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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 23, 2025, has been entered.
Election/Restrictions
Applicant’s election with traverse of Group I (Claims 1-15; drawn to a method of producing a particulated tissue) in the reply filed on November 5, 2024, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Applicant further elected without traverse the following species:
The genus of method steps for producing particulated tissue with an isotonic solution of claim 1.
In light of the Applicant’s elected invention and species, claims 2 and 16-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
DETAILED ACTION
The amended claims filed on September 23, 2025, have been acknowledged. Claim 6 was cancelled. Claims 1 and 7-13 were amended. In light of the Applicant’s elected group and species, claims 2 and 16-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 3-5, and 7-15 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 62/838,245, filed on April 24, 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, and 7-15 receive domestic benefit from U.S. provisional application No. 62/838,245, filed on April 24, 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, 7-11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Shalini et al. (Regenerative Research 2: 41-49. 2013) and United States Patent Application No. 20180044629 (Qin), as evidenced by Lopes et al. (Viruses 7: 27-36. 2014), Noor et al. (International Food Research Journal 19: 869-876. 2012), Scanlon et al. (JOURNAL OF MATERIALS SCIENCE 30: 2577-2583. 1995), and United States Patent No. 10213420 (Hartman).This rejection is substantially similar to a previous rejection of record. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
As an initial matter, it is noted that the specification has not provided a special definition for a rotor mill. Therefore, the art is examined for assessing the broadest reasonable interpretation of the term rotor mill. Lopes evidences that rotor-stator homogenizers can be considered mills and would, thus, also be a rotor mill (page 29, paragraph 4). Furthermore, Noor (page 870, column 1, paragraph 3) and Scanlon (whole document) evidences that blender can also be considered mills. As blenders include a rotor, they are also considered to fall under the broadest reasonable interpretation of a rotor mill. Therefore, the homogenizer of Shalini and the blender (Example 7) of Qin are considered to be rotor mills.
Regarding claim 1, Shalini teaches a method of producing a particulated tissue comprising
obtaining a soft tissue sample (placenta samples were collected upon delivery from normal term pregnancies);
mincing the tissue sample to produce a minced tissue (placenta tissue was manually minced);
milling the minced tissue in the processing chamber into the particulated tissue (tissues were mechanically dissociated using a homogenizer (considered to fall under a rotor mill, as identified above) at 9000 rpm); and
collecting the particulated tissue (After homogenization, cells were filtered and washed and the single cell suspension was resuspended in MSC complete medium) (page 42, column 1, paragraph 5-column 2, paragraph 1).
The tissues of Shalini do not undergo freezing (page 42, column 1, paragraph 5-column 2, paragraph 1) and Figure 1 shows that the particulated tissues comprise viable cells (MSCs).
Shalini does not teach wherein an isotonic solution was added to a processing chamber for the homogenization step.
However, Qin teaches a method of producing particulated tissue comprising:
obtaining a soft tissue sample (Human placenta was obtained from Caesarean section with donor consent);
mincing the tissue sample to produce a minced tissue (the placental membrane was cut into small (about 20 cm by 2.0 cm) pieces (e.g. crude fragments));
loading an isotonic solution into a processing chamber;
adding the minced tissue to the isotonic solution in the processing chamber (About 12 grams of placental membrane and three pieces of ice cubes were mechanically dispersed together for 2 minutes, and three more pieces of ice cubes were added into the mixture and dispersed for another minute)
milling the minced tissue in the processing chamber into the particulated tissue (tissues were mechanically dissociated using a homogenizer); and
collecting the particulated tissue (Then the dispersed soft tissue was transferred onto a sterile sieve and transferred into molds) (Example 7, page 15).
Qin teaches that the temperature of soft tissue may be controlled by adding ice ( e.g., an isotonic solution) to the soft tissue prior to, or during, the dispersing process (paragraph 0041).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of processing placental tissue of Shalini by introducing an isotonic solution as ice during the homogenization step 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 Qin teaches that the dispersing step (i.e. homogenization) can cause temperature increases and using an isotonic solution in ice form can help control the temperature by limiting the temperature increase caused by homogenization (paragraph 0041). As such, it would have been obvious to add the ice to maintain the temperature of the tissue and limit the temperature increase caused by homogenization. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the steps of placing the ice in the processing chamber, then adding the minced tissue (steps c-d of claim 1), the combined teachings of Shalini and Qin are silent as to the order of introducing the iced isotonic solution and the minced tissue to the processing chamber.
It would have been obvious to the ordinary artisan that one could either add the tissue to the chamber first, the ice to the chamber first, or both at the same time as there are a limited number of options. As such, it would have been obvious that the ice could be added to the processing chamber prior to adding the minced tissue.
It would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.). Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the processing chamber, Shalini teaches that they used a handheld homogenizer (page 42, column 1, paragraph 5-column 2, paragraph 1). Shalini does not teach wherein the rotor mill is the processing chamber.
However, Qin teaches using a blender to homogenize tissues (example 7). The blender of Qin is considered to be a processing chamber that is a rotor mill.
It would have been obvious to one of ordinary skill in the art that they could have used the blender of Qin instead of the hand homogenizer of Shalini as both are used for the same purpose of making homogenized particulated tissue. Furthermore, one of ordinary skill in the art would reasonably understand that a blender would provide more consistent homogenization between batches compared to the use of a hand homogenizer as the hand homogenizer has a greater risk of variability in use between batches especially during extended use in processing a multitude of samples. As such, it would have been obvious to use a blender instead of the hand homogenizer of Shalini.
Furthermore, Qin teaches that their method of homogenizing tissue into dispersed soft tissue (i.e. particulated tissue) may comprise sieving the dispersed soft tissue on a sieve with a pore size of about 0.5 mm (or 500 μm) (paragraph 0062 and Example 7). Qin teaches that they dispersed 12 grams of placental tissue by blending for 3 minutes total, then the dispersed tissue was transferred into molds and the undispersed tissue was dispersed for another 2 minutes (Example 7).
The combined teachings of Shalini and Qin do not teach wherein the sieve is part of the rotor mill.
However, it would have been obvious to one of ordinary skill in the art that they could attach a sieve to the top of the blender to ensure only dispersed (i.e. tissue of the appropriate size that fits through the pores) tissue enter the molds and to identify undispersed tissue that requires further dispersion. As the additional dispersion occurs in the same processing chamber (the blender), it would have been obvious to attach a sieve to the top of the blender for removing dispersed tissue while retaining undispersed tissue in the processing chamber for further dispersion. Using a sieve attached to the top of the blender would represent the simplest form for sieving the dispersed tissue as using one separate from the processing chamber would require transferring the tissue to the sieve and transferring the identified undispersed tissue back to the processing chamber for further dispersal. As such, it would have been obvious to choose the simpler process of attaching the sieve to the blender. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 3, Shalini teaches that they collected human placental tissue (page 42, column 1, paragraph 5-column 2, paragraph 1).
Regarding claims 4-5, Shalini is silent regarding the size of the pieces of the minced fetal tissue.
However, Qin teaches that minced (crudely fragmented) tissue can be cut into 0.5 x 0.5 cm pieces (equates to 0.25 cm2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the minced tissue sample pieces of Shalini could be about 0.25 cm2, as identified by Qin, to arrive at the instantly claimed invention. One of ordinary skill in the art would reasonably understand that an isolated placental tissue could be cut into 0.25 cm2 pieces as Qin specifically teaches that minced (crudely fragmented) tissue can be cut into 0.5 x 0.5 cm pieces (equates to 0.25 cm2) before homogenizing the tissue. As such, it would have been obvious to one of ordinary skill in the art that placental tissue could be cut into 0.25 cm2 pieces as this was a known size used within the art. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 7, Qin teaches that the ice can be 1 cm3 (equates to 1 cm2) (paragraph 0044).
Regarding claim 8, Qin, as stated supra, teaches that temperature of soft tissue may be controlled by adding ice ( e.g., an isotonic solution) to the soft tissue prior to the dispersing process (paragraph 0041)
Regarding claim 9, Qin, as stated supra, teaches that their method of homogenizing tissue into dispersed soft tissue (i.e. particulated tissue) may comprise sieving the dispersed soft tissue on a sieve with a pore size of about 0.5 mm (or 500 μm) (paragraph 0062 and Example 7).
Regarding claims 10-11, Shalini teaches that the minced tissue is milled at 9000 rpm. As applicant has provided no definition for “about”, “about 6,000 rpm” is considered to range by an order of magnitude (i.e. 600 to 60,000 rpm) and the 9000 rpm of Shalini falls within these limitations. Hartman evidences that within an order of magnitude has previously been used as a definition for about (column 24, lines 19-24). Therefore, an order of magnitude is considered to fall within the broadest reasonable interpretation of the definition of about.
Furthermore, under an alternative interpretation of about, ±50% is also considered to fall within the broadest reasonable interpretation of about as the lower limit for rpm is about 3,000 rpm and ±50% of 6,000 rpm would be in the 3,000-9,000 rpm range, which is within the lower and upper limit as defined by claim 10. The 9000 rpm of Shalini falls within these limitations.
Regarding claim 14, the combined teachings of Shalini and Qin do not teach wherein the processing chamber is purged with the isotonic solution to collect residual particulated tissue.
However, the concept of quantitative transfer is well understood in the field and it would have been obvious to purge the processing chamber with the isotonic solution as a liquid to collect any residual tissue to ensure no sample is lost when transferring to a new container (i.e. the processing chamber to the molds). Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed September 23, 2025, are acknowledged.
Applicant argues that the cited documents fail to teach or suggest all of the claimed features. Specifically, Applicant argues that the cited art fails to disclose loading frozen isotonic solution into the processing chamber; milling the unfrozen soft tissue with a rotor mill having a sieve with a pore size between about 200 μm and about 1 mm; and milling the minced tissue with frozen isotonic solution after providing both the tissue and frozen isotonic solution to the processing chamber prior to running the rotor mill.
Applicant argues that Shalini fails to teach using a rotor mill as a homogenizer is not a rotor mill and does not use a sieve. Applicant argues that Qin uses a blender, beater, or mixer and these are not rotor mills and Qin does not disclose the use of a sieve. Applicant argues that Qin teaches using ice cubes made from ultrapure water and not isotonic solution. Applicant cites to FDA Elemental Analysis Manual to provide a definition of rotor mill (page 7, paragraph 4-page 10, paragraph 3).
Applicant's arguments and cited prior art 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). The rejection is based on the combined teachings of Shalini and Qin. As such, the individual references are not required to teach all of the claimed limitations on their own. As discussed above, the combined teachings of Qin and Shalini teach all of the elements of the claimed method.
Regarding whether the homogenizer and blender of Shalini and Qin, respectively, are considered to fall within the broadest reasonable interpretation of a “rotor mill”, it is noted that the specification has not provided a special definition for a rotor mill. Although FDA Elemental Analysis Manual and the Applicant identify a specific definition for rotor mill, the claims are not bound to this definition as there is no special definition limiting the rotor mill to this particular definition. Therefore, the art is examined for assessing the broadest reasonable interpretation of the term rotor mill. Lopes evidences that rotor-stator homogenizers can be considered mills and would, thus, also be a rotor mill (page 29, paragraph 4). Furthermore, Noor (page 870, column 1, paragraph 3) and Scanlon (whole document) evidences that blender can also be considered mills. As blenders include a rotor, they are also considered to fall under the broadest reasonable interpretation of a rotor mill. Therefore, the homogenizer of Shalini and the blender (Example 7) of Qin are considered to be rotor mills.
Applicant is welcome to further define the structure of the rotor mill within the claims in such a way as to preclude homogenizers and blenders from the broadest reasonable interpretation of a rotor mill.
Regarding the sieve, Qin specifically identifies that their method of homogenizing tissue into dispersed soft tissue (i.e. particulated tissue) may comprise sieving the dispersed soft tissue on a sieve with a pore size of about 0.5 mm (or 500 μm) (paragraph 0062 and Example 7). Qin teaches that they dispersed 12 grams of placental tissue by blending for 3 minutes total, then the dispersed tissue was transferred into molds and the undispersed tissue was dispersed for another 2 minutes (Example 7). Although the combined teachings of Shalini and Qin do not teach wherein the sieve is part of the rotor mill, it would have been obvious to one of ordinary skill in the art that they could attach a sieve to the top of the blender to ensure only dispersed (i.e. tissue of the appropriate size that fits through the pores) tissue enter the molds and to identify undispersed tissue that requires further dispersion. As the additional dispersion occurs in the same processing chamber (the blender), it would have been obvious to attach a sieve to the top of the blender for removing dispersed tissue while retaining undispersed tissue in the processing chamber for further dispersion. Using a sieve attached to the top of the blender would represent the simplest form for sieving the dispersed tissue as using one separate from the processing chamber would require transferring the tissue to the sieve and transferring the identified undispersed tissue back to the processing chamber for further dispersal. As such, it would have been obvious to choose the simpler process of attaching the sieve to the blender.
Regarding the isotonic solution, Qin specifically teaches that the temperature of soft tissue may be controlled by adding ice made from isotonic solution to the soft tissue prior to, or during, the dispersing process (paragraph 0041). Although ultrapure water is another option considered for the ice, ice cubes made from isotonic solution is also an option. MPEP 2143.01(I) states that the court stated that "the prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." Id. In affirming the Board' s obviousness rejection, the court held that the prior art as a whole suggested the desirability of the combination of shoe sole limitations claimed, thus providing a motivation to combine, which need not be supported by a finding that the prior art suggested that the combination claimed by the applicant was the preferred, or most desirable combination over the other alternatives. Id. See also In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016). Therefore, one of ordinary skill in the art would understand that isotonic solution can be used for making the ice.
Therefore, Applicant’s arguments regarding Shalini and Qin not teaching the identified limitations are considered unpersuasive.
Furthermore, Applicant argues that Examiner’s interpretation of about is inconsistent with the specification. Applicant argues that an order of magnitude is unreasonable as the widest disclosed range for rpm of the rotor mill is about 3,000 rpm to about 18,000 rpm. Applicant argues that an ordinary artisan, when reading the specification, would understand that "about" does not mean a scope of an order of magnitude, but a set of values that is approximately or near the assigned value (page 10, paragraph 4-page 11, paragraph 1).
Applicant's arguments have been fully considered but they are not persuasive.
Regarding the reasonableness of defining about as an order of magnitude, Hartman evidences that within an order of magnitude has previously been used as a definition for about (column 24, lines 19-24). Therefore, an order of magnitude is considered to fall within the broadest reasonable interpretation of the definition of about.
Furthermore, even if one were to limit the definition of about to a value less than an order of magnitude, under an alternative interpretation of about, ±50% is also considered to fall within the broadest reasonable interpretation of about as the lower limit for rpm is about 3,000 rpm and ±50% of 6,000 rpm would be in the 3,000-9,000 rpm range, which is within the lower and upper limit as defined by claim 10. The 9000 rpm of Shalini falls within these limitations.
Applicant argues that adding the frozen isotonic solution prior to adding the minced tissue produces superior cell viability, as shown in Example 2 and Figure 4 (page 12, paragraphs 3-4).
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, Example 2 performs processing in the rotor mill at a speed of 6,000 rpm for 10 seconds. As such, the claims as written are not commensurate in scope with alleged unexpected results. Furthermore, MPEP 716,02(b) discloses that the evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319. As can be seen in Figure 4, the results when preloading the ice exhibit overlapping error bars with loading the ice and tissue together and loading the tissue firs, then ice. Therefore, it is unclear whether loading the ice first actually results in statistically significant increases in cell viability.
Therefore, Applicant’s arguments regarding unexpected results are considered unpersuasive.
Claims 1 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Shalini et al. (Regenerative Research 2: 41-49. 2013) and United States Patent Application No. 20180044629 (Qin), as applied to claim 1 above and further in view of Sander et al. (Journal of Pharmaceutical and Biomedical Analysis 160: 297–300. 2018), and Marquez-Curtis et al. (Cryobiology 71: 181–197. 2015). This rejection is repeated with regards to the rejection in the Final rejection mailed on June 26, 2025. Applicant’s traversal has been addressed above.
The combined teachings of Shalini and Qin are discussed above. Shalini teaches that they homogenized the tissue for 10-15 minutes (page 42, column 1, paragraph 5-column 2, paragraph 1).
The combined teachings of Shalini and Qin do not teach wherein the milling occurs for 10 seconds.
However, Sander teaches that rotor-stator homogenization is performed for 10 seconds with frozen placental tissue (page 298, column 1, paragraph 2).
Regarding the limitation, wherein the minced tissue sample is unfrozen, this is considered to only be associated with the minced tissue sample of step b and not the minced tissue of steps d and e as the terminology used is different between step b (minced tissue sample) and steps d and e (minced tissue).
Although Sander flash-freezes the tissue, they are silent to the MSC being viable upon thawing. However, Marquez-Curtis demonstrates that viable MSC cells can be collected from flash-frozen cryopreserved umbilical tissue after thawing (Section 5, pages 191-192).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of processing placental tissue of the combined teachings of Shalini and Qin with the method of processing frozen placental tissue of Sander and Marquez-Curtis 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 the homogenization step of Sander is only 10 seconds compared to the homogenization of Shalini of 10-15 minutes. Furthermore, Marquez-Curtis demonstrates that flash-frozen cryopreserved tissues can still generate viable MSC cells after thawing. Therefore, it would have been obvious to use the homogenization procedure of Sander because it is significantly shorter. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 1 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Shalini et al. (Regenerative Research 2: 41-49. 2013) and United States Patent Application No. 20180044629 (Qin), as applied to claims 1 and 14 above, and further in view of Marquez-Curtis et al. (Cryobiology 71: 181–197. 2015) and USP (<1044> Cryopreservation of Cells. 2018). This rejection is repeated with regards to the rejection in the Final rejection mailed on June 26, 2025. Applicant’s traversal has been addressed above.
The teachings of Shalini and Qin are as discussed above. Qin teaches that after collecting the particulated tissue in molds, the molds can be cryopreserved (Example 7).
The combined teachings of Shalini and Qin do not teach wherein the processing chamber is purged with an additional isotonic solution.
However, it would have been obvious to cryopreserve the MSCs collected by Shalini for future use as Marquez-Curtis teaches that cryopreserving cells allows one to bank MSCs to increase their access and availability when they are needed (abstract). Furthermore, Marquez-Curtis teaches that tissues can be frozen with MSCs for collection upon thawing and that viable MSC cells can be collected from these cryopreserved tissue (Section 5, pages 191-192).
Furthermore, USP teaches that cryoprotective agents (CPAs) are commonly used during cryogenic freezing of tissues and cells to suppress ice formation, which damage the cell membrane. USP teaches several intracellular CPAs [e.g., dimethylsulfoxide (DMSO), glycerol, propanediol, and methanol] which must be able to cross the cell membrane readily and penetrate the cell without significant toxicity. There also is a group of extracellular CPAs (e.g., sucrose and trehalose) (page 1, paragraph 3). USP teaches that preservation of cells typically requires the use of specialized solutions that contain a base (typically an isotonic saline-based solution) with CPAs (most commonly DMSO but sometimes glycerol) and sometimes proteins (fetal bovine serum, human serum or plasma, conditioned medium, or human albumin) (page 2, paragraph 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of processing frozen placental tissue of the combined teachings of Shalini, Qin, and Marquez-Curtis to include purging the processing chamber with a different isotonic solution to collect residual tissue 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 quantitative transfer is a well known concept, so it would have been obvious to use an isotonic solution to collect residual particulate tissue to ensure that all tissue was collected. Furthermore, Marquez-Curtis teaches that MSCs can be cryopreserved to bank cells for future use to ensure they are accessible and available when needed. As such, a cryoprotectant solution would be needed to ensure ice crystal don’t form in the particulated tissue (containing the MSCs), as identified by USP. It would have been obvious that one could use the cryoprotectant solution containing the base isotonic solution with added CPAs (i.e. a different isotonic solution) for quantitative transfer of the residual tissue particulates in the processing chamber to allow for more immediate freezing of the tissue-solution. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Conclusion
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/KEENAN A BATES/Examiner, Art Unit 1631