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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found
in a prior Office action.
This Action is in response to the papers filed on May 15, 2026. Pursuant to the amendment filed on May 15, 2026, claims 1-20 are currently pending of which claims 1 and 8 have been amended. No claims have been cancelled and no claims have been added.
Therefore, claims 1-20 are currently under examination to which the following grounds of rejection are applicable.
Response to Arguments
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments:
Claim Rejections - 35 USC § 102
In view of Applicants’ Amendments to the claims filed on May 15, 2026, of which claims 1 and 8 have been amended, the rejection to claims 1-2 rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rehak et al. (Clinical chemistry 34.10 (1988): 2111-2114), have been withdrawn.
Claim Rejections - 35 USC § 103
In view of Applicants’ Amendments to the claims filed on May 15, 2026, of which claims 1 and 8 have been amended, the rejection to claims 1, 3-20 rejected under 35 U.S.C. 103 as being unpatentable over Rehak et al. (Clinical chemistry 34.10 (1988): 2111-2114) as applied to claims 1-2, and further in view of Honmou et al. (US 9,700,582 B2), have been withdrawn. The withdrawn rejections is in view of the amended claims that have narrowed the scope of the claims to recite the time duration limitation to 30 hours up to 48 hours. The Rehak reference only teaches up to 24 hours of the whole blood standing at the claimed temperature.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to any argument pertaining to a new or maintained rejection can be found below.
New Grounds of Rejection
Claim Rejections - 35 USC § 102
Claims 1-2 are newly rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ono et al. (Clinical chemistry 27.1 (1981): 35-38.; hereinafter ‘Ono’). This is a new rejection necessitated by Applicants' amendments to the claims in the response filed on May 15, 2026.
Claim 1 is directed to a method for producing serum for culturing mammalian cells, the method comprising: maintaining blood collected from a first mammal at a temperature between 15 ̊C and 25 ̊C for more than 30 hours and up to 48 hours and preparing serum from the blood.
Ono teaches serum derived from whole blood of healthy women volunteers stood at 23°C for 48 hours in relation to samples over a range of temperatures, e.g. 4 and 30°C, and time durations, e.g. 0, 2, 4, 6, 8, 24, or 48 h, prior to separation (abstract; Fig. 1-4; p 1, col 1, par 3-4).
Secondly, Ono does not teach the method in view of the claimed intended use for culturing mammalian cells; however, it is clear based on the structure of the claim that using the serum for culturing is not being actively claimed. MPEP 2111.02 states, “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim.” In the instant case, there are no clear manipulative differences nor structural differences between the cellular elements therein used or obtained, i.e. cells, serums, blood. In particular, there are no other limitations present that differentiates the serum of Ono from the instant application’s, as such Ono’s serum is expected to function similarly to the instant application’s in culturing mammalian cells.
Regarding claim 2, dependent on claim 1, Ono teaches wherein the first mammal is a human (“The subjects were healthy women volunteers,” (p 1, col 1, par 3-4)).
Claim Rejections - 35 USC § 103
Claims 1-20 are newly rejected under 35 U.S.C. 103 as being unpatentable over Ono et al. (Clinical chemistry 27.1 (1981): 35-38.; hereinafter ‘Ono’) as applied to claim 1-2 above, and further in view of Rehak et al. (Clinical chemistry 34.10 (1988): 2111-2114; hereinafter ‘Rehak’) and Honmou et al. (US 9,700,582 B2; hereinafter ‘Honmou’). This is a new rejection necessitated by Applicants' amendments to the claims in the response filed on May 15, 2026.
The teachings of Ono are discussed supra, wherein Ono teaches the claimed serum recited in claims 1-2.
Similarly to Ono, yet at a slightly shorter duration, Rehak teaches the collection of whole blood into serum separation tubes, wherein the samples were stored 24 h at different temperatures, a range that includes 15, 22, and 25 °C. After storage, the samples were centrifuged to obtain the serum from the clots, and serum analytes were measured (p 2112, col 2). Rehak describes that most of the serum analytes measured were unaffected by an extended storage time of the serum with the cell clot at temperatures ranging from 3 to 38°C, and the variation observed was within the expected precision seen with day-to-day results. Across the 29 analytes measured, six analytes, i.e. creatinine, glucose, inorganic phosphorus, potassium, and both alanine and aspartate transferases, had significant differences that were storage temperature dependent (p 2112, col 2; p 2114, col 2). However, these changes were only significant outside the range of 15-25°C for which the instant claims are directed. Lastly, Rehak describes the standard practice of separating serum from whole blood within two hours of collection in order to maintain clinically useful and reliable test results, yet the instant application is directed to the method of obtaining serum for cell culturing, particularly mammalian cell culture.
Ono and Rehak do not teach comprising examining an aliquot of the blood or prepared serum for either one or both of a tumor marker and an infectious factor.
Honmou teaches examining prepared serum for either one or both of a tumor marker and an infectious factor (“Preferably the allogeneic serum has been determined as being negative for a serum tumor marker and/or an infectious factors,” (abstract)).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the known technique of screening the serum for a tumor marker and/or an infectious factor in order to determine if the serum can be used for culturing as this technique has been described by Honmou for allogeneic serum, and therefore, it would be obvious to apply this known technique with the serum of Ono or Rehak that have obtained from whole blood kept at room temperature for at least 24 hours, more specifically up to 48 hours as taught by Ono, to then be used in mammalian cell culturing as there is a predictable level of success it would behave similarly to the serum taught by Honmou.
Regarding claims 4 and 5, both dependent on claim 1, Ono teaches a method for producing serum as outline in the rejections for claims 1-2 above, and moreover teaches the serum is derived from humans as the samples are obtained from “healthy women volunteers.” (p 1, col 1, par 3-4).
Ono does not teach the serum is used for cell culturing, and therefore does not teach wherein the mammalian cells are cells derived from a second mammal of the same species as the first mammal as this relates to cell culturing. Furthermore, Ono does not teach wherein the mammalian cells are cells derived from the same mammal as the first mammal.
Honmou teaches “a method for growing cells in a sample collected from a living subject by culturing the cells in a medium, the method characterized by comprising culturing the cells… in a medium containing allogeneic serum. In this context, it is preferred that the allogeneic serum should have been determined to be negative for a serum tumor marker and/or an infectious factors.” (col 9, ln 36-43). Furthermore, Honmou describes “the cells to be cultured are human cells” and in relation to the serum, “using foreign animal serum (e.g., FBS) or serum of another individual of the same species as the human (allologous serum).” The teachings also extend to using autologous serum wherein the cells and serum are from the same subject (col 10, ln 64-67). Honmou states when autoserum (autologous serum) is difficult to obtain using serum from other humans can be employed wherein the high cell growth rate can still be obtained (col 15, ln 14). Moreover, Honmou describes the advantage of using autologous cells in view of ethical problems, infection risk, and the need to use immunosuppressive agents with non-autologous cells (cell rejection) (col 14, ln 16-29),
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use either autologous or allogeneic cells in relation to the serum with a reasonable expectation of success based on this being well-known at the time of filing of the instant application. Moreover, Honmou describes the advantage of using autologous cells in view of ethical problems, infection risk, and the need to use immunosuppressive agents with non-autologous cells (cell rejection) (col 14, ln 16-29), and therefore there is clear motivation to use both the serum and cells that originate from the same subject for culturing purposes in view of downstream applications. Lastly, there is a reasonable expectation that the serum produced by Ono would function in the culturing of mammalian cells that originate from the same individual or rather species based on this being taught explicitly by Honmou as seen with autologous and allogeneic serum.
Regarding claims 6 and 7, both dependent on claim 1, Ono does not teach the serum is used for cell culturing, and therefore does not teach wherein the mammalian cells are stem cells, and wherein the mammalian cells are bone marrow-derived mesenchymal stem cells (BM-MSC).
Honmou teaches the cells that are used with serum for cell culturing are stem cells in particular bone marrow-derived mesenchymal stem cells as seen in Example 1 wherein bone marrow fluid was collected from a brain disease patient and on day 4 mesenchymal stem cells were obtained then cultured. Additionally, Honmou describes advantages of BM-MSC, “The use of bone marrow-derived mesenchymal stem cells for repair of a tissue of the nervous system has, for example, the following advantages: 1) the cells can be expected to produce significant effects, 2) they carry low risk of side effects, 3) sufficient donor cells can be expected to be supplied, 4) they achieve noninvasive treatment and autotransplantation; thus 5) such cell therapy carries low infection risk, 6) it is in no danger of immune rejection, 7) it produces no ethical problem, 8) it is easily socially acceptable, and 9) it is easily established widely as general medical care. Furthermore, the bone marrow transplantation therapy is treatment already used in clinical practice and has also been confirmed to be safe. Moreover, the bone marrow-derived stem cells, which have high migration properties, can arrive at the intended injured tissue not only by local transplantation but also by intravenous administration to exert their therapeutic effects thereon.”(col 17, ln 22-38).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected bone marrow-derived mesenchymal stem cells (BM-MSC) as the type of cell to be cultured with the serum produced by Ono based on the many advantages outlined by Honmou for downstream applications. Moreover, there is a reasonable expectation that by culturing BM-MSC with the serum of Ono, the cells would be able to proliferate based on Honmou teaching this outcome with autoserum.
Claim 8 is directed to a method for producing a medicament comprising cultured mammalian cells, the method comprising culturing mammalian cells in a culture medium, wherein the culture medium contains serum for culturing the mammalian cells, and the serum is prepared from blood collected from a first mammal by maintaining the blood at a temperature between 15 °C and 25 °C for more than 30 hours and up to 48 hours.
Regarding claims 8 and 9, Ono teaches a method for producing serum as outline in the claim 1 rejection above, and moreover teaches the serum is derived from “healthy women volunteers.” (p 1, col 1, par 3-4).
Ono does not teach the serum is used for cell culturing, and therefore does not teach the entirety of claim 8, in particular the medicament comprising cultured mammalian cells and where mammalian cells are human.
Honmou teaches using the serum and human mesenchymal stem cells from a patient to produce a therapeutic drug that can be delivered back to the patient in which the outcome revealed significant improvement effects on cerebral infarction (Example 5). Additionally, Honmou teaches a pharmaceutical preparation for tissue repair/regeneration comprising the cells grown by the method of using either autologous or allogeneic serum for cell culturing (col 16, ln 1-5; col 9, ln 36-43).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared a medicament comprising cultured human mammalian cells with a reasonable expectation of success using the method of preparing a serum as taught by Ono and Rehak based on Honmou teaching the culturing of MSCs with autoserum for downstream therapeutic applications wherein outcomes were improved. Secondly, the step of using the cultured MSCs as part of a medicament is well-known in the field tissue regeneration and repair as Honmou describes (col 15).
Regarding claim 10, dependent on claim 8, Honmou teaches the method further comprising examining an aliquot of the blood or prepared serum for either one or both of a tumor marker and an infectious factor as seen in the claim 3 rejection above (“Preferably the allogeneic serum has been determined as being negative for a serum tumor marker and/or an infectious factors,” (abstract)).
Regarding claim 11, dependent on claim 8, Honmou teaches wherein the culture medium contains the serum at 1 to 20% per medium volume (col 4, ln 49-50).
Regarding claim 12, dependent on claim 8, Honmou teaches wherein the culture medium contains anticoagulant at less than 0.02 U/ml per volume of the medium (col 10, ln 27-32).
Regarding claims 13-16, the rejections to claim 4-7, respectively, are applied herein, and can be found above in their entirety.
Regarding claim 17, dependent on claim 8, the claim is directed to a third mammal that is different than the mammal from which the cells and serum originate, in particular the third mammal is the subject to be treated with the medicament. Ono teaches a method for producing serum as outline in the claim 1 rejection above, and moreover teaches the serum is derived from humans (p 1, col 1, par 3-4).
Ono does not teach the third mammal or rather the patient is different that provider of the serum.
Honmou teaches that the donor cells are preferably from the subject to be treated but that it is not required as seen in using allogeneic or allologous cells (“Examples of donor cells used in tissue repair and regeneration include autologous or allologous tissue stem cells or somatic stem cells, or embryonic stem cells.” (col, ln 18-20; col 16, ln 49-52)). Honmou teaches many advantages of using autologous cells, but acknowledges that “Cells derived from other humans or other animals may be used when the autotransplantation therapy is difficult.” (col 16, ln49- col 17-38).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention wherein the subject is different than the donor of either the serum or cells included in the medicament based on non-autologous cell therapies being well-known in the field. In particular, Honmou primarily teaches using autologous cells for pharmaceutical preparations to prevent complications related to immune rejections or other side effects, but acknowledges non-autologous cells can be used as an alternative. Therefore, it would have been obvious for the subject to be different than the donor of the cells and/or serum based on this approach being clearly taught.
Regarding claim 18, dependent on claim 8, Honmou teaches wherein the mammalian cells are collected in a condition where anticoagulant is added to a biological sample collected from the second mammal at less than 0.2 U/ml per volume of the sample so that the mammalian cells do not substantially contact with the anticoagulant (“The cells are kept from substantial contact with the anticoagulant.” (col 10, ln 15-19); “In a preferable aspect of the present invention, the amount of the anticoagulant added to the sample collected from a living subject (i.e., previously placed in a blood collection tube for containing the collected sample) is less than … 0.2 U/mL, with respect to the volume of the sample.” (col 10, ln 27-31)).
Regarding claim 19, dependent on claim 8, Honmou teaches wherein the anticoagulant is heparin, heparin derivative, or salt thereof (col 4, ln 37-39).
Regarding claim 20, dependent on claim 8, Honmou teaches wherein the medicament is for treating spinal cord injury, stroke, dementia, or spinal cord infarction (col 16, ln 22-32).
Response to Applicants' Arguments as they apply to rejection of claims 1-20 under 35 USC § 103
Starting on page 6 of the remarks filed on May 16, 2026, Applicants essentially argue the following:
In relation to claims 1 and 8, Applicants' state “Rehak fails to disclose each and every feature of pending claim 1, on which claims 3-7 depend. Honmou fails to remedy the deficiencies in Rehak because it was cited as allegedly disclosing features found specifically in claims 3-7. With respect to claim 8, on which claims 9-20 depend, Applicant submits that the combination of Rehak and Honmou fails to render obvious any of these rejected claims. As explained above, Rehak fails to disclose "maintaining the blood at a temperature between 15 °C and 25 °C for more than 30 hours and up to 48 hours" recited in claim 1.”
In response to the argument it has been fully considered but is not persuasive due to the following reasons:
Regarding the first presented argument, the New Ground of Rejections recited above no longer employs Rehak in view of Honmou in teaching the step of obtaining serum as described in claims 1 and 8, but now employ the Ono reference in combination with Rehak and Honmou to teach limitations pertaining to using the obtained serum for cell culturing wherein Ono clearly teaches the new period of time for which the blood collected is maintained of which serum is prepared. Therefore, arguments pertaining to only Rehak in view of Honmou are considered moot as these rejections have been withdrawn.
Conclusion
Claims 1-20 are rejected. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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