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 .
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract employes legal phraseology such as the term “comprise”. 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).
Claim Interpretation
Content of Specification
(k) CLAIM OR CLAIMS: See 37 CFR 1.75 and MPEP § 608.01(m). The claim or claims must commence on a separate sheet or electronic page (37 CFR 1.52(b)(3)). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation. There may be plural indentations to further segregate subcombinations or related steps. See 37 CFR 1.75 and MPEP 608.01(i)-(p).
The claimed invention is defined by the positively claimed elements, the structural elements listed on separate indented lines listed in the body of the claim after the transitional phrase, “comprising”.
A claim is only limited by positively claimed elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims”. MPEP 2115 Material or Article Worked Upon by Apparatus.
A claim is only limited by positively claimed elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims”. MPEP 2115 Material or Article Worked Upon by Apparatus.
As to claim 1, it is noted that the device and closed vial are one in the same. Furthermore, it is noted that the phrase “unit of use” and “cryogenic” do not provide for any structural element of the vial. The invention is a closed vial (container) containing stem cells.
It is noted that the apparatus claims mention a cell container, air vent, fill tube (claim 3), fill port (claim 6-7), and a cell delivery device (claim 7). However, none of such are positively claimed, listed as structural elements of the device. All of such are considered as materials or articles intended be, can be worked upon and/or used with the device.
It is noted that the term “or” provides for alternative options which are not requirements. Only one alternative is required.
It is noted that “air vent” is not defined in the claims as being any specific structure. Any structure (hole, opening, port, etc.) through which air can pass can be considered as an air vent.
The term “fill” in “fill tube”, “fill port”, and “fill attachment piece”, “fill is directed to the intended use of such tube, port, and attachment piece.
It is noted that the term “cell” in “cell container” and “cell delivery device” is directed to intended use. No cells are claimed as being present the container.
As to claim 16, it is noted that there is no step that requires attaching a cell delivery device to the fill attachment piece. The cell delivery device is not required to be present.
It is noted that “a subject” is not specifically defined in the claims
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 1-24 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.
As to claims 1, 4, 10, 12, 19, it is unclear what is meant by “per ml”, “cells/ml”, and “24×10.sup.6/ml” (claim 10) because the claim does not clearly provide for such. It is presumed that such is intended to refer to stem cell concentration and cell concentration (in claim 10). However, it is unclear how such concentrations exist because the claims do not require the stem cells and cells to be located within any liquid solution.
Claims 2-9 and 11-24 are rejected via dependency upon a rejected claim.
As to claim 2, it is unclear if the cell container is intended to be an element of the device. As presently drafted, the cell container is not positively claimed as an element of the device because reciting that a prior claimed tube is connected to a cell container (not previously positively claimed) does not require the cell container to be an element of the device.
As to claim 3, it is unclear what the term “volume” references because it is unclear if such refers to the maximum volumetric capacity of the vial or a volume of an unspecified contents of the volume.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation of 1-5 ml, and the claim also recites further ranges 1-2 ml, 1.45-1.50 ml, 4-5 ml, and 4.05-4.96 ml. which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
As to claim 4, it is unclear what is being referenced by “cells/ml”. It is presumed to be intended to be “stem cells/ml”. See also prior rejection above directed to such.
It is unclear what is structurally required by claim 5 because it is unclear if the device is intended to comprise any of the structures recited in the claim because the does not state the device comprises any of such. As presently drafted, none of the structures are positively claimed as elements of the device. Furthermore, even if the term “comprises” was present after “claim 1”, it is noted that the air vent and fill tube would not be considered as elements of the invention because as stated above relative to claim 2 reciting that a positively claimed structure is connected to structures not previously positively claimed does not require the latter structures to be elements of the device. This is also applicable to the “fill port” recited in claim 6.
Furthermore, even if the structures in the claim were positively claimed, it is unclear what is the structural nexus, connectivity of such structures (the cell container and further recited structures in claim 5) to the vial of claim 1 because the claim does not provide for such. A list of structures not required to be structurally connected does not define a single device.
As to claim 5, it is unclear what the term “each” references because the claim does not clearly state such.
The term “adjacent” in claim 5 is a relative term which renders the claim indefinite. The term “adjacent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term does not provide for any clear and definitive structural connectivity of the proximal surface and top end nor any definite relative distance between such. What may be considered as “adjacent” to one person may be considered as such to another and vice versa.
It is unclear what is further structurally required by claims 6-9 because the claims are directed to structures not previously positively claimed as elements of the device. See prior rejection above directed to claim 5.
As to claim 10 see prior applicable rejection above. It is presumed that the phrase “the cells” refers to the ABCB5-positive cells. See also claims 12 and 20-21. Furthermore, it appears as if claim 10 should read as “preparing a pooled population comprising ABCB5-positive cells by concentrating the ABCB5-positive cells…. However, it is unclear how such cells can be concentrated because such cells are not claimed as being required to be located within any liquid solution (nor in any other substance). Furthermore, it is unclear how “resuspending” can be performed because the cells have not been previously established, required for the cells to initially be suspended in anything. It is unclear what the cells are intended to be suspended and resuspended in because the claim does not provide for such.
As to claim 5, it is unclear what is further required by the phrase “optionally aliquoting a unit sample of cells from the pooled sample and transferring the unit sample to a fill tube (3) through a fill port (2) of a closed system cryogenic vial (1), and the unit sample is transferred into the cell container (6) to produce a unit dose of a therapeutic cell solution (7)” because the phrase is directed to options as indicated by the term “optionally”. It presumed that “a unit sample of cells” is intended to be “a unit sample of the ABCB5-positive cells”. If so, the claim should clearly recite such.
Options are not requirements. Therefore, that recited in phrase is not required to be performed and does not define the method. The phrase is negligible and therefore, the only required step is the preparing step. It is unclear how if the method only requires the preparing step that a unit does of a therapeutic cell solution is produced as recited in the preamble. The preparing step makes no mention of any such of the therapeutic cell solution. As noted above, the cells are not required to be located/suspended in any liquid solution and such cells and solution are not required to be located in any container. Therefore, although the transferring is an option, it is unclear what the unit sample is required to be transferred from because the claim does not provide of such.
Claim 10 recites the limitation "the cell container" in the next-to-last line. There is insufficient antecedent basis for this limitation in the claim.
It is unclear what is further required by claims 11 and 13-21 because the claims are directed to the “optionally” phrase of claim 10 that is not a requirement.
In claim 11 it is unclear what the angling in the first line is relative to because the claim does provide for such. See also claim 14 that does not provide for any relative basis for what is considered as 90 degrees (relative to what). Furthermore, the claim appears to be redundant because claim 10 recites “angling the vial to an upright position” (90 degrees).
As to claim 11, it is unclear what is “a sterility testing sample” because the claim does not clearly define such. It is unclear what is the nexus of such sterility testing sample to the therapeutic cell solution and where such testing sample is located such that it can pass back in into the sample tube. It is noted that there is no mention of any sterility testing sample initially passing from anything into the fill tube such that it can pass back into the sample tube. Furthermore, it is noted that the claim does not provide for any sterility testing of any sample of anything.
The term “about” in claims 12-14 and 18-19 is a relative term which renders the claims indefinite. The term “about” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what variances from the exact values, values other than recited exact values are considered as being “about” the recited values because the claim does not provide for such. Values that may be considered about the recited values by one person may not be considered as such by another and vice versa.
As to claims 20-21, see prior rejection above directed the “optionally” clause. In addition to such, it is unclear how the claims can require “thawing” because there is no prior requirement for the vial nor cells and cell solution to be frozen.
Furthermore, it is unclear what is required to be done to be considered as “reconstituting” and how any “reconstituting” because no initial constituting of any cells and unconstituting of cells are required to performed such that any reconstituting can be performed.
As to claim 22, the claim should read as “…the device of claim 1….”
As to claim 23, the claim should read as “the therapeutic cell solution”.
The term “wound” in claim 23 is a relative term which renders the claim indefinite. The term “wound” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. What may be considered as a wound to one person may not be considered as such to another. Furthermore, it is noted “a subject” is not defined in the claim (not required to be a human).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, and 5-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frank et al, WO 2020/198611.
Frank discloses a device comprising a cryogenic vial (barcoded cryovial, see p. 17 I. 12 together with the definition of the abbreviation "BC" on p. 12 I. 28) comprising up to 12 x 106 ABCB5+ stem cells per ml (see p. 17 I. 13-14: upper end-point of the range 2 - 18 x 106 cells / BC, wherein each BC is filled with 1.5 ml cell suspension), see also Guidelines G-VI, 8. (iii), second sentence. A cryovial can be considered a "closed system" (in comparison to "open" cryopreservation carriers that allow for high cooling rates due to direct contact with LN2).
It is noted that claims 5-9 are not further limiting of claim 1. See Claim Interpretations and 112 rejections above.
As to claims 10-21, Frank discloses a method for preparing a unit dose of a therapeutic cell solution (see p. 27 I. 14-18), comprising
preparing a pooled population comprising ABCB5-positive cells (see "Pooling step to generate the Master Batch" on p. 17, and the corresponding box "Master Batch" in fig. 1 ),
concentrating the cells (p. 17 I. 2: "The solution is centrifuged ... ") and resuspending the concentrated cells (p. 17 I. 11 : "The cell pellets of the single batches are resuspended in CryoStor™ CS1 0") to produce a pooled sample having a cell concentration of up to 12 x 106 cells per ml (follows from p. 17 I. 13-14, where an upper end-point of the range 2 - 18 x 106 cells / BC is indicated, with each BC being filled with 1 .5 ml cell suspension).
Frank also discloses aliquoting a plurality of unit samples of cells from the pooled sample and transferring them to respective cryovials (p. 17 I. 13-21: "Each BC is filled with 1.5 ml cell suspension in CS10 ... The BC-tubes are frozen to -150 OC").
Note that claims 11 and 13-21 are negligible, not further limiting of the method in view of the “optionally clause” of claim 10. See rejections/remarks above.
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) 2, 4, and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frank et al., WO 2020/198611 as applied above, and further in view of Katz, US 11,766,459.
Frank does not specify that the vial comprises a fill tube.
The Applicant is advised that the Supreme Court recently clarified that a claim can be proved obvious merely by showing that the combination of known elements was obvious to try. In this regard, the Supreme Court explained that, “[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has a good reason to pursue the known options within his or her technical grasp.” An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of the case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. Furthermore, the simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR Int’l v. Teleflex Inc., 127 Sup. Ct. 1727, 1742, 82 USPQ2d 1385, 1397 (2007) (see MPEP § 2143).
Common sense, predictability, knowledge, and skill of one of ordinary skill in the art may suffice to establish obviousness.
Katz discloses in FIG. 1, a modified centrifuge tube 100, used in conjunction with various accessories known in the art, are comprised in a system or kit that allows for small physician practices as well as surgical centers to employ affordable methods for safe extraction of mesenchymal stem cells (MSCs) or SVF from adipose tissue of any patient or donor for use directly in treatment or for cryostorage (banking). (column 11, lines 22-29).
Tube 100 is provided with a cap 150 that is penetrated by several openings 115, 120, 121, and 122, and a separate fitting 110 mounted generally on a top portion of tube 100 near cap 150 (in fact, it should be appreciated by one having ordinary skill in the art that the various fittings, while all affixed to the upper portion of tube 100, may be arranged variously, with some, all, or none of the fittings passing through cap 150, and in fact cap 150 could optionally be omitted in favor of a tube 100 of unitary construction, which may be disposed of after use). Fitting 120 is penetrated by tube 129, which is fitted with a sterile fitting 125 (such as a luer lock), to allow various reagents or other fluids to be introduced via tube 129 without violating sterile conditions within tube 100. Typically, a sterile syringe is used to add fluids to tube 100 via tube 129. Tubes 130 and 131 penetrate through cap 150 at fittings 121 and 122 respectively, and are provided with sterile fittings 126 and 127, so that cells or other materials contained in a pellet at the bottom (the point of the inverted cone that makes up the lower portion of tube 100 after centrifuging (the creation of pellets of matter of relatively higher specific gravity during centrifuging is well known in the art). Fittings 126 and 127 may be of any type, such as a luer lock, known in the art and suitable for establishing a sterile connection between tubes 130, 131 and a syringe or other device capable of applying suction to remove cells from a pellet at the bottom of tube 100. Fitting 115 is penetrated by tube 116, which is fitted with a sterile fitting 117 at its end, and may be used to apply suction from the upper portion of tube 100 to establish a vacuum within tube 100 (for example, to facilitate rapid introduction of lipoaspirate into tube 100 through fitting 110). Fitting 110 is connected via a short tube or stub to fitting 111, which (like all the other fittings passing into tube 100) is suitable to maintaining sterile conditions within tube 100 at all times. Fitting 110 is generally used to inject lipoaspirate into tube 100 as an initial step of a process of extracting and potentially purifying or concentrating MSCs from the lipoaspirate into a pellet that can be withdrawn via either of tubes 130 and 131. In a preferred embodiment, two tubes 131, 131 are provided to ensure that pellet extraction will be possible even if one of the tubes becomes clogged. (column 12, lines 7-47; Figure 1).
It would have been obvious to and within the common sense, knowledge and skill of one ordinary skill in the art before the effective filing date of the invention to modify the vial to include tubes, openings (ports), and fittings to allow cells to be input into and removed from the vial and allow the vial the container to be connected to further structures (including containers) as taught by Katz.
As to claim 4, it would have been obvious to and within the common sense, knowledge and skill of one ordinary skill in the art before the effective filing date of the invention to recognize that the concentration of the stem cells may be adjusted within a solution as desired including the values of 13×10.sup.6+/−10% ABCB5+ stem cells per ml or 10.5×10.sup.6+/−10% cells/ml as such does not require any special skills beyond that of one of ordinary skill in the art.
As to claims 22-24, it is conventionally known in the art that tissue and stem cells may be employed for would healing. Such may be used in a variety of contexts, such as injected through a particular-size needle and/or for topical application for wound healing. (column 19, lines 54-56).
It would have been obvious to and within the common sense, knowledge and skill of one ordinary skill in the art before the effective filing date of the invention to remove the stem cell solution from the vial of Frank and apply such to a wound of subject in as many doses as desired and or required for healing of wound as taught by Katz.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. POPA MCKIVER; Mihaela Alina et al.; KUWAYAMA; Masashige et al.; Katz; Nathan et al.; NAKAMURA; Kentaro; Woods; Erik J. et al.; Liang; Ruei-Yue et al.; Katz; Nathan et al.; KITA; Shunbun et al.; DAVIES; John E. et al.; Delaney; Colleen; LOMBARDO DE LA CAMARA; Eleuterio et al.; UMEDA; Nobuyoshi et al.; PHAN; Toan Thang et al.; Sawa; Yoshiki et al.; Kerkis; Irina et al.; Ra; Jeong-Chan et al.; Woods; Erik John et al.; and Katz; Nathan disclose devices and methods related to stem cells.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN R GORDON whose telephone number is (571)272-1258. The examiner can normally be reached M-F, 8-5:30pm; off every other Friday..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN R GORDON/Primary Examiner, Art Unit 1798
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