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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 11/24/2025 is acknowledged.
Claims 11-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/24/2025.
Claims 1-6, 8-10 and 35 are being examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The priority date is November 22, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 18, 2024 is being considered by the examiner. The signed IDS form is attached with the instant office action.
Drawings
The drawings were received on November 20, 2023. These drawings are acceptable.
Specification
The use of the term Normosol-R, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 35 is rejected under 35 U.S.C. 101 because the claimed composition is directed to a product of nature without significantly more. The first step of the eligibility analysis evaluates whether the claim falls within a statutory category (see MPEP 2106.03). Since the claim is directed to a composition comprising an axon treated with a nerve storage solution the claim is a composition of matter. Step 2A prong one of the analyses evaluates whether the claim is a judicial exception (see MPEP 2106.04). Because the claim states the nature-based products axons or tissue comprising axon the markedly different characteristics is performed by comparing the nature-based product limitation to its natural counterpart.
The claim recites the naturally occurring components which are animal cells/tissues. Animal cells and tissues are judicial exceptions and cannot be claimed. The claims also recite wherein the axon or tissue comprising axon is treated with a nerve storage solution according to claim 1. This treatment of the axon or tissue comprising axon does not change the axon or tissue comprising axon in any significant way to make it markedly different than an axon or tissue comprising axon in nature. The treatment appears to be a means of supplying electrolytes to the cell/tissue. Cells need these to survive and function. These cells and tissues are “treated” with these inside the animals where they reside. Merely removing them from an animal and supplying them with the components needed to help them survive is no different than what naturally takes place in nature. Adding these components to the cells/tissues does not make them have any additional properties because these properties are already found existing in those cells/tissues in their natural environment.
Step 2A prong two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. This judicial exception is not integrated into a practical application because the applicant is merely claiming an axon or tissue comprising an axon which has been “treated” with a specific solution comprising electrolytes.
Doing so would be implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
The claims do not integrate the judicial exceptions into a practical application because in this context, such integration for a claimed product would be a physical form of the specific practical application instead of a more general composition that is not so limited.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these components and their activity are already found naturally occurring in nature and the addition of an intended use does not impart any added benefit to the compounds or integrate the composition into a practical application.
Step 2 B evaluates whether the claim as a whole, amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05(b)). The claim merely amounts to the judicial exceptions which are cells/tissues from animals.
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 6, 9 and 35 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 6 recites the limitation "magnesium chloride hexahydrate" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites magnesium chloride but not magnesium chloride hexahydrate.
Claim 9 contains the trademark/trade name Normosol-R. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a solution and, accordingly, the identification/description is indefinite.
Claim 35 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. The claim recites “an axon or tissue comprising an axon treated with a nerve storage solution according to claim 1” which is confusing as there are no steps required for treatment and claim 1 is directed to a nerve storage solution, not a method of treating nerves. What are the actual treatment steps, administrations and length of administration or time for treatment, dosing, routes, etc. The claim is confusing and indefinite.
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 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.
The factual inquiries 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 1-6, 8-10 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over George D. ICU Medical (ifu0000172.pdf) included in file wrapper, and Alexa Roemmich et. al. (Ex vivo Whole-cell Recordings in Adult Drosophila Brain, Bio-Protocol Vol 8, Iss. 14, Jul 20, 2018) and Bittner (US20170252041A1).
ICU Medical teaches that NORMOSOL-R AND DEXTROSE- dextrose, sodium chloride, sodium acetate anhydrous, sodium gluconate, potassium chloride, and magnesium chloride and teaches that the solution is useful for replacement of losses of extracellular fluid (see page 1, description).
ICU Medical teaches that Normosol-R and 5% dextrose provides water and electrolytes with carbohydrate calories for replacement of acute extracellular fluid losses without disturbing normal electrolyte relationships. The electrolyte composition approaches that of the principal ions of normal plasma (extracellular fluid). The electrolyte concentration is approximately isotonic in relation to the extracellular fluid (approx. 280 mOsmol/liter) and provides a physiologic sodium to chloride ratio, normal plasma concentrations of potassium and magnesium and two bicarbonate alternates, acetate and gluconate. Dextrose provides minimal calories and renders the solution hypertonic. (see page 2, last para.).
Sodium chloride in water dissociates to provide sodium (Na+) and chloride (Cl‾) ions. Sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl‾) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in the red blood cells. The distribution and excretion of sodium (Na+) and chloride (Cl‾) are largely under the control of the kidney which maintains a balance between intake and output.
Potassium chloride in water dissociates to provide potassium (K+) and chloride (Cl‾) ions. Potassium is the chief cation of body cells (160 mEq/liter of intracellular water). It is found in low concentration in plasma and extracellular fluids (3.5 to 5.0 mEq/liter in a healthy adult and child over 10 days old; 3.5 to 6.0 mEq/liter in a child less than 10 days old). Potassium plays an important role in electrolyte balance.
Normally about 80 to 90% of the potassium intake is excreted in the urine; the remainder in the stools and to a small extent, in the perspiration. The kidney does not conserve potassium well so that during fasting or in patients on a potassium-free diet, potassium loss from the body continues resulting in potassium depletion.
Magnesium chloride in water dissociates to provide magnesium (Mg++) and chloride (Cl‾) ions. Magnesium is the second most plentiful cation of the intracellular fluids. It is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability. Normal plasma concentration ranges from 1.5 to 2.5 or 3.0 mEq per liter. Magnesium is excreted solely by the kidney at a rate proportional to the plasma concentration and glomerular filtration.
Sodium acetate provides sodium (Na+) and acetate (CH3COO‾) ions, the latter anion (a source of hydrogen ion acceptors) serving as an alternate source of bicarbonate (HCO3‾) by metabolic conversion in the liver. This has been shown to proceed readily even in the presence of severe liver disease. Thus, acetate anion exerts a mild systemic antiacidotic action that may be advantageous during fluid and electrolyte replacement therapy.
Sodium gluconate provides sodium (Na+) and gluconate (C6H1107‾) ions. Although gluconate is a theoretical alternate metabolic source of bicarbonate (HC03‾) anion, a significant anti acidotic action has not been established. Thus, the gluconate anion serves primarily to complete the cation-anion balance of the solution.
Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).
ICU Medical teaches “each 100 mL of Normosol-R and 5% Dextrose Injection contains dextrose 5 g; sodium chloride 526 mg; sodium acetate, anhydrous 222 mg; sodium gluconate 502 mg; potassium chloride 37 mg; magnesium chloride, hexahydrate 30 mg; pH adjusted with hydrochloric acid. The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) (see first page, 2nd para.) and teaches the pH to be at 6.5 (see table).
ICU Medical does not teach the osmosality at 205-255 mOsm L.
Bittner teaches A method of treating a mammal with a nerve in need of repair comprising the steps of: a) applying a hypotonic, calcium-free saline solution to said nerve for a first period of time (see claim 23) and In some configurations, the method further comprises the steps of:[0064] delivering at least one hypotonic calcium-free solution to the nerve; and [0065] evacuating the at least one hypotonic calcium-free solution away from the nerve before delivering the at least one of the antioxidant and the inhibitor of membrane sealing.
Bittner teaches “furthermore, these data also indicate that the above sequence advantageously improves recovery time and nerve function compared to microsutures, specifically by a factor of up to two and 40 percent in four months, respectively (see 0053).
Bittner teaches the hypotonic calcium free solution to comprise of sodium chloride, potassium chloride, sodium bicarbonate, and/or dextrose (see claim 27) and teaches the solution to comprise of nerves which comprise of axons (see claim 1, 0036, 0053).
Roemmich’s general disclosure pertains to whole-cell recordings of Drosophilia Brain (see abstract).
Roemmich teaches for taking neuronal whole-cell recordings that osmolarity is crucial to the success and teaches the external solutions should be adjust pH 7.2 with NaOH and adjust osmolarity to 250-255 mOsm L-1. External solution can be kept at 4 °C for a week (see page 12, external solutions 2 and 3).
Therefore it would have been obvious to persons having skill in the art before the effective filing date to create a nerve storage solution comprising of sodium chloride, sodium acetate anhydrous, sodium gluconate, potassium chloride, and magnesium chloride because ICU Medical teaches each component being useful for supplying extracellular cations to cells which are in need of electrolytes. Bittner teaches of calcium-free solutions for nerve cells which comprise of similar electrolytes and teaches wherein the solutions are calcium-free and hypotonic. One would rely on Bittner for the information of keeping the solution hypotonic and free of calcium along with the knowledge presented by ICU Medical and Roemmich. Neither pieces of art teach of calcium being in solutions and Roemmich and Bittner teach keeping the solution hypotonic. Roemmich teaches nerve cells can survive in hypotonic solutions at 250-255 mOsm L for up to a week when kept at 4 degrees. Persons having ordinary skill could rely on these pieces of art to selectively use Normosol-R to replenish extracellular electrolytes and without using calcium. ICU Medical teaches that sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl‾) has an integral role in buffering action. Potassium is the chief cation of body cells; magnesium is the second most plentiful cation of the intracellular fluids. It is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission; sodium acetate anion exerts a mild systemic anti acidotic action that may be advantageous during fluid and electrolyte replacement and sodium gluconate anion serves primarily to complete the cation-anion balance of the solution. Roemmich teaches that neurons can survive in hypotonic solutions at 250-255 mOsm L for up to a week. Therefore creating a solution which comprises of Normosol-R which would comprise each sodium chloride, sodium acetate anhydrous, sodium gluconate, potassium chloride, and magnesium chloride and adjusting the mOsm to be at 250-255 mOsm L. would be obvious given the relied upon art.
Optimizing the amount of the sodium chloride to be at 526 mg/100ml, sodium acetate at 222mg/100ml, sodium gluconate at 502mg/100ml, potassium chloride at 37mg/100ml and magnesium chloride, or optimizing the sodium about 140 mEq, potassium about 5 mEq, magnesium about 3 mEq, chloride about 98 mEq, acetate about 27 mEq, and gluconate about 23 mEq, would have been obvious because each of the electrolytes has been shown to have specific functional activities and contribute to the overall osmolality of the storage solution.
Conclusion
No claims are allowed.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655