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 amended claims filed on July 29, 2026, have been acknowledged. Claims 2, 6-7, 9, 15-16, 18-19, 22, and 26 were cancelled. Claims 1, 11, 20-21, and 23-24 were amended. Claim 27 is new. Claims 1, 3-5, 8, 10-14, 17, 20-21, 23-25, and 27 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 62/889,225, filed on August 20, 2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 3-5, 8, 10-14, 17, 20-21, 23-25, and 27 receive domestic benefit from U.S. provisional application No. 62/889,225, filed on August 20, 2019.
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.
Claims 1, 3-5, 8, 10-14, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 2006/0275271 (Chow; corresponds to US Patent No. 8048619) further in view of Borlongan et al. (Stroke 35: 2385–2389. 2004), as evidenced by Jaime-Perez et al. (Rev Bras Hematol Hemoter. 38: 88–89. 2016) and Lindsberg et al. (Stroke. 34: 2518-2532. 2003). This is a new rejection substantially similar to a previous rejection made in response to Applicant’s amendments to claim 1. Any aspect of Applicant’s traversal that is relevant to the newly recited rejection of record is addressed below.
Regarding claims 1 and 17, Chow teaches a method of treating brain injury (stroke) by administering plasma-depleted umbilical cord blood to a human subject (abstract and paragraphs 0016 and 0112). Lindberg evidences that inflammatory responses and stroke are strongly linked (whole document) and identifies that in case-control studies, acute infection (which causes an inflammatory response) within the preceding week was a trigger factor for ischemic stroke (abstract). Furthermore, dependent claim 20 claims that the subject has a stroke score, further identifying stroke as a brain injury induced by inflammation.
Examples 7-8 teach that this procedure can include pre-medication regimens including administering mannitol (a blood-brain-barrier permeabilizer) (paragraphs 0220 and 0241).
Chow teaches that the plasma-depleted UCB units of the present invention meet the following selection criteria: a minimum of 4/6 HLA A/B/DR matches at high resolution (paragraph 0073). Furthermore, Chow teaches that they treated multiple patients with 5/6 or 6/6 HLA matches (Table 5).
Chow is silent as to whether the plasma-depleted umbilical cord blood contain IL-10 at levels higher than IL-1 beta, IL-2, IL-6, IFN gamma, or TNF-alpha.
However, the instant specification discloses that in Examples 1-3, they received plasma depleted umbilical cord blood from Stemcyte’s public cord blood bank and assayed them to examine IL-10, IL-1 beta, IL-2, IL-6, IFN gamma, and TNF-alpha expression levels. Example 1 and Table A disclose that plasma depleted umbilical cord blood IL-10 at levels higher than IL-1 beta, IL-2, IL-6, IFN gamma, or TNF-alpha. The specification discloses that the plasma depletion umbilical cord blood method corresponds to the method disclosed in US8048619 (the Patent of USPGPub 2006/0275271 cited above) and specifically identifies the method of US8048619 as a method that produces the plasma-depleted, non-RBC-depleted UCB units of the present invention (Examples 1-3, Table A, page 5, line 27-page 6, line 24, page 14, line 28-page 15, line 8).
Therefore, the plasma depleted umbilical cord blood of Chow is considered to inherently generate plasma depleted umbilical cord blood with IL-10 at levels higher than IL-1 beta, IL-2, IL-6, IFN gamma, and TNF-alpha. Furthermore, MPEP 2112(I) states that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
Additionally, MPEP2112(II) states that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.
Although Chow teaches that their method can include pre-medication regimens including administering mannitol (a blood-brain-barrier permeabilizer), they do not teach wherein the blood-brain barrier permeabilizer is administered after administration of the umbilical cord blood.
However, Borlongan teaches a method of treating stroke by co-administering human umbilical cord blood (HUCB) with mannitol. HUCB–mannitol treatment significantly increased brain levels of neurotrophic factors, which correlated positively with reduced cerebral infarcts and improved behavioral functions (abstract). During the 1-hour occlusion of the middle cerebral artery (MCA), anesthetized animals received intravenous (jugular vein) injection of HUCB (200 000 cells) over 10 minutes. Immediately thereafter, using the same intravenous line, animals received 1.1 mol/L mannitol (maintained at 4°C) or over 5 minutes (page 2386, column 1m, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating stroke by administering umbilical cord blood of Chow by administering the mannitol after infusion of the umbilical cord blood, as identified by Borlongan, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to modify with a reasonable expectation of success because both Chow and Borlongan teach administering umbilical cord blood and mannitol to stroke patients and Borlongan teaches that administering human umbilical cord blood (HUCB) then mannitol significantly increased brain levels of neurotrophic factors, which correlated positively with reduced cerebral infarcts and improved behavioral functions. As such, it would have been obvious that mannitol could be administered after the umbilical cord blood of Chow as this was shown to be an effective treatment in stroke patients. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claims 3-4, Chow teaches that the UCB [umbilical cord blood] further comprises a cryoprotectant , such as DMSO (paragraph 0012).
Regarding claim 5, Chow teaches that the umbilical cord blood (UCB) compositions of the present invention possess the advantageous features of having plasma that is substantially depleted but red blood cells (RBC) that are not depleted from the UCB unit, i.e., a plasma-depleted, non-red blood cell-depleted composition (paragraph 0009).
Regarding claim 8, Examples 7-8of Chow teach procedures for thawing plasma-depleted, cryopreserved cord blood that was stored.
Regarding claim 10, Examples 7-8 of Chow teach procedures for thawing plasma-depleted, cryopreserved cord blood including using a water bath at a temperature of 37°C ± 2°C. The water in the water bath must maintain this temperature throughout the thaw procedure (paragraphs 0205 and 0225).
Regarding claim 11, Example 7 of Chow teaches that the thawed cord blood is not washed before infusion.
Regarding claim 12, Example 8 of Chow teaches that the thawing to transport to infusion process should be completed within 60 minutes.
Regarding claim 13, Chow teaches that they administered a total nucleated cell (TNC) dose of 4.8 x 107 cells/kg-1.5 x 108 cells/kg (Table 5). Jaime-Perez evidences total mononuclear cells are roughly half of the total mononucleated cells (page 88, column 1, paragraph 3). Thus, the mononuclear cell totals equate to 2.4 x 107 cells/kg-0.75 x 108 cells/kg. The specification discloses that "approximately" means within an acceptable range for the particular value as determined by one of ordinary skill in the art. Based on this definition, the dosing of Chow is considered to fall within approximately 1 x 108 cells/kg.
Regarding claim 14, Examples 7-8 of Chow teach that they administer the umbilical cord blood through infusion.
Response to Arguments
Applicant's arguments filed July 29, 2026, are acknowledged.
Applicant argues that the cited references don’t teach the all of the limitations of the amended claim 1. Specifically, Applicant argues that the cited references fail to disclose or suggest treating a human subject and that the results obtained in rat models of Borlongan do not necessarily translate into humans, particularly given the vast differences in scale, immune system, and brain physiology (page 5, paragraph 4-page 6, paragraph 2).
Applicant's arguments have been fully considered but they are not persuasive.
As stated in the rejection above, Chow teaches that their method can be used to treat human subjects (paragraph 0016). Furthermore, although Borlongan performs their model in rats, rats are a well known animal model for developing pre-clinical methods that could be translated to treat human diseases. Furthermore, as stated in the rejection above, Borlongan teaches that they are usually human umbilical cord blood cells. The primary reason to use human umbilical cord blood cells is as a preclinical model for translation to human treatment methods. Applicant has not provided any additional evidence or support for their position that the results of Borlongan, specifically, cannot be translated to human treatment methods. Therefore,, Applicant’s argument regarding translation of Borlongan’s rat models to human, this is considered arguments of counsel. Arguments of counsel cannot take the place of factually supported objective evidence in the record. See In re Schulze, 346 F.2d 500, 602, 145 USPQ 716, 718 (CCPA 1965), In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Thus, Attorney statements regarding the rat models of Borlongan do not necessarily translate into humans, are not evidence without a supporting declaration.
Applicant further argues that Chow is entirely silent with respect to administering to a human subject a BBB permeabilizer composition after administration of a therapeutic composition comprising umbilical cord blood (UCB) as recited in amended claim 1. Instead, Chow describes administering mannitol to a subject before administration of plasma-depleted UCB as part of a pre-medication regimens. In particular, Chow uses mannitol for an entirely different purpose (mitigating infusion side effects) than that of amended claim 1 (i.e., enhancing BBB permeability for therapeutic benefit after UCB administration). Thus, Chow teaches away from using mannitol after administering the UCB cells.
Applicant argues that Borlongan does not cure the deficiencies of Chow. First, Borlongan administered mannitol immediately after a subtherapeutic HUCB dose (200,000 cells) during active arterial occlusion in a rat model. This is fundamentally different from the method of amended claim 1, where after administration of the therapeutic composition the human subject is further administered with a blood-brain barrier (BBB) permeabilizer composition.
Thus, the method of amended claim 1 differs from Borlongan in three critical respects: (i) human versus rat subjects, (ii) a therapeutic versus subtherapeutic dose, and (iii) administration of the BBB permeabilizer after administration of the therapeutic composition rather than immediately during cell delivery. Furthermore, Borlongan concluded that "HUCB cells did not cross the BBB with or without mannitol treatment." Thus, one of skill in the art would not have had a motivation to apply Borlongan acute-phase rat protocol for HUCB cell transplantation to enhance cell delivery in Chow's methods, nor would there have been a reasonable expectation of success in doing so. (page 5, paragraph 4-page 6, paragraph 2).
Applicant's arguments have been fully considered but they are not persuasive.
As an initial matter, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding Applicant’s arguments against Chow, although Chow teaches using a pre-medication regimen with mannitol for mitigating infusion side effects, there is nothing in Chow that directly teaches against administering mannitol after administering the UCB cells. One of ordinary skill in the art would understand that mannitol could be used as part of a pre-medication regimen to manage infusion side effects while also administering mannitol after administering the UCB cells to act as a blood brain barrier permeabilizer. As recited in the rejection above, Borlongan teaches a method of treating stroke by co-administering human umbilical cord blood (HUCB) with mannitol. HUCB–mannitol treatment significantly increased brain levels of neurotrophic factors, which correlated positively with reduced cerebral infarcts and improved behavioral functions (abstract). During the 1-hour occlusion of the middle cerebral artery (MCA), anesthetized animals received intravenous (jugular vein) injection of HUCB (200 000 cells) over 10 minutes. Immediately thereafter, using the same intravenous line, animals received 1.1 mol/L mannitol (maintained at 4°C) or over 5 minutes (page 2386, column 1m, paragraph 2). Therefore, there is a clear therapeutic reason for administering mannitol after administering the UCB cells as this improves recovery after an acute stroke.
Regarding Applicant’s arguments against Borlongan about the timing of administration of the UCB cells and mannitol, it is noted that there is no timeframe associated with when the mannitol is delivered after administering the UCB cells in claim 1. Therefore, the broadest reasonable interpretation would include administering mannitol immediately after the UCB cells are delivered. Although Applicant considers their claimed method to require administrating of the BBB permeabilizer after administration of the therapeutic composition rather than immediately during cell delivery as they suggest occurs in Borlongan, it is not entirely clear what distinction Applicant is trying to argue. As identified in the rejection above, Borlongan teaches during the 1-hour occlusion of the middle cerebral artery (MCA), anesthetized animals received intravenous (jugular vein) injection of HUCB (200 000 cells) over 10 minutes. Immediately thereafter, using the same intravenous line, animals received 1.1 mol/L mannitol (maintained at 4°C) or over 5 minutes (page 2386, column 1m, paragraph 2). As such, based on the recited method of Borlongan, mannitol was delivered after cells were fully administered and not concurrently (i.e. immediately during cell delivery) as argued by the Applicant.
Applicant’s arguments regarding the translation of rat models to human treatment methods has been addressed above.
Regarding Applicant’s arguments about the “subtherapeutic dose” used by Borlongan, it is worth noting that claim 1 does not require a specific dose of UCB cells to be administered and when Borlongan discuses a subtherapeutic dose, they appear to be referencing the fact that other methods use higher doses (>500,000 cells) rather than the fact that they didn’t achieve a therapeutic response with their dose. In actuality, Borlongan identifies that their cells did achieve a therapeutic effect even at the lower dose similar to those seen with higher doses (page 2388, column 2, paragraph 4).
Regarding Applicant’s argument that Borlongan teaches that HUCB cells did not cross the BBB with or without mannitol treatment, it is worth noting that in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., HUCB cells must cross the BBB) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claims do not require that the UCB cells cross the blood brain barrier, only that a therapeutically effective amount is administered to the patient. Borlongan specifically teaches that the HUCB cells were able to have a therapeutic effect as a perturbed BBB permeability produced by mannitol was shown critical for mobilizing graft-derived trophic factors to be present in the circulating blood, as well as the brain to exert neuroprotection (page 2388, column 2, paragraph 4-page 2389, column 1, paragraph 2).
Therefore, the art clearly provides motivation for delivering mannitol as a blood brain barrier permeabilizer after delivering the UCB cells with a reasonable expectation of success.
Applicant further argues the method of claim 1 exhibits unexpected results. These unexpected results were submitted in the previously filed response dated October 10, 2025. Notably, use of the recited UCB composition to treat a human patient with acute ischemic stroke resulted in "significant recovery" and this recovery "is unprecedented and has not [been] observed in other clinical trials." See Specification, Example 3. Specifically, this patient's "NIHSS improved from 9 point at baseline to 1 point at 12 months post-CB transfusion (FIG. 4A), Berg balance score from 0 point to 48 point (FIG. 4B), and Barthel index score from 0 point to 90 point (FIG. 4C)." (page 7, paragraph 3).
Applicant's arguments have been fully considered but they are not persuasive.
Although Applicant argues unexpected results, the claims are not commensurate in scope with the experimental results cited by the Applicant. MPEP 716.02(d) discloses that whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
Regarding the claims at issue in the instant application, claim 1 does not require that the patient has a specific NIHSS score, a specific recovery in the patients within a specific time frame ,an HLA match of 6/6, a specific dose of UCB cells (2.63 x 108) and 4 doses of mannitol beginning 1 hour after the UCB infusion (see specification page 40). Furthermore, claim 1 is broader than the cited results as claim 1 claims using either PD-UCBs or RCR-UCBs while the claimed unexpected results only discuss using PD-UCBs.
As such, the claims as written are not commensurate in scope with alleged unexpected results.
Additionally, it is not clear that these results would be unexpected as Chow inherently has the same cytokine profile as claimed in claim 1 and showed that administering PD-UCBs was safe and effective (Example 4). Furthermore, Laskowitz identifies multiple patients that achieved a similar reduction (9 to 1 in Applicant’s patient, i.e. an 8 point improvement) on their NIHSS score (11 to 3, i.e. an 8 point improvement) by 3 months. Thus, these are not considered unexpected results.
Note that unexpected results must be “really unexpected” in view of the prior art. “Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected.” (emphasis added). See MPEP §716.02.
In view of the foregoing, applicant’s arguments pertaining to unexpected results are not found persuasive.
Claims 1, 20, 24-25, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 2006/0275271 (Chow; corresponds to US Patent No. 8048619) further in view of Borlongan et al. (Stroke 35: 2385–2389. 2004) as applied to claims 1 and 18 above, and further in view of Laskowitz et al. (Stem Cells Translational Medicine 7: 521–529. 2018; referenced in IDS). This is a new rejection made in response to Applicant’s new claim 27 that is substantially similar to a previous rejection of record. Applicant’s traversal has been addressed above.
Regarding claim 20, the teachings of Chow and Borlongan are as discussed above.
Chow is silent as to determining the NIHSS score of the stroke patients administered the cord blood.
However, Laskowitz teaches a method of administering umbilical cord blood to patients following ischemic stroke. Patients had a NIHSS score of 9-14 (abstract and page 524, column 2, paragraphs 1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of treating stroke by administering umbilical cord blood of Chow and Borlongan could be used with the NIHSS patient population parameters of Laskowitz to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to treat this patient population with a reasonable expectation of success because Chow, Borlongan, and Laskowitz teach administering umbilical cord blood to stroke patients. As such, it would have been obvious that the patient population of Laskowitz could also be treated by the method of Chow and Borlongan. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claims 24-25, the teachings of Chow and Borlongan are as discussed above.
Chow is silent as to the subject not being administered TPA before administering the umbilical cord blood.
However, Laskowitz teaches that when administering TPA, there is a short window for administering TPA to patients following ischemic stroke as well as a risk of increased bleeding. As such, TPA is only used in about 20% of patients with ischemic stroke, and cannot be used to treat hemorrhagic stroke (page 522, column 1, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of treating stroke by administering umbilical cord blood of Chow and Borlongan could be used in patients that have not received TPA before administering the umbilical cord blood, as identified by Laskowitz to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to treat this patient population with a reasonable expectation of success because Chow broadly teaches administering umbilical cord blood to stroke (which would include ischemic and hemorrhagic stroke patients) patients and does not identify their patient population as only being ones that received TPA. Furthermore, as Laskowitz teaches that only 20% of patients with ischemic stroke and none with hemorrhagic stroke are administered TPA and there is a distinct risk of increased bleeding, it would have been obvious to use the method of Chow and Borlongan to treat stroke patient populations that were not treated with TPA. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 27, as an initial matter, the claim limitation, “wherein the BBB permeabilizer composition is administered to the human subject at least about 30 minutes after administration of the therapeutic composition”, is broadly interpreted to include administering the BBB permeabilizer at least 30 minutes after the start of administration of the UCB cells as applicant has not defined whether the “after administration” refers to the start or end of administration of the UCB cells.
the teachings of Chow and Borlongan are as discussed above. As stated supra, Borlongan teaches during the 1-hour occlusion of the middle cerebral artery (MCA), anesthetized animals received intravenous (jugular vein) injection of HUCB (200 000 cells) over 10 minutes. Immediately thereafter, using the same intravenous line, animals received 1.1 mol/L mannitol (maintained at 4°C) or over 5 minutes (page 2386, column 1m, paragraph 2).
Chow and Borlongan do not teach wherein the BBB permeabilizer composition is administered at least 30 minutes after administration of the therapeutic composition.
However, Laskowitz teaches that they administered UCB cells to stroke patients using a peripheral IV over a period of 30 minutes (page 523, column 2, paragraph 2).
Therefore, Borlongan already teaches that mannitol can be administered using the same intravenous line after HUCB infusion and Laskowitz teaches that infusion of UCB cells to human stroke patients can take 30 minutes. Therefore, it would have been well understood by one of ordinary skill in the art that the infusion of mannitol can occur at least 30 minutes after the start of administering the UCB cells as the infusion of UCB cells can take 30 minutes, necessitating that the mannitol is delivered at least 30 minutes after the start of the infusion of the UCB cells.
Claims 1 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 2006/0275271 (Chow; corresponds to US Patent No. 8048619) further in view of Borlongan et al. (Stroke 35: 2385–2389. 2004) as applied to claim 1 above, and further in view of Niranjan et al. (Restorative Neurology and Neuroscience 17: 22-30. 2018). This rejection is repeated with regards to the rejection recited in the Non-final Office action mailed on May 5, 2026. Applicant’s traversal has been addressed above.
The teachings of Chow and Borlongan are as discussed above. Chow teaches that transfusion of large volumes of major ABO incompatible red blood cells is known to cause transfusion reactions in patients who have a significant titer of anti-A and/or anti-B (paragraph 0219),
Chow and Borlongan do not teach that their PD-UCBs are ABO compatible.
However, Niranjan teaches that the utility and safety of ABO compatible non identical blood components is well known and their use is advocated and practiced worldwide. Furthermore, Niranjan identifies multiple scenarios in which using ABO compatible blood can be beneficial to the patient, including instances in which the blood group of the patients is not known or not confirmed (page 34, paragraphs 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered ABO compatible PD-UCB in the method of treating stroke of Chow and Borlongan to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use ABO compatible PD-UCB with a reasonable expectation of success because Chow identifies that there are known risks associated with using non-compatible PD-UCB and Niranjan identifies multiple potential scenarios where using compatible blood benefits the patient, including when the blood group of the patients is not known or not confirmed. Furthermore, Niranjan identifies that using ABO compatible blood is a common practice world wide. Therefore, considering the risks, it would have been obvious that one can use ABO compatible PD-UCB as this is a common practice and to avoid the risks, especially in the scenarios identified by Niranjan. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 1 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 2006/0275271 (Chow; corresponds to US Patent No. 8048619) further in view of Borlongan et al. (Stroke 35: 2385–2389. 2004) as applied to claim 1 above, and further in view of Yu et al. (Restorative Neurology and Neuroscience 27: 41–54. 2009). This rejection is repeated with regards to the rejection recited in the Non-final Office action mailed on May 5, 2026. Applicant’s traversal has been addressed above.
The teachings of Chow and Borlongan are as discussed above.
Chow and Borlongan do not teach administering immunosuppressive agents to the subject.
However, Yu teaches that treating stroke patients with human umbilical cord blood cells with immunosuppressive agents, such as cyclosporin A, was known. Furthermore, Yu teaches that cyclosporin A is known to exert neuroprotection against ischemia (page 49, column 2, paragraph 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined administering umbilical cord blood in the method of treating stroke of Chow and Borlongan with administering an immunosuppressive agent, such as cyclosporin A, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because both the umbilical cord blood and immunosuppressive agents are known to exert neuroprotective effects in stroke patients and have been used together previously. As such, it would have been obvious to combine administering umbilical cord blood with administering immunosuppressive agents to treat stroke patients. Furthermore, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Conclusion
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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/KEENAN A BATES/Examiner, Art Unit 1631
