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 .
Prosecution has been reopened to add Ramanov (EP 2298328) to the first obviousness rejection in view of the Pre-appeal conference mailed 9-11-25.
Claims 1-23, 26-49 have been canceled. Claims 24 and 25 remain pending.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim objection
Claim 24 as amended never requires “administering [ ] 2x107 cells/kg of allogenic human cord blood mononuclear cells” to a human because the phrase “to a human” has been deleted.
The phrase “cerebral palsy” in line 4 of claim 24 can be abbreviated.
Claim 24 can be written more clearly as ---A method of treating cerebral palsy (CP), the method comprising:
systemically or intrathecally administering at least one single dose of at least 2x107 allogenic human cord blood mononuclear cells to a human with CP who is 10 years old or younger such that symptoms of CP are decreased in the human---.
Support for --- such that symptoms of CP are decreased in the human--- is found in the Results on pg 24-29.
Claim 25 can be written more clearly as ---wherein the at least one single dose is administered to the human systemically---.
Election/Restrictions
Applicants elected Group I, claims 24-37, without traverse in the reply filed on 06/04/2021.
Claims 24, 25 remain pending and under consideration.
35 USC § 112
Written Description
Claims 24 and 25 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification lacks written description for injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger such that symptoms of CP are decreased as encompassed by claim 24.
Claim 24 encompasses intrathecally (pg 7, para 30, et al.) administering a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP (para 27) who is 10 years old or younger (para 29) such that symptoms of CP are decreased.
Feng of record taught away from injecting a single dose of 2x107 allogeneic human cord blood stem cells intrathecally (which is smaller than “2x107 allogeneic human cord blood stem cells]/kg” as required in claim 24) as follows: “So we deduce that intrathecal infusion and the age in the initiation of treatment (≤10 years old) might be associated with the occurrence of adverse events. This finding potentially demonstrates that the present single dosage (2- 3 × 107/dose) of allogeneic UCBSCs is too large for patients whose age in the initiation of treatment was less than or equal to 10-year-olds who received intrathecal injection in this study” (pg 5, last 8 lines). The specification suggests intravenous or intrathecal injection of a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP (para 27) who is 10 years old or younger (para 29) such that symptoms of CP are decreased.
The examples are limited to injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger intravenously (pg 11, para 51) such that symptoms of CP are decreased (pg 15-17; para 61-73).
While the results on pg 15-17 are limited to intravenous administration (pg 11, para 51), applicants do not provide adequate written description for overcoming the teachings of Feng such that a therapeutic effect would be obtained in favor of or in addition to the deleterious effects described by Feng. Merely suggesting intrathecal administration (pg 7, para 30, et al.) is inadequate written description in light of the teachings of Feng.
It is not readily apparent applicants were in possession of the method of injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger such that symptoms of CP are decreased as encompassed by claim 24.
Enablement
Claims 24 and 25 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intravenously to a human with CP who is 10 years old or younger such that symptoms of CP are decreased, does not reasonably provide enablement for doing so intrathecally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The specification does not enable injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger such that symptoms of CP are decreased as encompassed by claim 24.
Claim 24 encompasses intrathecally (pg 7, para 30, et al.) administering a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP (para 27) who is 10 years old or younger (para 29) such that symptoms of CP are decreased.
Feng of record taught away from injecting a single dose of 2x107 allogeneic human cord blood stem cells intrathecally (which is smaller than “2x107 allogeneic human cord blood stem cells]/kg” as required in claim 24) as follows: “So we deduce that intrathecal infusion and the age in the initiation of treatment (≤10 years old) might be associated with the occurrence of adverse events. This finding potentially demonstrates that the present single dosage (2- 3 × 107/dose) of allogeneic UCBSCs is too large for patients whose age in the initiation of treatment was less than or equal to 10-year-olds who received intrathecal injection in this study” (pg 5, last 8 lines).
The specification suggests intravenous or intrathecal injection of a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP (para 27) who is 10 years old or younger (para 29) such that symptoms of CP are decreased.
The examples are limited to injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger intravenously (pg 11, para 51) such that symptoms of CP are decreased (pg 15-17; para 61-73).
While the results on pg 15-17 are limited to intravenous administration (pg 11, para 51), applicants do not provide adequate written description for overcoming the teachings of Feng such that a therapeutic effect would be obtained in favor of or in addition to the deleterious effects described by Feng. The specification suggests intrathecal administration (pg 7, para 30, et al.); however, given the lack of guidance in the specification taken with Feng, it would have required those of skill undue experimentation to determine that injecting a single dose of 2x107 allogeneic human cord blood stem cells/kg intrathecally to a human with CP who is 10 years old or younger would decrease symptoms of CP as encompassed by claim 24.
35 USC § 103 - Claim Rejections
A) Claims 24, 25 remain rejected under 35 U.S.C. 103 as being unpatentable over Feng (Stem Cells, 2015, Article ID 325652, pg 1-7) as supported by “Average height and Weight Babies to Teenagers” (2023) and Ramanov (EP 2298328).
Feng administered allogeneic umbilical CBMCs to patients with CP intravenously (title, abstract, pg 2, col. 1, 2.2 “Cell infusion and patient monitoring”; pg 2, last partial paragraph for 1-29 years). Intravenous injection is “systemically” as required in claims 24 and 25. The children were 1 year old (pg 2, last partial paragraph) which is less than 10 years old as required in claim 24.
Feng administered 2x107 CBMCs/kg over 4-8 injections as follows: Feng administered 2-3x107 cells/dose 4-8 times (pg 2, section 2.2) to patients with an average mean age of 5.85 (pg 3, Table 1). The average weight of a 5 year old female is 17.92 and a 5 year old boy is 18.37 kg; the average weight of a 6 year old female is 19.96 and a 5 year old boy is 20.64 kg. 2-3x107 cells/injection x 4-8 injections is 8x107 – 1.6x108 cells (see “Average height and Weight Babies to Teenagers”). For a child that is 17.92 kg, that is 8.93x107 cell/kg which is at least 2x107 cells/kg as required in claim 24. The total number of cells per kilogram described by Feng was over 2x107 allogeneic CBMCs/kg.
Feng did not administer one dose of 2x107 cells/kg as required in claim 24. However, it would have been obvious to do administer the cells all at once to decrease visits to the clinic. Those of ordinary skill in the art at the time of filing would have been motivated to reduce the number of doses to one dose to improve efficiency. Modifying the dosage was well within the purview of the ordinary practitioner at the time of filing as evidenced by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to administer one dose of 2x107 cells/kg to patients as required in claim 24 as a matter of optimization.
Ramanov taught “unexpectedly to the authors of this invention, they have discovered that the umbilical cord blood nucleated cells are highly effective if applied as a single injection of umbilical cord blood cells to patients” (pg 8, para 59). Therefore, those of skill would have had a reasonable expectation of successful treatment using a single dose as claimed.
The method of Feng as written MUST inherently result in decreased symptoms of CP including improved motor function for “at least 12 month after administering the single dose” as required in claim 24 because the allogeneic CBMCs, route of administration, and total number of allogeneic CMBCs used by Feng are EXACTLY the same type of cell, route of administration, and number of cells as those used by applicants. Feng taught “Several preclinic and clinic trials now show that allogeneic UCBSCs have therapeutic effects for CP” (pg 1, 2nd para). Therefore, the protocol of Feng without modification MUST inherently result in the therapeutic effect claimed.
Modifying the protocol of Feng to one dose also MUST inherently result in the therapeutic effect claimed because the type of cell, route of administration, dosage schedule, and number of cells are EXACTLY those used by applicants and claimed.
Intravenous administration described by Feng is “systemic” as required in claim 25.
Response to arguments
Applicants argue Feng did not administer one single dose of 2x107 CBMCs/kg as required in claim 24 and teaches away from such a dose because Feng says “In order to provide patients maximal benefits from this treatment, we might increase more injection times, up to 8 times if the patients had no adverse effects in the treatment period” (pg 5). Applicants’ argument is not persuasive. Ramanov taught “unexpectedly to the authors of this invention, they have discovered that the umbilical cord blood nucleated cells are highly effective if applied as a single injection of umbilical cord blood cells to patients” (pg 8, para 59).
The argument is also not persuasive because Feng’s statement is limited to teaching away from intrathecal embodiments encompassed by claim 24. The systemic administration described by Feng without modification MUST inherently result in the therapeutic effect claimed. Modifying the systemic protocol of Feng to one dose also MUST inherently result in the therapeutic effect claimed because the type of cell, route of administration, dosage schedule, and number of cells are EXACTLY those used by applicants and claimed. Moreover, it was well known that systemic administration of at least 2x107 CBMCs/kg to humans 10 years old or younger resulted in a therapeutic effect as described by Lee (of record) who infused 0.6~15.65x107 CBMCs/kg in one dose (pg 3, col. 1, 2nd full para). Therefore, the statement by Feng must be limited to “teaching away” from an intrathecal single dose of 2x107 CBMCs/kg to humans 10 years old or younger because it was well-known that systemic administration of high doses of CBMCs/kg resulted in a therapeutic effect.
B) Claims 24, 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (J. Transl. Med., 2012, Vol. 10, No. 58, pg 1-11) in view of Feng (Stem Cells, 2015, Article ID 325652, pg 1-7) and Ramanov (EP 2298328).
Lee administered autologous umbilical cord blood mononuclear cells to children with cerebral palsy intravenously (title, abstract, pg 2, 1st full paragraph “Intravenous infusion of autologous CBMNC in children with CP represents a novel and safe challenge that may involve a quite different mechanism of action from previous treatment methods”; 23~91 months on pg 3, col. 1, 2nd full paragraph). Intravenous administration described by Lee is “systemic” as required in claim 24.
0.6~15.65x107 CBMCs/kg were infused in one dose (second sentence of “Results”) which is “at least one dose containing at least 2x107 cells/kg” as required in claim 24.
The children were age 23~91 months (pg 3, col. 1, 2nd full paragraph); 23 and 24 months are “10 years old or younger” as required in claim 24.
In Table 1 (pg 4), every “Y” for “Yes” in the chart under “Tx Response” is an indication of “symptoms of CP are treated” as required in claim 24. Specifically, the 23 month old showed “therapeutic responses to autologous cord blood infusions” under the category of PEDI (pediatric evaluation of disability inventory) as indicated by the “Y”. The 24 month old showed “therapeutic responses” under the category of GMFCS as indicated by the “Y”. Lee taught neurological improvement was observed (pg 3, col. 2, 2nd full para). This is all that is required to meet the limitation of “symptoms of CP are treated” in claim 24.
These two children described by Lee MUST inherently have improved “motor function” “at least 12 month after the dose” as required in claim 24 because Lee administered human CBMCs using the exact same total number and dosage used by applicants.
Lee did not teach using allogeneic CBMCs as required in claim 24.
However, Feng administered allogeneic umbilical cord blood stem cells to patients with cerebral palsy intravenously (title, abstract, pg 2, col. 1, 2.2 “Cell infusion and patient monitoring”; pg 2, last partial paragraph for 1-29 years). The children were 1 year old (pg 2, last partial paragraph) which is “10 years old or younger” as required in claim 24. Feng taught “Several preclinic and clinic trials now show that allogeneic UCBSCs have therapeutic effects for CP” (pg 1, 2nd para). The method of Feng MUST inherently result in improved symptoms of CP including motor function for “at least 12 month after the dose” as required in claim 24 because the allogeneic CBMCs and total number of used by Feng are EXACTLY the same as the allogeneic CBMCs and total number of cells used by applicants. Feng administered 2x107 cells/kg over 4-8 injections as follows: Feng administered 2-3x107 cells/dose 4-8 times (pg 2, section 2.2) to patients with an average mean age of 5.85 (pg 3, Table 1). The average weight of a 5 year old female is 17.92 and a 5 year old boy is 18.37 kg. The average weight of a 6 year old female is 19.96 and a 5 year old boy is 20.64 kg. 2-3x107 cells/injection x 4-8 injections is 8x107 – 1.6x108 cells. For a child that is 17.92 kg, that is 8.93x107 cell/kg which is at least 2x107 cells/kg as required in claim 24. Therefore, the total number of cells per kilogram described by Feng was over 2x107 cells/kg.
Thus it would have been obvious to those of ordinary skill in the art at the time of filing to administer CBMCs to a patient with cerebral palsy systemically as described by Lee that are allogeneic as described by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to use allogeneic cells instead of autologous cells because Feng taught allogeneic cells are attractive when children with cerebral palsy have not banked their own umbilical cord blood (pg 3-4, Discussion, paragraph 2) and because Feng taught “allogeneic stem cells may be more beneficial than autologous cells for CP patients” (pg 4, line 6-7).
Intravenous administration described by Lee and Feng is “systemic” as required in claim 25.
Response to arguments
Applicants argue Feng taught away from using allogenic cells because Feng taught “allogeneic stem cells may be more beneficial than autologous cells for CP patients” (pg 4, line 6-7). Applicants’ argument is not persuasive because Feng provided motivation to use allogenic cells instead of the autologous cells of Lee because they are “more beneficial”.
If applicants are attempting to argue Feng taught away from administering the single dose claimed systemically, applicants’ argument is not persuasive. Feng says “In order to provide patients maximal benefits from this treatment, we might increase more injection times, up to 8 times if the patients had no adverse effects in the treatment period” (pg 5). Feng’s statement is limited to teaching away from intrathecal embodiments encompassed by claim 24. Systemic administration of at least 2x107 CBMCs/kg to humans 10 years old or younger resulted in a therapeutic effect as described by Lee (of record) who infused 0.6~15.65x107 CBMCs/kg in one dose (pg 3, col. 1, 2nd full para). Therefore, the statement by Feng must be limited to “teaching away” from an intrathecal single dose of 2x107 CBMCs/kg to humans 10 years old or younger because it was well-known that systemic administration of high doses of CBMCs/kg resulted in a therapeutic effect as described by Lee.
C) Claims 24, 25 remain rejected under 35 U.S.C. 103 as being unpatentable over Yang (J. Transl. Med., 2010, Vol. 8, No. 75, pg 1-6) in view of Lee (J. Transl. Med., 2012, Vol. 10, No. 58, pg 1-11) and supported by “Average height and Weight Babies to Teenagers” (2023).
Yang administered allogeneic CBMCs to patients aged 15-68 (pg 2, 3rd full para) with “degenerative conditions” (title) one of whom had CP (pg 2, Table 1) intrathecally and intravenously (pg 2, “Cell Processing”; pg 3, “Cell administration”). The dose was “2 mls of cell suspension containing 1-3x107 cells” via lumbar puncture and “30 ml intravenous infusion of cell suspension” (pg 3, “Cell Administration”). Assuming each ml contained 1-3x107 cells in the intravenous dose, then 9x108 cells were delivered to each patient. Assuming the average weight of a 15 year old female is 52.16 kg (“Average height and Weight Babies to Teenagers”), Yang administered 1.7x107 cells/kg (9x107 cells/52.16 kg). Therapeutic effect evaluations were still in progress – pg 5, last sentence of conclusion. However, the protocol of Yang MUST inherently have the therapeutic effect in claim 24 because Yang administered human almost the same total number of allogeneic CBMCs used by applicants intrathecally or intravenously.
Yang taught administering one dose of allogeneic 1.7x107 CBMCs/kg to 15 year old with CP but did not teach administering 2x107 CBMCs/kg to children under 10 years of age as required in claim 24.
However, Lee administered one dose of 0.6~15.65x107 CBMCs/kg (second sentence of “Results”) to children with cerebral palsy intravenously (title, abstract, pg 2, 1st full paragraph “Intravenous infusion of autologous CBMNC in children with CP represents a novel and safe challenge that may involve a quite different mechanism of action from previous treatment methods”; 23~91 months on pg 3, col. 1, 2nd full paragraph). Intravenous administration described by Lee is “systemic” as required in claim 24.
In Table 1 (pg 4), every “Y” for “Yes” in the chart under “Tx Response” is an indication of a therapeutic effect. Specifically, the 23 month old showed “therapeutic responses to autologous cord blood infusions” under the category of PEDI (pediatric evaluation of disability inventory) as indicated by the “Y”. The 24 month old showed “therapeutic responses” under the category of GMFCS as indicated by the “Y”. Lee taught neurological improvement was observed (pg 3, col. 2, 2nd full para). This is a therapeutic effect. These two children under 2 years old infused with one dose of 2x107 CBMCs/kg MUST inherently have the therapeutic effect in claim 24 because Lee administered human CBMCs using the exact same total number, dosage, and route of administration used by applicants.
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to administer 1.7x107 CBMCs /kg to humans 15 years old with CP intrathecally and intravenously as described by Yang by administering one dose of 2x107 cells/kg to patients 10 years of age or younger as described by Lee. Those of ordinary skill in the art at the time of filing would have been motivated to administer one dose of 2x107 cells/kg to patients as described by Lee as a matter of optimization. Those of ordinary skill in the art at the time of filing would have been motivated to treat patients under 10 years of age or younger to delay onset of CP.
The combined teachings of Yang and Lee MUST inherently result in the therapeutic effect of claim 24 for reasons set forth above regarding Yang and Lee individually and because the combined teachings of Yang and Lee taught all the limitations claimed.
Yang and Lee taught intravenous administration which is “systemic” as required in claim 25.
Response to arguments
Applicants state ages 15-68 taught by Yang “is well outside the claimed range of 10 years old and younger”. This wildly mischaracterizes Yang because 15 years old taught by Yang is very close to 10 years old encompassed by claim 24.
Applicants state the skilled person would have no reason to combine Yang and Lee “with a reasonable expectation of success, give the focus on completely different cell types” (i.e. allogeneic vs. autologous CMBCs). Again, this statement wildly mischaracterizes the references because it ignores the fact that both references used CMBCs – they have the same potency, are prepared for injection the same, and are delivered via the same route.
Applicants point out Yang is limited to safety and didn’t monitor therapeutic effectiveness. Applicants point is not persuasive. While Yang taught therapeutic effect evaluations were still in progress (pg 5, last sentence of conclusion), the protocol of Yang MUST inherently have the therapeutic effect in claim 24 because Yang administered human almost the same total number of allogeneic CBMCs used by applicants intrathecally or intravenously. Moreover, Lee taught obtaining a therapeutic effect for reasons cited above. The two children under 2 years old infused with one dose of 2x107 CBMCs/kg MUST inherently have the therapeutic effect in claim 24 because Lee administered human CBMCs using the exact same total number, dosage, and route of administration used by applicants. Finally, the combined teachings of Yang and Lee MUST inherently result in the therapeutic effect of claim 24 for reasons set forth above regarding Yang and Lee individually and because the combined teachings of Yang and Lee taught all the limitations claimed.
Applicants point out that Yang only taught one patient with CP. This does not rise to the level of an argument.
Applicants argue Yang is less relevant than Feng or Lee. Applicants’ argument is not persuasive. Yang administered one dose of allogeneic 1.7x107 CBMCs/kg to patients aged 15 (pg 2, 3rd full para) with “degenerative conditions” (title) including one who had CP (pg 2, Table 1) intrathecally and intravenously (pg 2, “Cell Processing”; pg 3, “Cell administration”).
D) Claims 24, 25 remain rejected under 35 U.S.C. 103 as being unpatentable over Jensen (Case Reports in Transplantation, 2016, Article ID 1717426, pg 1-9) in view of Feng (Stem Cells, 2015, Article ID 325652, pg 1-7) and Lee (J. Transl. Med., 2012, Vol. 10, No. 58, pg 1-11).
Jensen treated a 4.5 year old human that had CP with autologous CBMCs intravenously (45.8 mL, cryopreserved, TNC 2.53 × 10𝑒8; age 4.5 years on pg 4, col. 1, section 2.4). 2.53 × 10𝑒8 TNCs (pg 4, col. 2, 1st full paragraph) is at least 2x107 CBMCs/kg as required in claim 24. Jensen improved motor function (pg 4, “Outcome).
Jensen did not teach administering allogeneic CBMCs as required in claim 24. However, Feng administered allogeneic CBMCs to patients with CP intravenously (title, abstract, pg 2, col. 1, 2.2 “Cell infusion and patient monitoring”; pg 2, last partial paragraph for 1-29 years). Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to administer at least 2x107 cells/kg CBMCs to pediatric CP patients and obtain a therapeutic effect as described by Jensen using allogeneic CBMCs described by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to use allogeneic cells instead of autologous cells because Feng taught allogeneic cells are attractive when children with cerebral palsy have not banked their own umbilical cord blood (Discussion, paragraph 2).
Jensen did not teach the patient was 10 years old or younger as required in claim 24. However, Feng administered allogeneic umbilical CBMCs to 1 year old patients with CP (pg 2, last partial paragraph), and Lee treated 23 and 24 patients that have CP with CBMCs injected intravenously (pg 3, col. 1, 2nd full paragraph). Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to administer at least 2x107 cells/kg CBMCs to pediatric CP patients and obtain a therapeutic effect as described by Jensen in a patient that is 10 years old or younger as described by Feng and Lee. Those of ordinary skill in the art at the time of filing would have been motivated to treat patients 10 years old or younger to delay onset of serious disease and prevent death.
Therapeutic effect
The method of Jensen as written MUST inherently result in the therapeutic effect “at least 12 month after the dose” as required in claim 24 because the CBMCs, route of administration, and total number of allogeneic CMBCs used by Feng are EXACTLY the same type of cells, route of administration, dosage schedule, and number of cells described by applicants as being part of the invention. Jensen taught the patient had a “remarkable recovery” (abstract). Therefore, the protocol of Jensen without modification also MUST inherently result in the therapeutic effect claimed.
Jensen taught obtaining a therapeutic effect. Table 1 of Lee taught a therapeutic effect. The combined teachings of Jensen, Feng, and Lee MUST inherently result in the therapeutic effect in claim 24 because two of the references taught therapeutic effects and because the combined references taught all the limitations claimed.
Response to arguments
Applicants argue Jensen is limited to autologous CMBCs. Applicants’ argument is not persuasive because the combined teachings of Jensen, Feng, and Lee taught using allogeneic CBMCs.
Applicants argue Jensen used half as many CMBCs. Applicants’ argument is not persuasive because the combined teachings of Jensen, Feng, and Lee taught using the number of CBMCs claimed.
Applicants argue the Examiner has not provided logic for inherency. Applicants’ argument is not persuasive. Jensen improved motor function (pg 4, “Outcome) which is all that is required to meet the therapeutic effect claimed. In addition, the combined teachings of Jensen, Feng, and Lee also MUST inherently result in the therapeutic effect claimed because they teach the EXACT same type of cells, route of administration, dosage schedule, and number of cells claimed. This is all the logic that is required.
Applicants argue Lee does not paint a rosy picture in Table 1 (pg 4). Applicants’ statement wildly misconstrues the reference. All of the “Y”s in Table 1 are therapeutic effects. Lee concludes “CB infusion is safe and feasible, and has yielded potential benefits in children with CP” (abstract “Conclusions”).
Applicants argue Yang is limited to safety. Applicants’ argument is not persuasive. Jensen taught obtaining a therapeutic effect. Table 1 of Lee taught a therapeutic effect. The combined teachings of Jensen, Feng, and Lee MUST inherently result in the therapeutic effect in claim 24 because two of the references taught therapeutic effects and because the combined references taught all the limitations claimed.
E) Claim 24, 25 remain rejected under 35 U.S.C. 103 as being unpatentable over Meier (Pediatric Res., 2006, Vol. 59, pg 244-249) in view of Feng (Stem Cells, 2015, Article ID 325652, pg 1-7) as supported by Rumajogee (Front. Neurology, 2016, Vol. 7, No. 57, pg 1-20).
Meier administered human CBMCs to rats with cerebral hypoxic-ischemic damage caused by ligation of the left common carotid artery followed by systemic hypoxia (pg 244, col. 2, “hUCB-derived mononuclear cells”; pg 245, col. 1, “Cerebral Ischemia”, “Experimental Protocol”). The CBMCs were administered intraperitoneally (pg 245, col. 1, 4th full para, line 7). The hypoxic-ischemic rat has “cerebral palsy” as required in claim 24 because Rumajogee taught this rat is a model of cerebral palsy (abstract).
Meier did not teach administering at least 2x107 allogeneic CBMCs/kg to a human with CP who is 10 years old or less as required in claim 24.
However, it was well-known to administer allogeneic CBMCs to human patients with CP who are 1 year old intravenously as described by Feng (title, abstract, pg 2, col. 1, 2.2 “Cell infusion and patient monitoring”; pg 2, last partial paragraph for 1-29 years; pg 2, last partial paragraph).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to administer human CBMCs to mammal that has CP as described by Meier and administering allogeneic CBMCs to human patients with CP who are 1 year old intravenously as described by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to use allogeneic CBMCs instead of autologous CBMCs because Feng taught allogeneic cells are attractive when children with cerebral palsy have not banked their own umbilical cord blood (Discussion, paragraph 2). Those of ordinary skill in the art at the time of filing would have been motivated to treat patients under 10 years of age to delay progression of CP.
Feng administered 2x107 CBMCs/kg over 4-8 injections for reasons set forth in rejection A) above. Feng did not administer one dose of 2x107 cells/kg as required in claim 24. However, it would have been obvious to do administer the cells all at once systemically to decrease visits to the clinic. Those of ordinary skill in the art at the time of filing would have been motivated to reduce the number of doses to one dose to improve efficiency. Modifying the dosage was well within the purview of the ordinary practitioner at the time of filing as evidenced by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to administer one dose of 2x107 cells/kg systemically to patients as required in claim 24 as a matter of optimization.
Therapeutic effect
The method of Feng alone MUST inherently result in the therapeutic effect in claim 24 because the allogeneic CBMCs, route of administration, and total number of allogeneic CMBCs used by Feng are EXACTLY the same type of cell, route of administration, and number of cells as those used by applicants. Feng taught “Several preclinic and clinic trials now show that allogeneic UCBSCs have therapeutic effects for CP” (pg 1, 2nd para). Therefore, the protocol of Feng without modification MUST inherently result in the therapeutic effect claimed.
Modifying the protocol of Feng to one dose also MUST inherently result in the therapeutic effect claimed because the type of cell, route of administration, dosage schedule, and number of cells are EXACTLY those used by applicants and claimed.
Intravenous administration described by Feng is “systemic” as required in claim 25.
Response to arguments
Applicants argue Meier did not teach the species, dosage or age in claim 24. Applicants’ argument is not persuasive. The combined teachings of Meier and Feng taught all the limitations claimed for reasons set forth above.
Applicants argue motivation has not been provided. Applicants’ argument is not persuasive. Those of ordinary skill in the art at the time of filing would have been motivated to reduce the number of doses to one dose to improve efficiency. Modifying the dosage was well within the purview of the ordinary practitioner at the time of filing as evidenced by Feng. Those of ordinary skill in the art at the time of filing would have been motivated to administer one dose of 2x107 cells/kg systemically to patients as required in claim 24 as a matter of optimization.
Conclusion
No claim allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638