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 1-26, of record 9/19/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/JP2023/007766 (filed 3/2/2023). Acknowledgement is made of the applicant’s claim for foreign priority to application 2022-046721 (filed 3/23/2022 in Japan).
Drawings
The drawings are objected to because view number must be preceded by the abbreviation “FIG.” and because each sheet must include a top margin of at least 2.5 cm. (1 inch), a left side margin of at least 2.5 cm. (1 inch), a right side margin of at least 1.5 cm. (5/8 inch), and a bottom margin of at least 1.0 cm. (3/8 inch). See 37 CFR 1.84(g) and (u). 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 use of the terms Ficol-Paque, FACSCanto II, and FACSCalibur, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
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 Objections
Claims 8-9, 17-18, and 22-23 are objected to because of the following informalities:
In claims 8-9, 17-18, and 22-23, the abbreviations “GLUT” and “GLUT1” should replace “glucose transporter” and “class-I glucose transporter”, as having been previously introduced in claims 3-4.
Appropriate correction is required.
Claim Interpretation
Claims 1 and 15 recite the limitation “CD18-positive cells in which CD18 is highly expressed”. The instant specification does not define “highly expressed”. The broadest reasonable interpretation of this limitation is considered to be greater than average expression of CD18 within individual cells or extensive expression of CD18 within a population of cells.
Claims 1 and 15 also recite “for treatment of ischemic disease”. Statements of purpose or intended use that do not set forth any distinct definition of the invention’s limitations are not considered to be limiting. See MPEP 2111.02(II).
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 1-26 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.
The term “highly expressed” in claims 1 and 15 is a relative term which renders the claims indefinite. The term “highly expressed” 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. Dependent claims 2-14 and 16-26 inherit the deficiency and are included in the rejection.
Regarding claims 4, 8-9, 18, and 22-23, the parenthetical “(GLUT1)” renders the claims indefinite because it is unclear whether the limitation within the parentheses is part of the claimed invention. See MPEP 2173.05(d).
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 15-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation.
Regarding claims 15-25: Claims 15-25 are directed to a cell preparation for treatment of ischemic disease comprising CD18+ cells in which CD18 is highly expressed, wherein at least 60% of the cells have a CD18-positive reaction; express a glucose transporter, a class-I glucose transporter, or GLUT1; express a connexin or connexin 43; express Jagged or Jagged1; and/or are stem cells or adult stem cells. The broadest reasonable interpretation of the claimed composition is considered to cover naturally occurring CD18+ cells. Based upon this interpretation, the claims are analyzed as follows:
Step 1: The claims are to a composition of matter, which is a statutory category of invention (Step 1: YES).
Step 2A, prong 1: CD18+ cells are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart.
The closest naturally occurring counterpart of CD18+ cells are naturally occurring CD18+ cells, such as CD34+ HSPCs (which read on “stem cells” and “adult stem cells”). CD34+ HSPCs express CD18 extensively (which reads on “highly expressed” and “the percentage of cells having a CD18-positive reaction is at least 60%”) (See Janowska-Wieczarek et al., fig. 2), along with GLUT1 (See Sarrazy et al., See fig. 2D and SIIB), connexin 43 (See Taniguchi Ishikawa et al., fig. 1E), and Jagged-1 (See Karanu et al., fig. 1C). There is no evidence that the cells as claimed differ from CD18+ cells in nature in terms of structural or functional characteristics. The claimed composition therefore does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Accordingly, the claims are directed to an exception (Step 2A, prong 1: YES).
Step 2A, prong 2: The claims are directed to a product and do not recite any structure that serves to integrate the composition into a practical application (Step 2A, prong 2: NO).
Step 2B: There are no additional elements required by the claims. The claims do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101.
Regarding claim 26: Claim 26 is directed to a cell preparation for treatment of ischemic disease comprising CD18+ cells in which CD18 is highly expressed and wherein the cell preparation improves or activates the enumerated physiological functions. The broadest reasonable interpretation of the claimed composition is considered to cover CD18+ cells. Based upon this interpretation, the claim is analyzed as follows:
Step 1: The claim is to a composition of matter, which is a statutory category of invention (Step 1: YES).
Step 2A, prong 1: CD18+ cells are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart.
The closest naturally occurring counterpart of CD18+ cells are naturally occurring CD18+ cells, such as CD34+ HSCs. CD34+ HSCs highly express CD18 (See Janowska-Wieczarek et al., fig. 2) and are able to improve brain function and circulation when administered following ischemic brain injury (See Abstract and page 331, col. 1, full ¶2 and col. 2, ¶2).
There is no evidence that the cells as claimed differ from CD18+ cells in nature in terms of structural or functional characteristics. The claimed composition therefore does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Accordingly, the claim is directed to an exception (Step 2A, prong 1: YES).
Step 2A, prong 2: The claim is directed to a product and does not recite any structure that serves to integrate the composition into a practical application (Step 2A, prong 2: NO).
Step 2B: There are no additional elements required by the claim. The claim does not qualify as eligible subject matter and is rejected under 35 U.S.C. 101.
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 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.
Claims 1, 3-15, and 17-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Taguchi et al. (Journal of Clinical Investigation, 2004), of record in IDS dated 9/19/2024, evidenced by Janowska-Wieczarek et al. (Blood, 2001), Sarrazy et al. (Circulation Research, 2016), Taniguchi Ishikawa et al. (Proceedings of the National Academy of Sciences, 2012), and Karanu et al. (Journal of Experimental Medicine, 2000).
Regarding claims 1, 3- 15, and 17-26: Taguchi et al. teach the administration of CD34+ human HSPCs (which read on “stem cells”, “adult stem cells”, “CD34-positive mononuclear cells”, and “hematopoietic stem cells”) for treating cerebral ischemia in a mouse stroke model (See Abstract). Treatment with HSPCs enhanced neovascularization of the ischemic zone and cerebral blood flow, as well as improved functional recovery (which read on “a brain function improver” and “a brain circulation improver”) (See page 331, col. 1, full ¶2 and col. 2, ¶2). Taguchi et al. do not expressly teach expression of CD18, a glucose transporter, a connexin, or Jagged in the cells.
Janowska-Wieczarek et al. teach that CD18 is “highly expressed” on CD34+ HPSCs (See fig. 2).
Sarrazy et al. teach that GLUT1 (which reads on “a glucose transporter” and “a class-1 glucose transporter”) is expressed on the surface of CD34+ HPSCs from control (Mx1-Cre) and wt mice (See fig. 2D and SIIB).
Karanu et al. teach Jagged-1 (which reads on “Jagged”) as being expressed by CD34+Lin- cord blood mononuclear cells (equivalent to HSPCs) (See fig. 1C).
Taniguchi Ishikawa et al. teach that CD34+ HSPCs express connexin 43 (which reads on “a connexin”) (See fig. 1E).
The cells and method of Taguchi et al. therefore anticipate the claimed invention.
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 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over Taguchi et al. (Journal of Clinical Investigation, 2004), of record, evidenced by Janowska-Wieczarek et al. (Blood, 2001), Sarrazy et al. (Circulation Research, 2016), Taniguchi Ishikawa et al. (Proceedings of the National Academy of Sciences, 2012), and Karanu et al. (Journal of Experimental Medicine, 2000), in view of Overton (Cytometry, 1988).
The teachings of Taguchi et al., Janowska-Wieczarek et al., Sarrazy et al., Taniguchi Ishikawa et al., and Karanu et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 2 and 16: Following the discussion of claims 1, 3-15, and 17-26, Taguchi et al. teaches a method for treating ischemic brain injury by administration of CD34+ HSPCs. The teachings of Janowska-Wieczarek et al. are cited as evidence that the cells inherently express high levels of CD18, shown by flow cytometry (which reads on “a CD18-positive reaction”) (See fig. 2). However, Janowska-Wieczarek et al. do not expressly teach the percentage of cells exhibiting CD18 staining.
Overton teaches that histogram subtraction can be used to determine the percentage of positive cells detected by flow cytometry (See Abstract). No overlap in channels is seen with 100% positive cells, and the overlap with the control channel increases with decreased labeling (See fig. 1).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention that, based on the teachings of Overton, the percentage of CD18+ cells in the CD34+ HSPC population taught by Janowska-Wieczarek et al. could be estimated as being substantially higher than 60%. The small amount of overlap between the CD18-labeled and unlabeled density curves suggest that CD18+ cells comprise approximately 90% or more of the total CD34+ HSPC population (See fig. 2B) and renders obvious the instant claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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