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 status
Claims 1-9 is/are currently pending and is/are under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in CN on 3/20/2021. It is noted, however, that applicant has not filed a certified copy of the CN202110298828.X application as required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Drawings
The drawings are objected to because the y-axis in Figure 23 is incorrectly labelled as “Reactive Expression” when it should be “Relative Expression”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The abstract of the disclosure is objected to because of undue length of 170 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
(1) The specification uses an abbreviation “HPL” as a culture medium in [0031, 0086, 0090, 0120, 0136, 0138, 0139]. HPL is not a known culture medium is the art. The specification does not disclose what HPL culture medium is or the full-form of the abbreviation HPL.
(2) In [0122], the specification states “5 cells/ml with the preservation solution”. This appears to be incorrect since it is likely that 5x105 cells/ml were mixed with the preservation solution based on disclosure in para [0121].
Appropriate correction is required.
Claim Objections
Claims 2 and 4 are objected to because of the following informalities: Claims recite “sulfite antioxidant-free compound amino acid injection 14AA, 14AA-SF”. Abbreviations such as “14AA-SF” should be provided within brackets following the full-form “sulfite antioxidant-free compound amino acid injection 14AA”. Use of comma in this instance is inappropriate.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-9 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 1 recites “a ratio of (1-5) ml: (0.01-1) g: (0.1-1) g”. Ratios do not comprise numbers with different units. Additionally, it is unclear how to interpret meets and bounds of the recited ration since each number is a range. Claim 3 recites the same elements as claim 1 in lines 3 and 4 but instead of using a ratio, recites a range of amount for each of the elements. For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “consisting of 1-5 ml of a compound amino acid injection, 0.01-1 g of L-glutamine and 0.1-1 g of anhydrous glucose
Regarding claim 2, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of compact prosecution, the claim(s) 2 is/are interpreted as wherein the limitation recited after “preferably” is optional. This provides the broadest reasonable breadth to the claim. Additionally, claim(s) 2 is/are also interpreted as wherein the limitation recited after “preferably” is required.
Regarding claim 3, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of compact prosecution, the claim(s) 3 is/are interpreted as wherein the limitation recited after “preferably” is optional. This provides the broadest reasonable breadth to the claim. Additionally, claim(s) 3 is/are also interpreted as wherein the limitation recited after “preferably” is required.
Regarding claims 5 and 6, the phrase "preferably" renders these claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of compact prosecution, the claim(s) 5 and 6 is/are interpreted as wherein the limitation recited after “preferably” is optional. This provides the broadest reasonable breadth to the claim. Additionally, claim(s) 5 and 6 is/are also interpreted as wherein the limitation recited after “preferably” is required.
Claims 5 and 6 are directed to “Application of the cell preservation solution according to claim 3” in the manufacture/preservation of a mesenchymal stem cell preparation, NK cell preparation, or CART cell preparation. It appears that the claims are methods using the product of claim 3. Neither of these claims set forth any active step using the product of claim 3 in manufacture or preservation. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).
Claims 2-9 is/are rejected due their dependence on claim 1 because they do not clarify the 112b issue noted with claim 1.
Claims 4-9 is/are rejected due their dependence on claim 3 because they do not clarify the 112b issue noted with claim 3.
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 5 and 6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because although the claims appear to be directed methods/processes (one of the statutory categories), they recite no active method step(s).
"Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 "). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967), the Board held the following claim to be an improper definition of a process: "The use of a high carbon austenitic iron alloy having a proportion of free carbon as a vehicle brake part subject to stress by sliding friction." In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), the district court held the following claim was definite, but that it was not a proper process claim under 35 U.S.C. 101: "The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid."
The claimed recitation of an intended use of a composition, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101.
Claim Interpretation
The term “compound amino acid injection” is recited in the claims. The specification does not provide a definition for this term nor does it identify the amino acids that are required to be included in the claimed “compound amino acid injection”. Various “compound amino acid injections” are commercially available and used in the art however a clear definition or standard is not established in the art. For example, Shi et al (Front. Nutr., June 2022, Volume 9, Article 880256) states that “At present, there are many formulations of balanced amino acids for injection in China, produced by numerous manufacturers, with variations in the content and price. The total AA content, as well as the contents of the different EAAs, are related to the safety, effectiveness, and economy of these clinical medications” (page 2, col. 2, para 1). Wu et al (World Journal of Surgical Oncology (2015) 13:336) teach a “compound amino acid injection” compositions compounded to comprise various amino acids (Tables 4 and 5). Since “compounds amino acid injections” can comprise any type of and any number of amino acids, the term “compound amino acid injection” is broadly interpreted to be a solution comprising at least one amino acid of any type.
The term “compound amino acid injection 14AA” is recited in the claims. The specification does not provide a definition for this term nor does it identify the amino acids that are required to be included in the claimed “compound amino acid injection”. It is understood that compound amino acid injection 14AA comprises at least 14 amino acids.
The term “compound electrolyte injection” is recited in the claims. The specification does not provide a definition for this term nor does it identify the electrolytes that are required to be included in the claimed “compound electrolyte injection”. It is understood that compound electrolyte injection is a solution that comprises electrolytes i.e. necessary salts, such as NaCl, KCl etc.
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.
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.
Claim(s) 1, 3, 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al (CN 108651442 A, 2018-10-16; Machine translation generated from PE2E SEARCH provided in the PTO-892. Citations in the rejection below are from the Machine translation) in view of Zhang et al (CN 109381457 A, 2019-02-26; Machine translation generated from PE2E SEARCH provided in the PTO-892. Citations in the rejection below are from the Machine translation).
Regarding claims 1, 3, Cheng teaches a cell preservation solution comprising human serum albumin (HSA), sodium lactate Ringer injection (=compound electrolyte injection), page 4-para 2), essential and non-essential amino acids (=compound amino acid injection), L-glutamine and glucose (=anhydrous glucose because Cheng teaches glucose powder amount of 1-50mg/ml; see “glucose is 0.1%-5%mg/ml” on page 2-para 5; Note: 1%mg/ml = 10mg/ml) (Abstract).
Cheng uses %mg/ml and %ml/ml units for some components. Note: 1%mg/ml = 10mg/ml = 1g/100ml; and 1%ml/ml = 0.01ml/ml = 1ml/100ml.
Regarding the amount of HSA, Cheng teaches 0.5%-5%mg/ml which equals 0.5-5g/100ml (page 2, para 5). The claim does not recite the amount or concentration of HSA in the 5-15ml HSA included in the 100ml cell preservation solution. An ordinary artisan preparing a stock solution of HSA to be added to the cell preservation solution could generate a HSA stock such that it results in 0.5-5g HSA being added, as taught by Cheng, in a volume of 5-15ml, as claimed, to the final 100ml volume of cell preservation solution. Additionally, the specification discloses the stock concentration of HSA to be 10g/50ml [0073]. Thus, 5-15ml of 10g/50ml HSA is equal to 1-3g of HSA included in 100ml cell preservation solution. Thus, in teaching HSA at 0.5-5g, Cheng teaches the narrower range of 1-3g or as claimed 5-15ml.
Regarding the amount of compound electrolyte injection, Cheng teaches 86%-98%ml/ml which equals 86-96ml/100ml which overlaps the claimed 80-90ml (page 2, para 5). MPEP 2144.05 states “"[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). ”. In the instant case, in teaching a slightly broader range of 86-96ml, Cheng renders obvious the slightly narrower range of the claim i.e. 80-90ml.
Regarding compound amino acid injection, Cheng teaches “lysine, tryptophan, phenyl alanine, methionine, threonine, isoleucine, leucine, valine, glutamic acid, alanine, glycine, aspartic acid, cysteine, proline, serine and tyrosine” as amino acids and identifies this solution as “compound amino acids” in some embodiments (page 2, paras 6, 7, 8; page 4, para 7; Examples 3-5). Since Cheng’s compound amino acid injection comprises at least 14 amino acids, it is a compound amino acid injection 14AA.
Regarding the amount of compound amino acid injection, Cheng teaches 1%-10%ml/ml which equals 1-10ml/100ml and overlaps the claimed 1-5ml/100ml(page 2, para 5). See guidance from MPEP 2144.05 regarding overlapping ranges. In the instant case, in teaching a slightly broader range of 1-10ml/100ml, Cheng renders obvious the slightly narrower range of the claim i.e. 1-5ml/100ml.
Regarding the amount of L-glutamine, Cheng teaches 1-10mM glutamine which equals 0.014-0.146g/100ml (=claimed 0.01-1g/100ml; page 2, para 5).
Regarding the amount of glucose, Cheng teaches 0.1%-5%mg/ml which equals 0.1-5g/100ml and overlaps the claimed 0.1-1g/100ml(page 2, para 5). See guidance from MPEP 2144.05 regarding overlapping ranges. In the instant case, in teaching a slightly broader range of 0.1-5g/100ml, Cheng renders obvious the slightly narrower range of the claim i.e. 0.1-1g/100ml.
Regarding claims 5-7, Cheng teaches use of their cell preservation solution for preserving mesenchymal stem cells (MSC), including preserving at 4°C, wherein the solution comprises MSCs (Abstract, Example 2-4; Claim 1).
Regarding claim 1 and 2, Cheng does not explicitly teach a composition consisting of (closed transitional phrase; see MPEP 2111.03) only compound amino acid injection, L-glutamine and anhydrous glucose.
Additionally Cheng does not teach a sulfite antioxidant-free compound amino acid injection, as recited in claims 2-4.
Regarding a composition consisting of only compound amino acid injection, L-glutamine and anhydrous glucose, Cheng teaches a composition comprising the “composition for producing a cell preservation solution”, teaching each of its components and concentration/amounts (Abstract, page 2-para 5). Cheng does not teach first mixing only compound amino acid injection, L-glutamine and anhydrous glucose such that a composition consisting of only these components is first produced and then these are mixed with the rest of the ingredients to form the final cell preservation solution. However, order of mixing components such that a sub-combination of components is produced first resulting in a product that comprises a sub-combination of components is obvious. In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.). See MPEP 2144.04(IV)(C). An ordinary artisan routinely mixes components to make solutions. An ordinary artisan mixing components taught Cheng could mix the components such that a sub-combination of components, as claimed in claim 1 or 2, is produced. ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A). In the instant case, there is not even evidence of an improved product. Additionally, even the instant specification does not teach only the subcombination of claims 1 and 2 and a separate utility of this claimed subcombination. Therefore, in teaching a composition comprising the “composition for producing a cell preservation solution”, teaching each of its components and concentration/amounts, Cheng renders obvious a composition consisting of only these components, as claimed in claim 1.
Regarding sulfite antioxidant-free compound amino acid injection, Zhang teaches a sulfite antioxidant-free compound amino acid injection comprising 14 amino acids (=claimed 14AA-SF; Abstract). Zhang teaches because amino acid solutions easily oxidize, antioxidants are added to them but use of traditional antioxidants such as sulfites have negative effects on human body and thus its use in medicine is limited (page 2, para 6 and 7). Zhang teaches a stable compound amino acid injection without sulfite (Summary of Invention, page 3).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the stable compound amino acid injection without sulfite taught by Zhang in Cheng’s cell preservation solution. An artisan would be motivated to make such a substitution because it would make the compound amino acid injection component of Cheng’s cell preservation solution stable and of low hazard to humans. An ordinary artisan would reasonably expect to make such a substitution because Zhang teaches the composition of their compound amino acid injection on page 3 and an artisan would substitute this composition in Cheng’s cryopreservation solution. Additionally, Zhang teach methods to make compound amino acid injection in which oxygen content is constantly monitored and if oxygen amount increases in the solution then it is replaced with nitrogen, thus removing the need for an anti-oxidant (page 5, para 8,9). Thus, an ordinary artisan could reasonably produce a compound amino acid injection with any amino acids without sulfite-antioxidant using Zhang’s method.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Claim(s) 8, 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cheng in view of Zhang as applied to claim 3 above, and further in view of Ge et al (CN 104542578 A, 2015-04-29; Machine translation generated from PE2E SEARCH provided in the PTO-892. Citations in the rejection below are from the Machine translation) and Basar et al (Hematology Am Soc Hematol Educ Program (2020) 2020 (1): 570–578.)
The teachings of Cheng and Zhang as detailed in the U.S.C. 103 rejection above are relied upon for the instant rejection.
Cheng teaches the use of their cell preservation solution for preserving mesenchymal stem cells (MSC), including preserving at 4°C, wherein the solution comprises the cells i.e. MSCs (Abstract, Example 2-4; Claim 1).
Cheng does not teach the use of their cell preservation solution for preserving NK or CAR-T cells, including preserving at 4°C, wherein the solution comprises these cells.
Ge teaches a cell preservation solution comprising albumin, glucose, compound electrolyte injection and compound amino acid injection, similar to Cheng (Abstract). Ge teaches use of cell preservation solutions for cells used in cell therapy such as MSCs, same as Cheng, but also the same solution for preserving other cells used in cell therapy such as immune cells, for e.g. CIK-cells which are NK-cell like T cells [0003-004, 0045-0066].
Basar teaches both NK-cells and CAR-T cells as immune cells commonly used in cell therapy (Learning objectives, Table 1).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the cryopreservation solution of Cheng and Zhang to preserve other cells used in cell therapy such as NK and CAR-T immune cells. An ordinary artisan would be motivated to use Cheng’s cryopreservation solution to preserve NK and CAR-T immune cells because these cells are being widely used in human cell therapy, as taught by Bassar, and thus require preservation between uses. An ordinary artisan would reasonably expect to preserve NK and CAR-T immune cells in Cheng’s cryopreservation solution because Ge teaches that cryopreservation solutions for MSCs are also applicable to immune cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632