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 .
Priority
This application was filed on the 24th of Sept. 2024, and is a 371 application of PCT/KR2023/004918 filed on 4th of Dec. 2023, which claims benefit to the foreign application KR 10-2022-0045251 filed on 12th of April 2023.
Claim Status
Applicant filed on the 24th of Sept. 2024, amended claims 1-3, cancelled claim 9, and filed new claims 15-20.
Currently, claims 1-8, and 10-20 are pending in this application and are under consideration in this office action.
Claim Objections
Claim 1 and 19 are objected to because of the following informalities: grammar/awkward.
Claim 1 recites “a method for nucleated cell death induction in incubating blood cells” (lines 1-2). It is suggested that the claim removes the term “in” because the phrase “induction in” suggests that the incubated blood cells are incubated with something that is not recited in the claim.
Claim 19 recites “A method for producing red blood cell,” and appears to be missing an indefinite article (e.g. “a red blood cell”). For compact prosecution the claim will be interpreted as referring to any red blood cell.
Specification
The use of the terms “Invitrogen” (see e.g. para. 50), “BD Bioscience” (para. 49), and “Stemspan” (para. 44), 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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 24th of Sept. 2024, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Notably, the disclosure statements filed lists a “Search Reports”. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
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 1-5, 10-14, and 17-18 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 1, the claim recites “a method for nucleated cell death induction in enucleated incubating blood cells, comprising: incubating hematopoietic stem cells or progenitor cells into enucleated blood cells; and killing nucleated cells by a low temperature treatment of the incubating blood cells,” (lines 1-6). However, it is unclear if the limitation of "killing nucleated cell" in line 5 is referring to hematopoietic stem cells or progenitor cells. Therefore, the claim is indefinite because the claims uses a generic term to refer back to the specific nucleated cells, which are not defined in the claims. For compact prosecution, the phrase “killing nucleated cell” will be interpreted as referring to the incubated hematopoietic stem cells or progenitor cells as referred to in claim 6 (i.e. “The method for nucleated cell death induction of claim 1, wherein the nucleated cells are erythroid progenitor cells or platelet progenitor cells that overexpress proliferation-related genes). Appropriate correction is required.
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 1-6, 10-11, 15, and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baek, Eun-jeong (KR20130015481A, published 2013, hereinafter as “Baek”, cited IDS 9/24/2024).
Regarding claim 1, 10 and 19-20, Baek discloses a method for nucleated cell death induction in incubating blood cells (see e.g. abstract). Baek discloses incubating hematopoietic stem cells or progenitor cells into enucleated blood cells (see e.g. abstract, pg 2, 5, claims 1-8, Examples 1-3). Further, Baek discloses incubating the red blood cells by a low temperature treatment (i.e. refrigerated at 4°C)(see e.g. abstract, pg 2, 5, claims 1-8, Examples 1-3), corresponding to the claim limitation of wherein the low temperature treatment is performed at 0°C or higher and 15°C or lower.
Regarding the claim limitation of killing nucleated cells by a low temperature treatment, while Baek does not explicitly state killing nucleated cells by a low temperature treatment, however, it is considered an inherent property of the claimed method.
Regarding the issue of inherency, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims." In the instant case, the claims are drawn to an invention employing the same process steps, but the product(s) is(are) alleged to be different. Applicant is required to recite the missing steps to form the alleged different product(s) in view of the above-cited decision. If this is the case, Applicant is required to recite the missing steps. In the instant case, as discussed above, Baek discloses incubating the red blood cells by a low temperature treatment (i.e. refrigerated at 4°C). Therefore, Baek inherently discloses killing nucleated cells by a low temperature treatment.
Regarding claim 2, Baek discloses wherein the hematopoietic stem cells or progenitor cells are isolated from bone marrow, umbilical cord blood, or peripheral blood (see e.g. abstract, pg 2, 4-5, claims 1-8, Examples 1-3).
Regarding claim 3, Baek discloses wherein the progenitor cells comprise erythroid progenitor cells (see e.g. abstract, pg 2, 4-5, claims 1-8, Examples 1-3).
Regarding claim 4, Baek discloses wherein the enucleated blood cells comprise enucleated erythrocytes (see e.g. abstract, pg 2, 4-5, claims 1-8, Examples 1-3).
Regarding claim 5, Baek discloses wherein the enucleated erythrocytes are selected from the group consisting of reticulocytes and erythrocytes (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Regarding claim 6, Baek discloses wherein the nucleated cells are erythroid progenitor cells overexpress proliferation-related genes (i.e. GATA1)(see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Regarding claim 11, Baek discloses passing the incubating blood cells through a leukocyte-reducing filter (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Regarding claim 15, Baek discloses wherein the hematopoietic stem cells or progenitor cells are derived from stem cells, erythroid progenitor cell lines, embryonic stem cells, or iPS cells (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Regarding claim 19, as stated supra, Baek discloses differentiating erythroid progenitor cell lines into mature erythrocyte; passing the differentiated mature erythrocyte through a leukocyte-reducing filter to gather red blood cells; and treating the filtered red blood cell in a low temperature refrigeration, wherein the low temperature is at 0°C or higher and 15°C or lower (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Regarding claim 20, as stated supra, Baek discloses wherein the filtered red blood cell includes nucleated cells; and wherein the treating in a low temperature refrigeration induces death of the nucleated cells in the filtered red blood cell (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
In conclusion, the prior art of Baek anticipates the claims because it inherently discloses all the required limitations.
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.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Baek, Eun-jeong (KR20130015481A, published 2013, hereinafter as “Baek”, cited IDS 9/24/2024), as applied to claims 1-5, 10-11, 15-16, and 19-20 above, and further in view of Trakarnsanga, Kongtana, et al. (Nature communications 8.1: 14750, published 2017, hereinafter as “Trakarnsanga”).
The teachings of Baek apply here as indicated above.
Regarding claim 6-7, Baek does not explicitly state wherein the nucleated erythroid progenitor cell lines overexpress proliferation-related genes, wherein the proliferation-related gene is HPV16 E6/E7.
However, the prior art of Trakarnsanga discloses wherein the nucleated cells are erythroid progenitor cells or platelet progenitor cells that overexpress proliferation-related genes, wherein the proliferation-related gene is HPV16 E6/E7 (see e.g. whole document).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods, as taught by Baek, and incorporate the proliferation-related gene is HPV16 E6/E7, as taught by Trakarnsanga, with a reasonable expectation of success because one of ordinary skill in the art would want to detect any remaining nucleated cells that might be obtained in the final product, which would be required for erythroid cultures from all stem cell sources (as taught by Trakarnsanga, see e.g. page 5).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 8 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Baek, Eun-jeong (KR20130015481A, published 2013, hereinafter as “Baek”, cited IDS 9/24/2024), as applied to claims 1-5, 10-11, 15-16, and 19-20 above, and further in view of Baek et al., (KR20110094470A, published 2011, hereinafter “Baek et al., (2011)”; cited IDS 9/24/2024).
The teachings of Baek apply here as indicated above.
Regarding claim 8 and 17, Baek discloses incubating the red blood cells by a low temperature treatment (i.e. refrigerated at 4°C) for up to one month (i.e. 30 days)(see e.g. abstract, pg 2, 5, claims 1-8, Examples 1-3).
Baek does not explicitly state wherein the low temperature treatment is performed by refrigeration for 3 to 10 days.
However, the prior art of Baek et al., (2011), discloses that on the 13th day of culture the cells were transferred to low temperature conditions until day 19 or 21 (i.e. about 6-8 days), which reads on the claimed 3-10 days (see e.g. page 1-3, fig. 1-6).
Further, the following is noted from the MPEP: MPEP 2144.05: “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” In regards to overlapping ranges, MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, continuing in regards to ranges are close, “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
In the instant case, neither the specification nor Applicant have provided evidence of that the claimed range of days for low temperature treatment is critical, thus the teaching of about 6-9 days as taught by Baek et al., (2011), renders the claimed time period as obvious.
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods, as taught of Baek, to incorporate the low temperature treatment of 3 to 10 days, as taught by Baek et al., (2011), with a reasonable expectation of success because one of ordinary skill in the art would know that the cell morphology was well maintained at low temperature and optimal number of enucleated cells would be obtained (as taught by Baek et al., (2011), see e.g. page 1-4).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 12-13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Baek, Eun-jeong (KR20130015481A, published 2013, hereinafter as “Baek”, cited IDS 9/24/2024), as applied to claims 1-5, 10-11, 15-16, and 19-20 above, and further in view of Spadafora, Domenico, et al. ("Methods for efficient elimination of mitochondrial DNA from cultured cells." PLoS One 11.5: e0154684, published 2016), and Chen, Szu-Jung, et al. (Oncotarget 6.10: 8007, published 2015), and Hatta et al., (US9290737B2, published 2016).
The teachings of Baek apply here as indicated above.
Regarding claim 12-13, and 18, as stated supra, Baek discloses passing the incubating blood cells through a leukocyte-reducing filter (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Baek does not explicitly state irradiating the incubating blood cells; and treating nuclease.
However, the prior art of Chen and Spadafora discloses irradiating the incubating blood cells; and treating nuclease (see e.g. abstracts, respectively).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods, as taught by Baek, and incorporate irradiating and treating nuclease of the incubating blood cells, as taught by Chen and Spadafora, with a reasonable expectation of success because one of ordinary skill in the art would know that irradiating incubated blood cells and treating with nuclease (as taught by Chen and Spadafora, see e.g. abstracts, respectively) were well-known enucleated method techniques for enucleating stem cells.
Regarding claim 14, as stated supra, Baek discloses treating nucleated cells in low temperature (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3). Baek discloses obtaining a high purity of red blood cells (See e.g. fig. 2) and increase in denuclearization rate (see e.g. fig. 6).
Baek does not explicitly state wherein the death rate of nucleated cells in the low temperature treated cells is 97% or higher.
However, the prior art of Chen discloses where greater than 95% of the cells are denucleated (i.e. dead) after treatment (see e.g. page 8009, fig. 1-2)
Furthermore, MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.” The “wherein” clause(s) following the active steps in describe(s) qualities of the resulting treated cell culture but does not require active steps or define structural limitations.
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the nucleated cells, as taught by Baek, in the low temperature treated cells is 97% or higher, as taught by Chen, with a reasonable expectation of success because one of ordinary skill in the art would want to obtain a high purity of red blood cells and increase in denuclearization rate (as taught by Chen and Baek, see e.g. figs. 2 and 6, respectively).
Regarding claim 16, Baek discloses wherein the erythroid progenitor cells are selected from the group consisting of proerythroblasts, basophilic erythroblasts, polychromatic erythroblasts, and orthochromatic erythroblasts (see e.g. abstract, pg 2, 4-5, 8, fig. 2, claims 1-8, Examples 1-3).
Baek does not explicitly discloses wherein the erythroid progenitor cells are burst forming unit erythroid (BFU-E) or colony forming unit erythroid (CFU-E).
However, the prior art of Hatta discloses erythroid progenitor cells are burst forming unit erythroid (BFU-E) or colony forming unit erythroid (CFU-E).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the method, as taught of Baek, to incorporate the erythroid progenitor cells are burst forming unit erythroid (BFU-E) or colony forming unit erythroid (CFU-E), as taught by Hatta, with a reasonable expectation of success because one of ordinary skill in the art would want to ensure that the erythroid precursor cells can differentiate into a blood cell in only one direction (i.e. an erythroid cell lineage), which can be identified by the burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) erythroid progenitor cells (as taught by Hatta, see erythroid precursor cell section).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights