DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a divisional application (DIV) of U.S. Application Serial Number 16/705,966, filed 12/06/2019, which is a divisional application of U.S. Application Serial Number 13/695,459, filed 10/03/2013, which is a 371 of PCT/US2011/035223, filed 5/04/2011. This application claims benefit to U.S. Provisional Application Serial Numbers 61/447,905, filed 3/01/2011, 61/364,186, filed 7/14/2010 and 61/330,959, filed 5/04/2010. Claims 99-118 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statements submitted on 1/10/2025, 5/9/2025 and 3/30/2026 have been considered by the examiner.
Claim Objections
Claim 109 is objected to because of the following informalities:
Claim 109, line 5, recites “B-hydroxybutyrate” which should be “beta-hydroxybutyrate” or “β-hydroxybutyrate”.
Claim 109, line 7, recites “TNF-a”, which should be “TNF-alpha” or “TNF-α”. Appropriate correction is required.
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.
Claim 102 is 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.
Regarding claim 102, the claim recites storing an organ without freezing (lines 1-3), and recites “wherein the organ is contacted with a media comprising a supercoolant agent prior to cooling and freezing”; hence, it is unclear whether the organ is subjected to freezing or not; therefore, claim 102 is rejected under 35 U.S.C. 112(b) as being indefinite.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 99, 101-103, 105, 107-112 and 114-115 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Soltys et al., 2001 (NPL cite 350, IDS, 1/10/2025; herein “Soltys”).
Soltys teaches methods of assessing viability of preserved rat livers which have been contacted with supercoolant 2,3-butanediol (2,3-BD), cooled to -4ºC and storing the livers for 24 h at -4ºC without freezing (Abst.; p. 31, ‘Liver procurement’, ‘Subzero preservation’), i.e., further comprising storing the organ prior to assessing its viability, wherein storing the organ comprises cooling and storing the organ at a predetermined sub-zero temperature without freezing, and wherein the organ is contacted with a media comprising a supercoolant agent prior to cooling and freezing, wherein assessing viability of the organs comprises measuring the bile output, determining the energy charge by measuring ATP, ADP and AMP of the preserved livers (Abst.; p. 31, 'Rewarming and perfusion'; p. 32, ‘ATP determination’; Tables 1 and 2) and calculating hepatic oxygen consumption by measuring the inflow and outflow perfusate oxygen content (Abst.; p. 31, 'Rewarming and perfusion'; Table 1) during normothermic perfusion (p. 31, 'Rewarming and perfusion'; p. 32, ‘ATP determination’; Tables 1 and 2), i.e. a method of assessing viability of an organ, the method comprising: measuring at least one energy parameter of the organ; and determining a measure of viability of the organ as a function of at least one energy parameter, wherein the at least one energy parameter of the organ is indicative of a cellular energy status of the organ, wherein measuring the at least one energy parameter comprises measuring the cellular energy status during normothermic perfusion of the organ, measuring a level of a plurality of metabolites, measuring an oxygen consumption by the organ, measuring a level of gluconeogeneis of the organ, or measuring a nitrogen metabolism by the organ, wherein the at least one energy parameter of the organ is a level of adenosine triphosphate (ATP) in the organ, wherein at least one energy parameter of the organ comprises one or more of ATP, nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and glycogen, further comprising measuring an energy consumption by the organ; and determining the measure of viability as a function of: i) the at least one energy parameter, and ii) the energy consumption, wherein measuring the energy consumption by the organ comprises measuring a change in levels of a plurality of metabolites over a predefined period of time, wherein the change in levels of the plurality of metabolites comprises one or more of: oxygen uptake, carbon dioxide output, glucose output, lactate uptake, acetoacetate output, hydroxybutyrate output, urea output, ammonia uptake, alanine uptake, arginine uptake, ornithine uptake, asparagine uptake, aspartate uptake, cysteine output, glutamate output, glutamine uptake, glycine uptake, histidine uptake, praline uptake, serine uptake, methionine uptake, wherein measuring energy consumption comprises measuring a metabolic status of an organ by measuring one or more of: oxygen uptake, glucose levels, and nitrogen metabolism, wherein measuring the energy consumption by the organ comprises measuring a level of a plurality of metabolites, wherein the plurality of metabolites comprises bile and oxygen, and wherein measuring at least one energy parameter comprises measuring at least the level of ATP; anticipating claims 99, 101-103, 105, 107-111 and 115.
Soltys discloses adding taurocholate to the normothermic perfusion, after the sub-zero non-freezing (SZNF) preservation period, and assaying the extraction of taurocholate from the perfusion solution by the preserved livers, i.e., further comprising measuring the energy consumption by perfusing the organ with a metabolic flux assay perfusate and using a metabolic flux assay wherein perfusing the organ with the metabolic flux assay perfusate is performed at a temperature between about 20 °C and about 37 °C, anticipating claims 112 and 114.
Claims 99-101, 107-112 and 114-115 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Brasile, U.S. Patent 5699793 (cite A, attached PTO-892; herein “Brasile”).
Brasile teaches methods of preservation of organs comprising normothermic perfusion of the organs (Abst.). Brasile teaches that, as opposed to hyperthermic organ preservation, the normothermic perfusion allows the measuring of functional characteristics of the organ during preservation which can be compared to reference values to prospectively assess the functional characteristics of the organ posttransplantation (Abst.; col. 2, l. 62 - col. 3, l. 20; col. 3, l. 64 - col. 4, l. 3), i.e., comparing the measured functional characteristics, i.e., energy parameters and energy consumption, to a transplantability threshold and determining if the organ is suitable for implantation into a subject if the measured energy parameters are above the transplantability threshold.
Brasile teaches that the functional characteristics, i.e., energy parameters and energy consumption parameters, comprise oxygen consumption (col. 4, ll. 4-46), glucose utilization (col. 4, ll. 4-46), total protein (col. 4, ll. 4-10; col. 9, l. 26 - col. 12, l. 9), urine, i.e., urea (col. 4, ll. 4-10; col. 9, l. 26 - col. 12, l. 9), creatinine (col. 4, ll. 4-10; col. 9, l. 26 - col. 12, l. 9), bile (col. 4, ll. 11-17; col. 12, ll. 11-54), AST (col. 4, ll. 27-38; col. 13, l. 31 - col. 15, l. 20), ALP (col. 4, ll. 11-17; col. 12, ll. 11-54), sodium (col. 4, ll. 11-17; col. 12, ll. 11-54), potassium (col. 4, ll. 18-26; col. 12, l. 26 - col. 13, l. 30), total cholesterol (col. 4, ll. 11-17; col. 12, ll. 11-54) and insulin (col. 4, ll. 18-26; col. 12, l. 26 - col. 13, l. 30). Thus, Brasile teaches measuring at least one energy parameter of the organ; and determining a measure of viability of the organ as a function of at least one energy parameter, wherein the at least one energy parameter of the organ is indicative of a cellular energy status of the organ, comparing the at least one measured energy parameter to a transplantability threshold of an energy parameter of an organ; and determining if the organ is suitable for preservation and/or implantation into a subject if the at least one measured energy parameter is above the transplantability threshold, wherein measuring the at least one energy parameter comprises measuring the cellular energy status during normothermic perfusion of the organ, measuring a level of a plurality of metabolites, measuring an oxygen consumption by the organ, measuring a level of gluconeogeneis of the organ, or measuring a nitrogen metabolism by the organ, further comprising measuring an energy consumption by the organ; and determining the measure of viability as a function of: i) the at least one energy parameter, and ii) the energy consumption, wherein measuring the energy consumption by the organ comprises measuring a level of a plurality of metabolites, wherein the plurality of metabolites comprises oxygen consumption, glucose utilization, total protein, urea, creatinine, bile, AST, ALP, sodium, potassium, total cholesterol and/or insulin, anticipating claims 99-101, 107-111 and 115.
Brasile discloses making in-line measurements of constituents of the perfusate passing through the organ (col. 8, l. 40 - col. 9, l. 25) wherein metabolites such as creatinine (col. 10, ll. 15-37; Table 3) and/or glucose (Table 2) can be added to the perfusate and assayed for clearance by the organ, i.e., a metabolic flux assay conducted during normothermic perfusion by perfusing the organ with a metabolic flux assay perfusate and assaying the perfusate for creatinine and/or glucose anticipating claims 112 and 114.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 99, 101-105, 107-112 and 114-115 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Soltys.
The discussion of Soltys regarding claims 99, 101-103, 105, 107-112 and 114-115 set forth in the rejection above is incorporated herein.
Anticipation is the epitome of obviousness; hence, claims 99, 101-103, 105, 107-112 and 114-115 are rejected as prima facie obvious over Soltys.
Regarding claim 104, Soltys discloses that livers preserved at +4 °C in UW solution had 162 pg/mg protein of ATP, equivalent to 318 µmol ATP/g; livers preserved at -4 °C in UW solution + 10% 2,3-butanediol had 265 pg/mg protein of ATP, equivalent to 522 µmol ATP/g; and livers preserved at -4 °C in UW solution + 10% 2,3-butanediol and with type I antifreeze protein had 343 pg/mg protein of ATP, equivalent to 676 µmol ATP/g (Table 2); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that an organ predicted to be viable and suitable for transplantation would have an ATP level of at least 0.8 μmol/g of total protein; therefore, claim 104 is prima facie obvious.
Claims 99-101 and 106-118 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Brasile.
The discussion of Brasile regarding claims 99-101, 107-112 and 114-115 set forth in the rejection above is incorporated herein.
Anticipation is the epitome of obviousness; hence, claims 99-101, 107-112 and 114-115 are rejected as prima facie obvious over Brasile.
Regarding claim 106, Brasile discloses that viable organs preserved by her normothermic preservation method have near normal rates of metabolism wherein a near normal rate of metabolism is defined in Brasile as about 70%-90% of the range of normal rates of metabolism (col. 3, ll. 3-20); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that Brasile’s method is between about 50% and about 90% reliable at predicting the viability of the organ and/or a successful outcome of implantation of the organ into a subject; therefore, claim 106 is prima facie obvious.
Regarding claim 113, Brasile discloses that the perfusion solution comprises an oxygen carrier (col. 5, ll. 52-59) but does not specifically disclose that the perfusion solution comprises erythrocytes. Because erythrocytes, i.e., red blood cells, can function as oxygen carriers, a person of ordinary skill in the art at the time of filing would have found it obvious that erythrocytes can be the oxygen carrier in Brasile’s metabolic flux assays; therefore, claim 113 is prima facie obvious.
Brasile clearly teaches that the functional assays drawn to detecting and/or quantifying energy parameters, energy consumption parameters and compounds produced by the organ are used to determine the transplantability of the preserved organs (Abst.; col. 3, ll. 3-20; col. 3, l. 43 - col. 4, l. 50; col. 5, ll. 28-35) and specifically notes that failure to meet the reference values of the functional parameters indicates that the organ is damaged or unsuitable (glucose uptake - col. 8, ll. 8-14; oxygen consumption - col. 8, ll. 14-18); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to weight the various functional parameters, including the metabolic flux of oxygen, glucose and creatinine; the levels of protein, urea, creatinine, bile, AST, ALP, sodium, potassium, total cholesterol and/or insulin and oxygen consumption and glucose utilization, according to their average accuracies to give viability sub-scores and combine the sub-scores to determine the measure of viability; therefore, claims 116-118 are prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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