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 .
1. Claims 16, 20-22, 24, and 26-28 have been cancelled.
Claims 1-15, 17-19, 23, and 25 are pending and under examination.
Claim Objections
2. Claim 1 is objected to because of the recitations: “a blood sample” (line 3); “a density” (line 6); and “non-red blood cell blood components” (lines 4 and 8). Correction to: “the blood sample”; “the density”; and “the non-red blood cells” is required.
3. Claim 17 is objected to because of the recitations: “a PRP sample” (line 3); “non-red blood cell blood components” (lines 4-5); “one or more non-red blood cell blood components” (lines 7-8); and “the PRP sample” (line 9). Correction to: “the PRP sample”; “the non-red blood cells”; “one or more non-red blood cells”; and “the one or more non-red blood cells” is required.
4. Claim 23 is objected to because of the recitations: “non-red blood cell blood components” (lines 3-4 and 6-7); “a blood sample” (line 4); and “a density” (line 5). Correction to: “the non-red blood cells”; “the blood sample”; and “the density” is required.
5. Claim 25 is objected to because of the recitations: “non-red blood cell blood components”. Correction to: “the non-red blood cells” is required.
Claim Rejections - 35 USC § 103
6. 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.
7. Claims 1, 8-10, 12-15, 17, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron et al. (U.S. 10,617,812), in view of both Maehara et al. (Int. J. Mol. Sci. 2021, 22: 1-16) and Lapointe et al. (WO 12/054975).
Esteron et al. teach: (1) a system for isolating platelet-rich plasma (PRP); the system is closed to avoid contamination and comprises a tube (isolation container) containing ADC (anticoagulant) and a separation gel (physical barrier) having a density of 1.04-1.09 g/cm3; and (2) using the system to isolate PRP by drawing a blood sample from a patient into the tube and centrifuging the tube at 300-2000 g for 10-30 min to obtain a PRP layer above the separation gel and RBCs below the separation gel (claims 1, 8, 12, 17, and 23) (see Abstract; column 5, lines 6-20; paragraph bridging columns 5 and 6; column 7, lines 23-25; 32-42; and 62-67; paragraph bridging columns 8 and 9; column 11, lines 7-32 and 53-63; paragraph bridging columns 12 and 13).
Esteron et al. do not teach isolating exosomes via shear stress generated with zirconium beads (claims 1, 9, 17, and 23). Maehara et al. teach the potential for exosomes isolated from PRP as a novel point-of-care treatment or biomarkers for joint diseases (see Abstract; p. 2, third and fourth paragraphs; p. 5, first full paragraph; p. 7, second and third full paragraphs). Lapointe et al. teach that plasma could be enriched in exosomes if it is subjected to shear stress generated by agitation in suspension in the presence of small beads, such as zirconium beads; agitation takes place by using an agitator (claim 25) (see paragraph bridging p. 5 and 6; p. 7, lines 7-17; paragraph bridging p. 8 and 9; p. 9, lines 2-5; p. 14, lines 30-33; paragraph bridging p. 15 and 16; p. 16, lines 10-23 and 26-27; paragraph bridging p. 17 and 18; p. 24, lines 4-24; p. 51, lines 3-5). Based on these teachings, one of skill in the art would have reasonably concluded that the system and method of Esteron et al. could be further used for the point-of-care isolation of exosomes from PRP. While Lapointe et al. do not specifically trach a density for the zirconium beads, one of skill in the art would have reasonably concluded that enriching the PRP in exosome by using shear stress with zirconium beads would require colocalization of the PRP and beads upon centrifugation. One of skill in the art would have found obvious to modify Esteron et al. by also including in the tube zirconium beads having a lower density than the separation gel (claim 23) and further using the resultant tube in a method for isolating PRP exosomes from a subject’s blood by drawing the blood in the tube, centrifuging the tube to obtain a layer of PRP and zirconium beads above the separation gel, and agitating the tube by using the agitator, to achieve the predictable result of enriching the PRP in exosomes.
With respect to claim 10, one of skill in the art would have found obvious to use routine experimentation and vary the density of the zirconium beads with the reasonable expectation that doing so would identify the optimal density for generating shear stress, and thus, exosomes. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed density was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
With respect to claim 13, centrifugation at 300-2000 g for 10-30 min overlaps with the claimed centrifugation at 1000-1500 g for10-20 min. As per MPEP 2144.05:
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
With respect to claims 14 and 15, the cited prior art does not teach generating the shear stress at an angle. However, MPEP 2144.05 III A states that: "[a] modification of a process parameter may be patentable if it produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In this case, there is no evidence of a difference in kind or even degree over the cited prior art.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
8. Claims 1, 6-10, 12-15, 17, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron et al. taken with both Maehara et al. and Lapointe et al., in further view of Carrol et al. (WO 22/250969).
The teachings of Esteron et al., Maehara et al., and Lapointe et al. are applied as above for claims 1, 8-10, 12-15, 17, 23, and 25. Esteron et al., Maehara et al., and Lapointe et al. do not specifically teach that the tube is made of plastic or glass (claim 6), nor do they specifically teach that the separation gel is thixotropic (claim 7). Carrol et al. teach that collection tubes used for blood processing can be made of glass or plastic and that a thixotropic gel having a density of 1.055-1.080 g/cm3 can be used as the separation gel (see [0001]; [0008]; [0036]; [0075]-[0077]; [0105]). One of skill in the art would have found obvious to use a glass or plastic tube containing a thixotropic separation gel having a density of 1.055-1.080 g/cm3, to achieve the predictable result of obtaining PRP for exosome isolation.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
9. Claims 1, 8-15, 17, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron et al. taken with both Maehara et al. and Lapointe et al., in further view of Marx et al. (Implant Dentistry, 2001, 10: 225-228).
The teachings of Esteron et al., Maehara et al., and Lapointe et al. are applied as above for claims 1, 8-10, 12-15, 17, 23, and 25. Although Esteron et al. teach ACD, Esteron et al. do not specifically teach that ACD is ACD-A (claim 11). Marx et al. teach that ACD-A is the anticoagulant which best supports platelet viability (see paragraph bridging p. 227 and 228). One of skill in the art would have found obvious to use ACD-A as the anticoagulant, to achieve the predictable result of obtaining enhanced exosome yields.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
10. Claims 1-5, 8-10, 12-15, 17-19, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron et al. taken with both Maehara et al. and Lapointe et al., in further view of Gheinani et al. (Scientific Reports, 2018, 8: 1-17).
The teachings of Esteron et al., Maehara et al., and Lapointe et al. are applied as above for claims 1, 8-10, 12-15, 17, 23, and 25. Esteron et al., Maehara et al., and Lapointe et al. do not teach filtering (claims 2-5, 18, and 19). However, Maehara et al. teach that therapy and diagnosis require isolated exosomes (see p. 4, last paragraph; p. 7, second full paragraph). Lapointe et al. teach that, in case a pure exosome population is required, further separation steps can be performed (see p. 18, lines 10-11). Furthermore, Gheinani et al. that using a 0.22 µm filter removes larger particles and results in a filtrate enriched in exosomes (see p. 2, Results-Experimental Design; p. 4, sixth paragraph; p. 6C and D, Fig. 3; p. 12, last paragraph). One of skill in the art would have found obvious to further use filtration as taught by Gheinani et al., to achieve the predictable result of isolating the exosomes from the exosome-enriched PRP.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
11. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/ Primary Examiner, Art Unit 1633
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