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 .
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2 (a), (b) and (h), 10, 40, 43-47 are rejected under 35 U.S.C. 103 as being obvious over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam, et al. "Human serum is an advantageous supplement for human dermal fibroblast expansion: clinical implications for tissue engineering of skin." Archives of medical research 39.8 (2008): 743-752.
The applied reference has a common inventor, Pete O’Heeron with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, O’ Heeron teaches producing a plurality of fibroblast organoids (paragraph 0010, page 1). O’Heeron also teaches culturing foreskin fibroblasts by suspending them in DMEM with low-glucose ( paragraph 0059, page 12), 0% non-essential amino acids, 0% L-glutamine, 10% fetal bovine serum (FBS) and in one embodiment, the bioprinting of fibroblast organoids in placental extracellular matrix in the presence of various tackifiers such as fibronectin, laminin and collagen (paragraph 0040, page 7). The limitations ‘for storage and/or transportation are intended uses of the claimed method and not given patentable weight.
O’Heeron does not teach the use of human serum (HS).
Mazlyzam teaches the culturing fibroblasts with 10% human serum, showing the advantages of using HS over FBS. Mazlyzam teaches that HS works better in generating larger numbers of cells in a short period of time, influencing the mRNA expression of type III collagen and fibronectin which are important extracellular matrix proteins that sustain fibroblast cultures (abstract, page 743).
Regarding claim 2 (a), (b) and (h), (a) Mazlyzam teaches suspending fibroblasts in 0-10 % HS (abstract, page 743),(b) Mazlyzam teaches culturing fibroblasts in 10% HS (abstract, page 743) , (h) O’Heeron teaches suspending fibroblasts in media containing the tackifier, 4% type I collagen (paragraph 0040, page 7).
Regarding claim 10, O’Heeron teaches the bioprinting of fibroblast organoids in placental extracellular matrix in the presence of various tackifiers such as collagen (paragraph 0040, page 7)
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches a method of producing fibroblast organoids and modify it with Mazlyzam that teaches the replacement of FBS with HS. One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron and Mazlyzam to improve the efficiency of fibroblast organoid production. There’s reasonable expectation of success to combine the teachings of O’Heeron and Mazlyzam, because O’Heeron teaches production of plurality of fibroblast organoids in the suspension media discussed above, and Mazlyzam teaches the advantage of replacing FBS with HS to improve fibroblast culture efficiency.
Regarding claim 40, the claim recites the dissociation of fibroblasts from the organoids, upon being exposed to at least one protease. “Upon being exposed to at least one protease” is a conditional limitation, which is not given patentable weight. It appears that fibroblasts are capable of being released from the organoids taught by the combination of O’Heeron and Mazlyzam.
Claims 43-47, have intended use limitations which are not given patentable weight.
Regarding claim 43, 44 and 45, these claims recite the intended use limitation of using fibroblast organoids within 0-21 days, 1-5 day, and 3 days of the suspending step respectively. Since these are intended use limitations, they are not given patentable weight. It appears that the fibroblast organoids taught by the combination of O’Heeron and Mazlyzam are capable of being used within 0-21 , 1-5 or 3 days of suspending step.
Regarding claim 46, this claim recites the intended use of fibroblast organoids as an alternative to an animal model. Since it is an intended use limitations it is not given patentable weight. It appears that the fibroblast organoids taught by the combination of O’Heeron and Mazlyzam are capable of being used as an alternative to an animal model.
Regarding claim 47, this claim recites the intended use of fibroblast organoids in pre-clinical drug testing or drug development, for using the fibroblast organoids to study organ function and/or to satisfy requirements for drug screening. Since these are intended use limitations, they are not given patentable weight. It appears that the fibroblast organoids taught by the combination of O’Heeron and Mazlyzam are capable of being used in any of the assays recited in the claim.
Claim 2 (c)-(f), 11, 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam et al. as applied to claims 1,2 and 10 above, and further in view of Furukawa, et al. "Formation of human fibroblast aggregates (spheroids) by rotational culture." Cell Transplantation 10.4-5 (2001): 441-445, and Salmenperä, et al. "Formation and activation of fibroblast spheroids depend on fibronectin–integrin interaction." Experimental cell research 314.19 (2008): 3444-3452.
The teachings of O’ Heeron and Mazlyzamare relied on above.
O’Heeron and Mazlyzam do not teach fibroblast organoid storage media containing non-essential amino acids and L-glutamine, the size of the fibroblast organoids, hanging drop method of producing the organoids, the number of cells per organoids, culture duration of organoids and the maintenance of humidity of the culture chamber.
Regarding claim 11 (a) and (b), (a) Furukawa teaches producing fibroblast spheroids with diameters ranging from 50-500 µm (Figure 2, page 443), (b) and also, producing fibroblast spheroids with diameter about 250 µm at 25hrs. in culture (Figure 2, page 443).
Furukawa does not teach the fibroblast organoid storage media containing non-essential amino acids and L-glutamine, hanging drop method of producing the organoids, the number of cells per organoids, and the maintenance of humidity of the culture chamber.
Regarding 2 (c)-(f) Salmenpera teaches growing fibroblast organoids in growth medium containing non-essential amino acids and L-glutamine (i.e, DMEM/F12), as evidenced by https://www.thermofisher.com/us/en/home/technical-resources/media-formulation.55.html
One of ordinary skill in the art would have recognized that routine optimization would render the recited concentrations of the non-essential amino acids and L-glutamine obvious.
Please see MPEP 2144.05 (II) Routine optimization.
Regarding 11 (c) Salmenperä teaches; plating fibroblasts on U-bottom, agarose-pretreated culture plates, agarose is known in the art to provide low-attachment surface (step 1), and the hanging drop method of culturing to exclude the effect of agarose on fibroblast activation (step 2-4) (cell culture, page 3445).
The steps 3-4 are not disclosed in the mentioned prior art as explicitly same as the instant application. However, the limitations in claim 11 (c), steps 1-4 are interpreted as product by process type limitations. If the claimed product is the same or obvious from a product in the prior art (i.e. the product disclosed in the cited reference), the claim is unpatentable even though the reference product was made by a different process. When the prior art discloses a product which reasonably appears to be identical with or slightly different than the claimed product-by-process, rejections under 35 U.S.C 102 and/or 35 U.S.C 103 are proper. (MPEP 2113)
Furthermore, it is noted that the method for producing the fibroblast organoids is immaterial or inconsequential to the operation of the method. In other words, fibroblast organoids in Furukawa and Salmenperä appear to be structurally same as the claimed organoids regardless of method of production, absent a showing of secondary considerations.
Regarding claim 11 (d) Salmenperä teaches starting fibroblast spheroid cultures with 5X104 number of cells indicating the spheroids contain 104 or more number of cells as the method successfully produced spheroids with multiplicity of initial number of cells (cell culture, page 3445).
Regarding claim 11(e), Salmenperä teaches producing fibroblast spheroids at 37oC for about 24-48 or more, illustrating the localization of fibronectin in untreated spheroids at 24 hrs. (fig.1 , page 3447), in 5% CO2, and the method used a dish containing phosphate-buffered saline to create extra humidity (cell culture, page 3445). It’s well known in the art to culture cells in humidity greater than 80%, as evidenced by Klein et al., which teaches incubation of mammalian cells in incubators with humidity of ~ 90% to facilitate the growth of various mammalian cell lines, in their efforts streamline the cell culture process and enhance reproducibility (abstract, page 1, methods, page 7). Therefore, it is obvious for a person of ordinary skill in the art to assume that the humidity of the culture chamber/incubator was maintained at or above 80% (also, 11 (l) and (m)).
Regarding claim 11(f), Salmenperä teaches producing fibroblast spheroids upon culturing for 24- 48hrs. or more (fig.1 , page 3447).
Regarding claim 11(g), Salmenperä teaches producing fibroblast spheroids upon culturing for 24 hrs. or more (fig.1 , page 3447).
Regarding claim 11(h), Salmenperä teaches producing fibroblast spheroids at 37 oC which is in the range of 35-37 oC (cell culture, page 3445) .
Regarding claim 11(i), Salmenperä teaches producing fibroblast spheroids at 37 oC (cell culture, page 3445).
Regarding claim 11(j), Salmenperä teaches producing fibroblast spheroids in 5% CO2 which is in the range of 4- 5% CO2.
Regarding claim 11(k), Salmenperä teaches producing fibroblast spheroids in 5% CO2.
Regarding claim11 (l) and (m) Salmenperä used a dish containing phosphate-buffered saline to create extra humidity (cell culture, page 3445). It’s well known in the art to culture cells in humidity greater than 80%, as evidenced by Klein et al. which teaches incubation of mammalian cells in incubators with humidity of ~ 90% to facilitate the growth of various mammalian cell lines, in their efforts streamline the cell culture process and enhance reproducibility (abstract, page 1, methods, page 7). Therefore, it’s obvious to culture fibroblast organoids at 85-90% humidity or at 90%.
Regarding claims 24 and 25 Furukawa teaches the size, or the diameter of the fibroblast spheroids are dependent on the duration of the time of production (Figure 2, page 443).
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches a method of producing fibroblast organoids, and modify it with Mazlyzam that teaches the replacement of FBS with HS; and further modify it with the teachings of Furukawa that teaches the diameter of fibroblast organoids which changes with the duration of time in culture, and Salmenperä that teaches the hanging drop culture method, the number of cells per organoids, culture duration and the maintenance of humidity of the culture chamber. One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron and Mazlyzam with Furukawa and Salmenperä to improve the efficiency of fibroblast organoid production. There’s reasonable expectation of success to combine the teachings of O’Heeron , Mazlyzam , Furukawa and Salmenperä because, Furukawa and Salmepera illustrate the production of plurality of fibroblast organoids with their respective methods.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam et al. as applied to claims 1,2 and 10 above, and further in view of Kunz-Schughart, et al., "Adaptation of an automated selective dissociation procedure to two novel spheroid types." In vitro cellular & developmental biology. Animal (1997): 73-76.
The teachings of O’ Heeron and Mazlyzam are relied above.
O’Heeron and Mazlyzam do not teach dissociation of fibroblasts from fibroblast organoids with exposure to at least one protease.
Regarding claim 40, Kunz-Schughart teaches dissociation of spheroid derived from tumorigenic Rat1-T1 cells originated from embryo fibroblasts, upon exposure to various cocktails of proteases which comprises of at least one or more proteases (Table 1, page 74).
Also, regarding claim 40 please see claim interpretation and 112b rejection sections above.
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches a method of producing fibroblast organoids , and modify it with Mazlyzam that teaches the replacement of FBS with HS; and further modify it with the teachings of Kunz-Schughart that teaches the dissociation of cells of fibroblast origin ( Rat1-T1) from their spheroid/organoid structure when exposed to at least one protease . One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron and Mazlyzam with Kunz-Schughart to successfully dissociate fibroblasts from their spheroid/organoid structure. There’s reasonable expectation of success to combine the teachings of O’Heeron , Mazlyzam , and Kunz-Schughart. Because Kunz-Schughart illustrate the dissociation of cells with fibroblast origin with various cocktails of proteases that contain at least one protease.
Claim 43-45, 52, 61-62, 64, 66-67 are rejected under 35 U.S.C. 103 as being unpatentable over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam et al. as applied to claims 1-3 above, and further in view Noguchi, Ryo, et al. "Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease." The Journal of Heart and Lung Transplantation 35.1 (2016): 137-145.
The teachings of O’ Heeron et al. (US2021/0254013 A1) and Mazlyzam et al. are relied above.
O’Heeron and Mazlyzam do not teach the use of fibroblast organoids within 0-21 days, for one or more assays, administering the organoids to an individual at a therapeutically effective dose, dissociation of fibroblasts from the organoids, migration of the dissociated fibroblasts specific tissue and organ.
Regarding claim 43, Noguchi teaches the use of contractile cardiac spheroids generated from rat neonatal ventricular cardiomyocytes, human dermal fibroblasts and human coronary microartery endothelial cells within 3 days of 3D culture to study their mechanical properties and transplantation into nude mice ( fig, 1, and experimental protocol, page 138).
Regarding claim 44, Noguchi teaches the use of contractile cardiac spheroids containing human dermal fibroblasts within 1-3 days of 3D culture which is in the range of 0-5 days, to study their mechanical properties and transplantation into nude mice ( fig, 1, and experimental protocol, page 138).
Regarding claim 45, Noguchi teaches the use of contractile cardiac spheroids generated from rat neonatal ventricular cardiomyocytes, human dermal fibroblasts and human coronary microartery endothelial cells within 3 days of 3D culture to study their mechanical properties and transplantation into nude mice ( fig, 1, and experimental protocol, page 138), in order to advance their efforts on regenerating damaged cardiac tissue.
Regarding claim 52, Noguchi teaches administering/grafting cardiac spheroids containing fibroblasts into F344 nude rats in their efforts to develop cardiac tissue capable of being grafted into damaged native hearts (background, page 137), at a therapeutically effective amount to cause synchronous beating of the cardiac patch which was confirmed electro physiologically and mechanically (background, page 137).
Regarding claim 61, Noguchi teaches administering cardiac spheroids containing fibroblasts into F344 nude rats (background, page 137). Noguchi also teaches that poor retention of cardiac/fibroblast spheroids after administration as a potential limitation of this grafting method (page 143, paragraph1). Therefore, fibroblast dissociation from the organoids must be inherent to the art. Also, endogenous proteases are inherently present in tissues which may cause the dissociation of fibroblasts from their organoid structure as recited in claim 40.
Claim 61 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since these claims only recite the results of the steps, then art reading on claim 61 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Regarding claim 62, Noguchi teaches administering cardiac spheroids containing fibroblasts into F344 nude rats (background, page 137) and poor retention of cardiac/fibroblast spheroids after administration as a potential limitation of this grafting method (page 143, paragraph1) which reads on fibroblast release/extended release from organoids.
Also, endogenous proteases are inherently present in tissues which may cause the dissociation of fibroblasts over time, from their organoid structure as recited in claim 40 (see claim interpretation for ‘extended release’).
Claim 62 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since these claims only recite the results of the steps, then art reading on claim 62 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Regarding claim 64, 66 and 67, Noguchi teaches administering cardiac spheroids containing fibroblasts into F344 nude rats’ heart (background, page 137) and poor retention of cardiac/fibroblast spheroids after administration as a potential limitation of this grafting method (page 143, paragraph1). Since the organoid is administered to the heart, the dissociated fibroblasts will be in the heart muscle and migrate in the heart, as in the connective tissue (claims 64 and 67) and also nervous tissue that in the heart (claim 66).
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches a method of producing fibroblast organoids, and modify it with Mazlyzam that teaches the replacement of FBS with HS; and further modify it with the teachings of Noguchi that teaches the use of cardiac/fibroblast organoids within 1-3 days of 3D culture, for one or more assays, administering the organoids to F344 nude rats at a therapeutically effective dose and dissociation of fibroblasts from the organoids. One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron and Mazlyzam with Noguchi to successfully generate fibroblast organoids that can be administered to a subject at a therapeutically effective dose. There’s reasonable expectation of success to combine the teachings of O’Heeron , Mazlyzam, and Noguchi. Because O’Heeron , Mazlyzam illustrates methods to improve fibroblast organoid cultures, and Noguchi illustrate the administration of cardiac/fibroblast organoids into mice with success.
Claim 71 rejected under 35 U.S.C. 103 as being unpatentable over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam et al. as applied to claims 1,2 and 10 above, and further in view Noguchi, Ryo, et al. "Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease." The Journal of Heart and Lung Transplantation 35.1 (2016): 137-145., and Ahangar, Parinaz, et al. "Human gingival fibroblast secretome accelerates wound healing through anti-inflammatory and pro-angiogenic mechanisms." NPJ Regenerative medicine 5.1 (2020): 24.
The teachings of O’ Heeron, Mazlyzam, and Noguchi are relied above.
O’Heeron, Mazlyzam and Noguchi do not teach the release of one or more therapeutic agents from fibroblasts.
Regarding claim 71, Ahanga teaches the release of anti-inflammatory and proangiogenic factors from human gingival fibroblasts (abstract, page 1). Analysis of fibroblast secretome revealed the release of factors such as VEGF, FGF-2 which promotes angiogenesis and wound healing (analysis of hGF secretome, paragraph 1, page 4).
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches producing a plurality of fibroblast organoids by suspending the cells in a storage matrix containing low-glucose ( paragraph 0059, page 12), 0% non-essential amino acids, 0% L-glutamine, 10% fetal bovine serum (FBS), and tackifier, and modify it with Mazlyzam that teaches the replacement of FBS with HS. And further modify it with the teachings of Noguchi that teaches the use of cardiac/fibroblast organoids within 1-3 days of 3D culture, for one or more assays as an alternative to an animal model, administering the organoids to F344 nude rats at a therapeutically effective dose and dissociation of fibroblasts from the organoids, and Ahanga that teaches the release of one or more therapeutic agents such as VEGF, and FGF-2 from fibroblasts. One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron, Mazlyzam, Noguchi and Ahanga to successfully generate fibroblast organoids that can be administered to a subject such that they can release therapeutic agents (as noted above) from fibroblasts. There’s reasonable expectation of success to combine the teachings of O’Heeron, Mazlyzam, Noguchi, and Ahanga. Because O’Heeron , Mazlyzam, and Noguchi illustrate methods to improve fibroblast organoid cultures, and the administration of cardiac/fibroblast organoids into mice respectively, and Ahanga teaches the release of therapeutic agents from fibroblasts such as VEGF, and FGF-2.
Claims 46, 47, 50 are rejected under 35 U.S.C. 103 as being unpatentable over O’ Heeron et al. (US2021/0254013 A1) in view of Mazlyzam et al. as applied to claims 1,2 and 10 above, and further in view of Skardal, et al., "Drug compound screening in single and integrated multi-organoid body-on-a-chip systems." Biofabrication 12.2 (2020): 025017.
The teachings of O’ Heeron and Mazlyzam are relied above.
O’Heeron, and Mazlyzam do not teach the use of fibroblast organoids as an alternative to animal models, pre-clinical drug testing or drug development, exposing the organoids to one or more drugs.
Regarding claim 46, Skardal teaches the use of cardiac organoids constructed using fibroblasts and iPSC derived cardiomyocytes (Materials and methods, 2.1 Liver and cardiac cell sources, culture, and organoid formation, page 3) and the organoids were used to screen the cardiac toxicity of FDA-recalled drugs including rofecoxib and terodiline (fig. 2, page 8). Their effort was to develop 3D organoid models to eliminate the use of animal models in drug screening, because animal models used for pre-clinical drug screening have major limitations as they can be expensive, difficult to maintain and often fail to accurately model human metabolism, drug efficacy and immune function ( Introduction, paragraph 2, page2).
Regarding claim 47, Skardal teaches the use of cardiac/fibroblast organoids model generated with fibroblasts and other cells (Materials and methods, 2.1 Liver and cardiac cell sources, culture, and organoid formation, page 3) in pre-clinical drug studies ( Introduction, paragraph 2, page2) and validated the model with the heartbeat assay (page 4) and drug studies (Figure 2, page 8) to satisfy the requirements for drug screening capabilities.
Regarding claim 50, Skardal teaches exposing the cardiac /fibroblast organoids to one or more drugs such as, FDA-recalled drugs including rofecoxib, terodiline (fig. 2, page 8), as well as over-the -counter NSAIDS (fig.4, page 11) in order to study the organ toxicity of said drugs.
Therefore, it will be obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to utilize the above-mentioned teaching of O’Heeron that teaches a method of producing fibroblast organoids and modify it with Mazlyzam that teaches the replacement of FBS with HS. And further modify it with the teachings of Skardal that teaches use of fibroblast organoids as an alternative to animal models, pre-clinical drug testing or drug development, use of organoids to satisfy the requirements for drug screening and exposing the organoids to one or more drugs. One of ordinary skill in the art would have been motivated to combine the teachings of O’Heeron, Mazlyzam, and Skardal to use the generated to fibroblast organoids in pre-clinical drug testing as an alternative to animal models. s There’s reasonable expectation of success to combine the teachings of O’Heeron , Mazlyzam, and Skardal. Because O’Heeron , Mazlyzam, illustrate methods to improve fibroblast organoid cultures, and Skardel teaches the successful use of cardiac/fibroblast organoids to screen for drug toxicity.
Therefore, the invention as a whole is a prima facie obvious.
Response to Arguments
Applicant’s arguments filed on 05/26/2026 have been fully considered but they are not persuasive.
A new 35 USC § 103 rejection was made on claim 2 in response to amendments.
The new claims 82-85 are drawn to the non-elected invention made without traverse, on 01/30/2026, over the phone, they are not under examination.
Applicant argues that Office Action does not appear to have given any patentable weight to the term 'storage' in recited ‘storage matrix’, and refers to specification paragraphs 0012, 0014 and 0015 referring to the disclosures regarding the said storage matrix such as; ‘high density and large-scale storage and transportation of cells’, ‘to reduce the shear stress damage inherent in cell use and transport’, and to ‘have a clinically beneficial survival rate with complete biological function after at least seven days of storage under ambient conditions’. The office emphasizes that the applicant is reading specification into the claims, and those disclosures are not requisite limitations in the examined claims. Therefore, the offices’ broadest reasonable interpretation of ‘storage matrix, as the media in which organoids are suspended in’ is maintained.
Applicant argues that in 35 USC 103 rejection over claims 1, 2, and 10, stating that “all words in a claim must be considered in judging the patentability of that claim against the prior art”, referring to MPEP2143.03. Office emphasizes that all the words in the claims were considered in the rejection. The ‘storage matrix’ was evaluated strictly based on the recited limitations that further limited its composition such as, low-glucose media, 0 to20% human serum, etc. O’Heeren teaches producing plurality of fibroblast organoids (paragraph 0010, page 1)and also teaches culturing foreskin fibroblasts by suspending them in DMEM with low-glucose (paragraph 0059) which is in addition to hepatocytes. Therefore, O’Heeron in view of Mazlyzam taught the composition of the ‘storage matrix’, rendering the claim 1 obvious over the stated prior art. The 35 USC 103 rejection over claims 1 and 10 is maintained.
Conclusion
No claim is allowed.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/ Examiner, Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632
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