ostermeier, and Klein as discussed above by having a co-regulator with the length of up to 50 amino acids. One of ordinary skill in the art would be motivated to modify the size of the co-regulator to optimize the function of the CAR. One of ordinary skill in the art would also be motivated by the teaching of Ostermeier that size of insertion for the fusion molecules will vary depending on the desired particular state (column 12, lines 22-63). Gurevich teach the important box regions for the dimerization of the nuclear receptor to the co-regulator which are leucine rich regions (page 2 and 10).
Applicants request that the rejections be held in abeyance untila patentable subject matter has been identified. The rejection is maintained.
Claims 92-105 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,105,391 in view of Duchateau et al. (US 2017/0292118), Gurevich et al. (Toxicol. Appled Pharmacol., 2007), Ostermeier et al. (US 8,492,122), Klein et al. (US 2003/0003517),
Claims 1-27 of U.S. Patent No. 10,105,391 disclose the nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR (paragraph 1, 8, 32, 33, 159-160). ‘391 does not teach the LBD domain of nuclear receptor on one heterodimer CAR and co-regulator of a nuclear receptor on the second heterodimer CAR. ‘391 does not teach the co-regulator of the nuclear hormone receptor has a length of up to 50 amino acids. Claims do not teach the immune cell.
Duchateau et al. disclose the nucleic acid encoding chimeric antigen receptor (CAR) comprising chemically induced dimerization domain where the chemical agent induces the dimerization of the CAR (paragraph 1, 8, 32, 33, 159-160). Duchateau does not teach the the LBD domain of nuclear receptor on one CAR and co-regulator of a nuclear receptor on the second CAR. Duchateau does not teach the 4-1BB in the CAR.
Gurevich et al. teach the corepressor and coregulatory ligand dependent interaction with nuclear receptor (Abstract; Figure 1; pages 289-291, 292-294). Gurevich et al. teach corepressors which bind nuclear receptor with ligand such as LCoR and estrogen receptor (page 289-290).
Ostermeier et al. disclose nucleic acid encoding molecules which dimerize by molecular switches which are induced by agents including estrogen receptor (abstract, columns 1-2).
Klein et al. disclose nucleic acid encoding estrogen receptor and N-CoR which dimerize (paragraphs 4, 9, 10, 21).
It would be obvious to one of ordinary skill in the art at the filing date of the invention to incorporate the molecular switch dimerization of LCoR and estrogen receptor as taught by Duchateau, Gurecivh, Ostermeier and Klein into the CAR dimerization pair as taught by ‘391. The ‘391 claims placing the importance of dimerization in the CAR provides motivation to modify dimerization domains for optimization of CAR using the dimerization properties as taught by Gurevich, Ostermeier and Klein.. One of ordinary skilled in the art would be motivated by analogous ease of using nuclear receptor dimers in the similar manner as ‘391 dimer switches which are very similar. One of ordinary skill in the art would be motivated by Ostermeier presentation of molecular switch using nuclear receptors such as estrogen receptor. One of ordinary skill in the art are aware as taught by Klein that estrogen receptor and LCoR dimerize and are controlled by ligand. The estrogen receptor and LCoR inherently have the same sequences as claimed. Gurevich et al. provides further support for the interaction of nuclear receptors with co-regulators. It would be obvious to use the agonists of estrogen receptor for the ‘391 claim small molecule dimerizer.
It would be obvious to one of ordinary skill in the art at the time of the filing date of the invention to modify the CAR as taught by ‘391 claims, Duchateau, Gurevich, Ostermeier, and Klein as discussed above by having a co-regulator with the length of up to 50 amino acids. One of ordinary skill in the art would be motivated to modify the size of the co-regulator to optimize the function of the CAR. One of ordinary skill in the art would also be motivated by the teaching of Ostermeier that size of insertion for the fusion molecules will vary depending on the desired particular state (column 12, lines 22-63). Gurevich teach the important box regions for the dimerization of the nuclear receptor to the co-regulator which are leucine rich regions (page 2 and 10).
Applicants request that the rejections be held in abeyance untila patentable subject matter has been identified. The rejection is maintained.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL D PAK whose telephone number is (571)272-0879. The examiner can normally be reached on flexible.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL D PAK/
Primary Examiner, Art Unit 1674