DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 18246471, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19 are pending.
Priority
The filing receipt, mailed 5/13/2024, states that applicant claims Domestic Priority benefit for this application as a 371 of PCT/EP2021/076259, filed 09/23/2021 and Foreign priority benefit of Application: FRANCE FR2009679, filed 09/23/2020. No certified English translation of the certified foreign priority document appears to be of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/23/2023, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 13, 14 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.
Dependent Claim 13 recites the limitation "as active substance" in line two. There is insufficient antecedent basis for this limitation in the claim. Also, clarity would be supported by an article in front of the claim term “active.”
Claims 14 lacks a verb and is unclear.
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 9-13 and 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) products of nature. This judicial exception is not integrated into a practical application because the claimed population of cultured red blood cells is a product by process. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed cultured red blood cells do not appear to be markedly different from their natural counterparts.
The instant Specification does not appear to describe how the claimed cultured red blood cells are markedly different from their natural counterparts.
The Specification at p. 2, lines 5-8, contemplates industrial production of cultured red blood cells that have a “functionality similar to native red blood cells.” The Specification at pp. 18, lines 10-13, states “[t]he cultured red blood cells according to the invention have features similar to those of native reticulocytes. As is well known to the skilled person, reticulocytes are derived from erythroblasts by enucleation. This is illustrated by the following Example. Some cultured red blood cells according to the invention may have features similar to those of native red blood cells.”
The Specification in the Example at pp. 23-26, compared the red blood cells obtained by method of the invention to native red blood cells, particularly placental blood reticulocytes, (see Table 1 at p. 24). According to this comparison, the Specification, at p. 25, lines 22-25, state: “The method according to the invention produces cultured red blood cells with features close to native reticulocytes. In addition, the low variability of the measurements performed indicates that the risk of deviating from the features of native reticulocytes is low”. The Specification states:
The only significant difference with the native reticulocytes studied is the reversed content of fetal and adult Hb. This difference is justified by the fact that cultured red blood cells are now produced from adult stem cells (and therefore contain mostly adult hemoglobin), while control reticulocytes are derived from placental blood (and therefore contain mostly fetal hemoglobin}.
Specification at p. 25, lines 10-14.
Thus, because the claimed cultured red blood cells do not appear to be markedly different from their natural counterparts, Claims 9-13 and 19 claim a natural product without significantly more, and so are rejected under 35 USC 101 as a judicial exception.
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.
1. Claim(s) 1-6, 8, 9, 13, 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lipsitz, WO 2020/243006, (of record, IDS), Goldstein, US 6,455,306, (of record, IDS), Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS), and Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS).
Lipsitz, WO 2020/243006, (of record, IDS), throughout the publication and abstract and e.g., p. 1, line 10-p. 3, line 4; p. 11, line 27-p. 12, line 5, discloses a method for producing enucleated erythroid cells, characterized by the culture of erythroid progenitor cells carried out in a perfusion bioreactor, making it possible to obtain a density of up to 10 million cells/ml. The culturing of cells in a bioreactor in batch mode or fed-batch mode before the perfusion culture is also described (page 2, lines 5-15). Example 1 shows that the perfusion culture makes it possible to obtain a percentage of enucleated cells 70-80% higher than the fed-batch culture. The cell density is also higher, being able to reach a maximum of 14 million cells/ml, as opposed to 2 million cells/ml with a fed-batch culture. Lipsitz at p. 1, lines 10-14, teach that engineered enucleated erythroid cells are in development as therapeutic agents for patients in need thereof. Lipsitz, at p. 35, line 26-p. 36, line 7, provides a description of the term “erythroid progenitor cells”, to include that it can be a cord blood stem cell; at, e.g., manual removal of culture medium, for example by sterile pipetting.
Lipsitz does not appear to teach washing the cells to produce a population of cultured red blood cells.
Goldstein, US 6,455,306, (of record, IDS), discloses the production of human erythrocytes from adult HSC cells from bone marrow or peripheral blood (column 6), using a method including three consecutive bioreactors, a first for amplifying the HSCs, the second for differentiation thereof and the third for maturation into erythrocytes (reference claims 1-14). The bioreactors are used in perfusion mode (column 13, entire first paragraph). The mature erythrocytes are recovered when the population contains 90% enucleated cells, washed at least 3 times and sterilized so as to destroy any possible contaminating nucleated cell (examples, columns 13-15). Goldstein, at col. 11, line 58-col. 12, line 19teach transferring harvested erythrocytes to a cell separator and washed to remove residual nutrient media, proteins and the like in preparation for producing a clinically transfusable composition.
Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS) describes the production of human erythrocytes in a three-dimensional hollow fiber bioreactor (3DHFR) from fetal mononucleated cells from umbilical cord blood. The mononucleated cells are cultivated in the 3DHFR bioreactor for 1 hour without perfusion, followed by a culture with perfusion for 28 days (page 25, §2.5). The cells are collected, filtered and analyzed on days 14 and 28. A cell density of > 2000 million cells/ml is obtained, including the enucleated red blood cells (pages 33-34, §3.3 and figure 5).
Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS), describes the in vitro generation of erythrocytes from CD34+ adult HSCs from peripheral blood. The expansion and differentiation by sequential addition of SCF, IL-3 and EPO made it possible to obtain a population containing 81% enucleated cells having the properties of native erythrocytes and reticulocytes (pages 5073-5074, "In vitro generation of functional RBCs..."). These cultured erythrocytes (CRBCs) contain 88% HbA and 10% Hbf, respectively. A million CD34+ HSCs made it possible to produce, in 18 days, 37,000 million total cells, the erythrocytes of which were purified before being injected into a human recipient (page 5075, first paragraph and page 5077, figure 5).
It would have been prima facie obvious before the effective filing date of the application for one of ordinary skill in the art to have washed the erythrocytes to produce a population of cultured red blood cells, as taught by Goldstein, in the method for producing cultured red blood cells, as taught by of Lipsitz, Allenby and Giarratana.
One of ordinary skill in the art would have been motivated to wash the cultured red blood cells to produce a more refined product for red blood cell transfusion in the treatment of patients.
2. Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lipsitz, WO 2020/243006, (of record, IDS), Goldstein, US 6,455,306, (of record, IDS), Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS), and Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS). as applied to claims 1-6, 8, 9, 13, 19 above, and further in view of Zamzami, US 2021/0001333.
The teachings of Lipsitz, WO 2020/243006, (of record, IDS), Goldstein, US 6,455,306, (of record, IDS), Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS), and Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS) are relied upon, as set forth above.
Lipsitz, WO 2020/243006, (of record, IDS), Goldstein, US 6,455,306, (of record, IDS), Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS), and Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS), do not teach or suggest dead-end filtration of cells.
Zamzami, US 2021/0001333, at para {0093], [0103], teaches dead-end filtration of red blood cells as a system to retain red blood cells.
It would have been prima facie obvious before the effective filing date of the application for one of ordinary skill in the art to have used the dead-end filtration of red blood cells, as taught by Zamzami, with the method of producing cultured red blood cells, as taught by Lipsitz, WO 2020/243006, (of record, IDS), Goldstein, US 6,455,306, (of record, IDS), Allenby, August 2018, Biomaterials, vol. 188, pages 24-37, (of record, IDS), and Giarratana, 2011, Blood, Nov 2011, Vol. 118, No. 19, pp. 5071-5079, (of record, IDS).
One of ordinary skill in the art would have been motivated to employ dead-end filtration in the method of producing cultured red blood cells, because Zamzani teaches that dead-end filtration can be preferred for isolation of red blood, depending on the embodiment of the system.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631