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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 17, 2025 has been entered.
Status of the Claims
Claims 1-18 were originally filed August 23, 2021.
The amendment received April 13, 2022 amended claims 5, 7-11, 13, and 15-18 and cancelled claim 14.
The amendment received May 23, 2024 canceled claims 1-12, amended claim 13, and added new claims 19-24.
The amendment received December 12, 2024 amended claim 13. Please note: claims 16-18 and 20-24 have improper status identifiers.
The amendment received September 17, 2025 amended claim 13. Please note: claims 16-18 and 20-24 have improper status identifiers.
Claims 13 and 15-24 are currently pending.
Claims 13, 15, and 19 are currently under consideration.
Please note: it is unclear how the amendment to the claims received September 17, 2025 advances prosecution (see the REMARKS section of the response received September 17, 2025) when the amendment broadens the scope of independent claim 13 (i.e. intravenous administration was deleted, thus the claims now encompass any administration method).
Election/Restrictions
Applicants elected, without traverse, Group II (now claims 13 and 15-24) in the reply filed on May 23, 2024. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicants elected, without traverse, SEQ ID NO: 1, liver disease, and acute liver injury or failure is treated as the species in the reply filed on May 23, 2024. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 16-18 and 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Priority
The present application is a 371 (National Stage) of PCT/US2020/020081 filed February 27, 2020 which claims the benefit of 62/811,135 filed February 27, 2019.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Rejection
The provisional rejection of claims 13, 15, and 19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 17/433,011 in view of Chamuleau et al. WO 2010/123357 published October 28, 2010 is withdrawn in view of the ABN of the application.
New Rejection
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 13, 15, and 19 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 13 is drawn to a method for treating or preventing acute liver failure (ALF) comprising administering to a subject a composition comprising a CPS1 polypeptide having at least 90% identity to all or a portion of SEQ ID NO: 1 wherein the CPS1 polypeptide exhibits a cytokine-like activity of a CPS1 polypeptide of SEQ ID NO: 1. The invention as claimed encompasses all portions of SEQ ID NO: 1. The claimed invention states that the CPS1 polypeptide exhibits a cytokine-like activity of a CPS1 polypeptide of SEQ ID NO: 1. The claimed invention does not include any structural information regarding the “portions” (i.e. no indication of which portions would be able to treat or prevent ALF; the “portion” also does not require exhibiting a cytokine-like activity of a CPS1 polypeptide of SEQ ID NO: 1). In addition, the claimed invention does not include any structural information regarding the “portion” (e.g. common core structure necessary for function, etc.).
The specification teaches SEQ ID NOs: 2-8 (“portions” of SEQ ID NO: 1), but the specification is silent with regard to the function or therapeutic benefit of SEQ ID NOs: 2-8. In addition, the specification only teaches the therapeutic benefit of the complete SEQ ID NO: 1 (100% identity and the same length; see pages 52-53 of the originally filed specification and Figures 5A-5H, 6A-6K, 17, and 18). However, the claimed invention does not include the structural limitation of what “portion” of SEQ ID NO: 1 would have the same therapeutic benefits as full-length SEQ ID NO: 1. Therefore, one skilled in the relevant art would not reasonably conclude that the Applicants had possession of the invention as claimed since the structural limitation of the “portion” is not included in the claimed invention.
See Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "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 page 1116.).
With the exception of full-length SEQ ID NO: 1 as disclosed by the specification, the skilled artisan cannot envision the method of claim 13. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class wherein the specification provided only the bovine sequence.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Maintained Rejections and/or Modified* Rejections
*wherein the modification is due to amendment
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.
Claims 13, 15, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chamuleau et al. WO 2010/123357 published October 28, 2010.
For present claims 13, 15, and 19, Chamuleau et al. teach methods of treating a subject with acute liver failure and/or liver disease via utilizing a bioartificial liver system (BAL) which expresses human CPS1 at levels at least 20% of a normal liver and more preferably 40%, 50%, 75%, or 90% thereby administering human CPS1 to the subject (please refer to the entire specification particularly the abstract; pages 1, 3, 12, 17, 18, 21, 22, 25, 30; Tables 2 and 6). Chamuleau et al. teach utilizing inlets and outlets to carry the subjects blood to and from the BAL system (i.e. intravenous; please refer to the entire specification particularly Figures 1 and 2; pages 1, 2, 12, 22, 24, 25; Tables 2 and 6).
Regarding SEQ ID NO: 1 (i.e. human CPS1), "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." See Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. See In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
Therefore, the teachings of Chamuleau et al. anticipate the presently claimed method.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Chamuleau et al. for claims 13, 15, and 19 were considered but are not persuasive for the following reasons.
Applicants contend that Chamuleau et al. do not teach secretion of CPS1 from liver cells. Applicants point to page 8, lines 25-26 to show that CPS1 is continuously secreted to bile from the liver
Applicants’ arguments are not convincing since the teachings of Chamuleau et al. anticipate the method of the instant claims. Chamuleau et al. teach utilizing inlets and outlets to carry the subjects blood to and from the BAL system (please refer to the entire specification particularly Figures 1 and 2; pages 1, 2, 12, 22, 24, 25; Tables 2 and 6).
At page 8, lines 25-26 of the originally filed specification, it is shown that CPS1 is continuously secreted to bile from the liver. Thus, CPS1 is secreted from liver cells (e.g. as opposed to a non-secreted polypeptide with a transmembrane domain, a polypeptide retained in the cell, etc.). See also Park et al., 2019, Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury, PNAS, 116(18): 9125-9134.
Thus, the BAL system with liver cells taught by Chamuleau et al. would secrete CPS1.
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 13, 15, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Khoja et al., 2018, Conditional Disruption of Hepatic Carbamoyl Phosphate Synthetase 1 in Mice Results in Hyperammonemia without Orotic Aciduria and Can be corrected by Liver-Directed Gene Therapy, Mol Genet Metab, 124(4): 243-253 and Chamuleau et al. WO 2010/123357 published October 28, 2010.
For present claims 13 and 15, Khoja et al. teach methods of treating complications of acute liver failure (i.e. hyperammonemia) via administering gene therapy which expresses CPS1 (please refer to the entire reference particularly the abstract; Materials and Methods; pages 10-12; Discussion). Khoja et al. teach intravenous administration of the vectors (see section 2.1.10).
While Khoja et al. teach mice (subject) and murine CPS1, Khoja et al. does not teach human CPS1.
For present claims 13, 15, and 19, Chamuleau et al. teach methods of treating a subject with acute liver failure and/or liver disease via utilizing a bioartificial liver system (BAL) which expresses human CPS1 at levels at least 20% of a normal liver and more preferably 40%, 50%, 75%, or 90% thereby administering human CPS1 to the subject (please refer to the entire specification particularly the abstract; pages 1, 3, 12, 17, 18, 21, 22, 25, 30; Tables 2 and 6). Chamuleau et al. teach utilizing inlets and outlets to carry the subjects blood to and from the BAL system (i.e. intravenous; please refer to the entire specification particularly Figures 1 and 2; pages 1, 2, 12, 22, 24, 25; Tables 2 and 6).
Regarding SEQ ID NO: 1 (i.e. human CPS1), "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." See Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. See In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
The claims would have been obvious because the substitution of one known element (i.e. utilizing murine CPS1 in a mouse) for another (i.e. utilizing human CPS1 in a human) would have yielded predictable results (i.e. treatment of a condition associated with acute liver failure) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Intravenous administration of polypeptides is exceedingly common in the prior art. See Ozaki et al., 1994, Enzyme Protein, 48(4): 213-221 (abstract only). The claims would have been obvious because a particular known technique (i.e. intravenous administration of polypeptides including CPS1) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Khoja et al. and Chamuleau et al. for claims 13, 15, and 19 were considered but are not persuasive for the following reasons.
Applicants contend that Khoja et al. do not teach acute liver failure.
Applicants’ arguments are not convincing since the teachings of Khoja et al. and Chamuleau et al. render the method of the instant claims prima facie obvious.
Khoja et al. teach hyperammonemia which is a complication of acute liver failure. See also Kumar et al., 2012, Persistent Hyperammonemia is Associated with Complications and Poor Outcomes in Patients with Acute Liver Failure, Clinical Gastroenterology and Hepatology, 10: 925-931.
Chamuleau et al. teach acute liver failure.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Future Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER D STEELE whose telephone number is (571)272-5538. The examiner can normally be reached M-F 8-5.
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/AMBER D STEELE/Primary Examiner, Art Unit 1658