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 .
Claims 1-17 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-9, in the reply filed on 7-29-26 is acknowledged. The traversal is on the ground(s) that the inventive concept is not a “vascularized respiratory organoid”, but rather combining a blood vessel organoid and respiratory organoid, gelating them, and fusing them such that blood vessel organoid maturation occurs. This is not found persuasive because claim 10 encompasses any “vascularized respiratory organoid” – it does not require it is “matured”. Claim 10 is a product by process and encompasses any “vascularized respiratory organoid” made by other means that has the same structure/function. Claim 10 does not have any structures or functions that distinguish it from any other “vascularized respiratory organoid” made by other means including those described by Dorrello (2017).
Applicants point out Dorrello combined pulmonary epithelial cells while leaving native pulmonary vasculature and supporting lung scaffold intact followed by introducing new cells. Applicants contrast this with applicants method which requires fusing a blood vessel organoid with a lung organoid via gelation. Applicants’ argument is not persuasive because the product of Dorrello is still a “vascularized respiratory organoid” as required in claim 10. Applicants point to features in claims 12-15 that further define the “vascularized respiratory organoid” obtained by applicants. Applicants’ argument is not persuasive because claim 10 is not so limited. Furthermore, there is nothing of record to indicate the features in claim 12-15 are exclusive to the method described by applicants.
If this is not a 371, then the inventions are patentably distinct because the “vascularized respiratory organoid” can be made using another materially different process.
The requirement is still deemed proper and is therefore made FINAL.
Specification
The citations on pg 2 “[Related art document]” and [Patent Document] are missing from the specification.
The specification is missing citations about well-known respiratory organoids in claim 1, specifically those described in the Examples.
The specification is missing citations about well-known blood vessel organoids in claim 1, specifically those described in the Examples.
Claim objections
Please use a) and b) to indicate the steps of claim 1 for clarity and simplicity.
Step b) is actually two steps which should be separated – unless the “culturing” is implicit from the “gelating” (which may just be culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel), in which case the “culturing” is redundant and should be deleted.
It is unclear how the “fusing” in step b) is different than the “gelating” in step a) because the “gelating” may just be culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel. If so, the “fusing” is redundant and should be deleted. If it is an active step, then it is unclear how to “fuse” a blood vessel organoid and a vascularized respiratory organoid. If it is a passive step that is a result of culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel, then the structures/functions of a “fused” “mature” “blood vessel organoid”
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification lacks written description for producing a vascularized respiratory organoid as required in claim 1.
Claim 1 is drawn to a) gelating a blood vessel organoid and respiratory organoid
dispensed into one well; and b) culturing and fusing the gelated blood vessel organoid and respiratory organoid of (a) in a medium for blood vessel organoid maturation.
The metes and bounds of a “blood vessel organoid” in claim 1 cannot be determined. It is unclear if the phrase encompasses a blood vessel sample or fragment. It is unclear whether a blood vessel organoid must be in culture or if it encompasses in vivo embodiments like blood vessel tissue that has been transplanted. It appears to encompass culture-related blood vessel tissue culture, but it is unclear when amalgamation of cells constitute a blood vessel organoid. Blood vessels are primarily made up of endothelial cells, smooth muscle cells, and connective tissue cells. It is unclear whether one of these cell types alone in a cluster constitutes a “blood vessel organoid” or whether two or more of these cells types are required. It is unclear whether any configuration of one or more of these cells types is encompassed by the phrase or whether distinct layers or structures are required. It is unclear whether any non-functional configuration is encompassed by the phrase or whether one or more specific functions are required to be considered a “blood vessel organoid”. The specification and the art at the time of filing do not define the phrase. Therefore, those of skill would not be able to determine the metes and bounds of the phrase.
The metes and bounds of a respiratory organoid in claim 1 cannot be determined. It is unclear if the phrase encompasses any lung, nasal, or mouth tissue sample or fragment. It is unclear whether a “respiratory organoid” must be in culture or if it encompasses in vivo embodiments like respiratory tissue that has been transplanted. It appears to encompass culture-related respiratory tissue culture, but it is unclear when amalgamation of cells constitute a respiratory organoid. Respiratory tissue includes any lung, alveolar, trachea, nasal, or mouth tissue. Lung tissue is primarily made up of epithelial, goblet, basal, club, alveolar type I or II, and endothelial, as well as fibroblasts, immune cells, e.g. macrophages and neutrophils, and connective tissue cells. It is unclear whether one of these cell types alone in a cluster constitutes a “respiratory organoid” or whether two or more of these cells types are required. It is unclear whether any configuration of one or more of these cells types is encompassed by the phrase or whether distinct layers or structures are required. It is unclear whether any non-functional configuration is encompassed by the phrase or whether one or more specific functions are required to be considered a “respiratory organoid”. The specification and the art at the time of filing do not define the phrase. Therefore, those of skill would not be able to determine the metes and bounds of the phrase.
The metes and bounds of “gelating” blood vessel and respiratory tissue in claim 1 cannot be determined. The specification uses the term throughout (pg 6, description of Fig. 4; pg 29, line 9) which appears to be limited to culturing cells on Matrigel (pg 29, lines 6-10). It is unclear what other embodiments are encompassed by “gelating”. The specification uses the phrase “3D culturing” (pg 8, line 17), but all culture methods are in 3 dimensions. The specification does not contemplate using any other well-known hydrogels, e.g. collagen, fibrin, gelatin, PEG, polyacrylamide. Therefore, it is unclear what reagents and active steps are essential to accomplish “gelating” as required in claim 1.
The metes and bounds of “fusing” a blood vessel organoid and a vascularized respiratory organoid in claim 1 are unclear. It is unclear how the “fusing” in step b) is different than the “gelating” in step a) because the “gelating” may just be culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel. If so, the “fusing” is redundant and should be deleted. If it is an active step, then it is unclear what reagents and active steps are essential to accomplish the “fusing”. If it is a passive step that is simply a result of culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel, then the structures/functions of a “fused” “mature” “blood vessel organoid”. Regardless of whether the “fusing” is active or passive, it is unclear when “fusing” occurs because the structures and functions associated with a “fused” blood vessel and vascularized respiratory organoid are not disclosed. Nor are the structures and functions associated with a “mature” blood vessel organoid disclosed.
Example 1, pg 26-27, describes making blood vessel organoids from iPS cells using a STEMdiffTM blood kit and replacing medium through five steps according to the manufacturer’s protocol in Fig. 1 (pg 27, lines 1-12). Figure 1 is so blurry that the medium, reagents, and active steps cannot be discerned.
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There is no way to distinguish how applicants altered the manufacturer’s protocol to arrive at the blood vessel organoids. The structures/functions that define the blood vessel organoids are not disclosed in the specification, the manufacturer’s protocol, or the art at the time of filing. Pg 27, lines 15-25, discuss characteristics of blood vessel organoids and simply say the tissue expressed CD31 and SMA (Fig. 3). It is unclear whether any tissue culture that expresses CD31 and SMA is encompassed by the phrase “blood vessel organoid” or if specific functions are also required. The specification fails to adequately describe how the manufacture’s protocol was modified, and if this is essential to the invention, then the specification lacks written description. Even if the inventive concept encompasses making blood vessel organoids using the manufacturer’s protocol, the specification and the art fail to teach when a “blood vessel organoid” has been obtained.
Example 2, pg 28-30, describes making alveolar organoids from alveolar tissue and airway organoids using basal cells. The structures/functions that define the alveolar or airway organoids are not disclosed in the specification. The specification does not teach structural or functional characteristics of alveolar or airway organoids. The specification does not correlate alveolar or “airway” organoids to non-alveolar lung tissue, nasal tissue, larynx tissue, or mouth tissue. It is unclear whether any alveolar or airway tissue culture is encompassed by the phrase “respiratory organoid” or if specific functions are also required. The structures that define “respiratory organoid”, “alveolar organoid” or “airway organoid” are not disclosed.
Example 3 (pg 30-34) teaches “fusing” vascularized alveolar or airway organoids with “blood vessel organoids”. Example 3-1 (pg 30-32) describes “fusing” “blood vessel organoids” and alveolar organoids such that “vascularized alveolar organoids” are obtained.
Specifically, blood vessel organoids were “transferred to a new EP tube”, alveolar organoids were separated from Matrigel, and transferred to the new EP tube and cultured in Matrigel (pg 31, lines 14-19). The combination of alveolar and blood vessel organoids in matrigel was transferred to “STEMdiffTM blood vessel organoid maturation medium (pg 31, lines 20-22). The specification says a “certain amount of time is required for fusion depending on the distance between organoids or the size of the organoids”, but they were cultured for 2-7 days “to allow the blood vessel organoids and alveolar organoids to fuse” (sentence bridging pg 31-32). The “fusion process can be observed when the distance between blood vessel organoids and alveolar organoids becomes closer” (pg 32, lines 1-2); however, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel organoids and alveolar organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “alveolar organoid” are not disclosed.
Example 3-2 (pg 32) describes placing blood vessel organoids into a “low cell attachment plate, separating airway organoids from Matrigel, and transferring them to the plate (pg 32, lines 8-14). The combination of airway and blood vessel organoids was transferred to “STEMdiffTM blood vessel organoid maturation medium” (pg 32, line 15). Medium was removed and matrigel was added (pg 32, lines 17-19). The specification says a “certain amount of time is required for fusion depending on the distance between organoids or the size of the organoids”, but they were cultured for 2-7 days “to allow the blood vessel organoids and alveolar organoids to fuse” (sentence bridging pg 31-32). “STEMdiffTM blood vessel organoid maturation medium” was added “until fusion could be observed under an optical microscope” (pg 32, lines 19-21). However, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel organoids and airway organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “airway organoid” are not disclosed.
Example 3-3 (pg 32, line 25) analyzes the “fused” organoids. Expression of CD31 and SMA was observed (pg 33, lines 3-5). The organoids “underwent gelation after the maturation stage, resulting in the creation of new blood vessels in the organoids and extending out (Fig. 4A and 4B)” under microscopic observation. However, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel and airway or alveolar organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “airway or alveolar organoid” are not disclosed.
The specification does not teach any non-airway, non-alveolar respiratory organoids fused with blood vessel organoids as broadly encompassed by claim 1.
An adequate written description of making “vascularized” or “mature” “respiratory organoids” by “gelating” blood vessel and respiratory “organoids” and culturing them requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the metes and bounds of blood vessel and respiratory “organoids”, “gelating”, and when the vascularized respiratory “organoids” or “mature” respiratory “organoids” have been obtained. It is not sufficient to define the method solely by its principal biological property, i.e. combining blood vessel and respiratory tissue in culture, because disclosure of no more than that, as in the instant case, is simply a wish to know the metes and bounds of blood vessel and respiratory “organoids”, “gelating”, and when the vascularized respiratory “organoids” or “mature” respiratory “organoids” have been obtained. Also, using jargon to describe blood vessel and respiratory tissue known to exist in the absence of the metes and bounds of blood vessel and respiratory “organoids”, “gelating”, “vascularized respiratory organoids” or “mature respiratory organoids” is not a description of the materials used in claim 1 or the active steps required to perform the method of claim 1. Thus, claiming a method of “gelating” blood vessel and respiratory “organoids” such that “vascularized respiratory organoids” or “mature respiratory organoids” are obtained without defining reagents or means required to do so is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived.
The specification lacks written description for iPS cells derived from alveolar epithelial cells or basal cells as required in claim 3. The specification and the art at the time of filing do not teach any such iPS cells. Therefore, it is not realistic that applicants were in possession of alveolar epithelial cell-derived iPS cells or basal cell-derived iPS cells recited in claim 3.
Enablement
Claims 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for co-culturing mammalian respiratory tissue and blood vessel tissue, does not reasonably provide enablement for the method of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The specification does not enable producing a vascularized respiratory organoid as required in claim 1.
Claim 1 is recited above.
The metes and bounds of a “blood vessel organoid” in claim 1 cannot be determined for reasons recited above.
The metes and bounds of a respiratory organoid in claim 1 cannot be determined for reasons recited above.
The metes and bounds of “gelating” blood vessel and respiratory tissue in claim 1 cannot be determined for reasons recited above.
The metes and bounds of “fusing” a blood vessel organoid and a vascularized respiratory organoid in claim 1 are unclear for reasons cited above.
Example 1, pg 26-27, describes making blood vessel organoids from iPS cells using a STEMdiffTM blood kit and replacing medium through five steps according to the manufacturer’s protocol in Fig. 1 (pg 27, lines 1-12). Figure 1 is so blurry that the medium, reagents, and active steps cannot be discerned (see above). There is no way to distinguish how applicants altered the manufacturer’s protocol to arrive at the blood vessel organoids. The structures/functions that define the blood vessel organoids are not disclosed in the specification, the manufacturer’s protocol, or the art at the time of filing. Pg 27, lines 15-25, discuss characteristics of blood vessel organoids and simply say the tissue expressed CD31 and SMA (Fig. 3). It is unclear whether any tissue culture that expresses CD31 and SMA is encompassed by the phrase “blood vessel organoid” or if specific functions are also required. The specification fails to adequately describe how the manufacture’s protocol was modified, and if this is essential to the invention, then the specification is not enabling. Even if the inventive concept encompasses making blood vessel organoids using the manufacturer’s protocol, the specification and the art fail to teach when a “blood vessel organoid” has been obtained.
Example 2, pg 28-30, describes making alveolar organoids from alveolar tissue and airway organoids using basal cells. The structures/functions that define the alveolar or airway organoids are not disclosed in the specification. The specification does not teach structural or functional characteristics of alveolar or airway organoids. The specification does not correlate alveolar or “airway” organoids to non-alveolar lung tissue, nasal tissue, larynx tissue, or mouth tissue. It is unclear whether any alveolar or airway tissue culture is encompassed by the phrase “respiratory organoid” or if specific functions are also required. The structures that define “respiratory organoid”, “alveolar organoid” or “airway organoid” are not disclosed.
Example 3 (pg 30-34) teaches “fusing” vascularized alveolar or airway organoids with “blood vessel organoids”. Example 3-1 (pg 30-32) describes “fusing” “blood vessel organoids” and alveolar organoids such that “vascularized alveolar organoids” are obtained.
Specifically, blood vessel organoids were “transferred to a new EP tube”, alveolar organoids were separated from Matrigel, and transferred to the new EP tube and cultured in Matrigel (pg 31, lines 14-19). The combination of alveolar and blood vessel organoids in matrigel was transferred to “STEMdiffTM blood vessel organoid maturation medium (pg 31, lines 20-22). The specification says a “certain amount of time is required for fusion depending on the distance between organoids or the size of the organoids”, but they were cultured for 2-7 days “to allow the blood vessel organoids and alveolar organoids to fuse” (sentence bridging pg 31-32). The “fusion process can be observed when the distance between blood vessel organoids and alveolar organoids becomes closer” (pg 32, lines 1-2); however, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel organoids and alveolar organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “alveolar organoid” are not disclosed.
Example 3-2 (pg 32) describes placing blood vessel organoids into a “low cell attachment plate, separating airway organoids from Matrigel, and transferring them to the plate (pg 32, lines 8-14). The combination of airway and blood vessel organoids was transferred to “STEMdiffTM blood vessel organoid maturation medium” (pg 32, line 15). Medium was removed and matrigel was added (pg 32, lines 17-19). The specification says a “certain amount of time is required for fusion depending on the distance between organoids or the size of the organoids”, but they were cultured for 2-7 days “to allow the blood vessel organoids and alveolar organoids to fuse” (sentence bridging pg 31-32). “STEMdiffTM blood vessel organoid maturation medium” was added “until fusion could be observed under an optical microscope” (pg 32, lines 19-21). However, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel organoids and airway organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “airway organoid” are not disclosed.
Example 3-3 (pg 32, line 25) analyzes the “fused” organoids. Expression of CD31 and SMA was observed (pg 33, lines 3-5). The organoids “underwent gelation after the maturation stage, resulting in the creation of new blood vessels in the organoids and extending out (Fig. 4A and 4B)” under microscopic observation. However, the amount of “closeness”, the structures, and the functions associated with “fused” blood vessel and airway or alveolar organoids are not disclosed. The amount of “closeness”, the structures, and the functions associated with a “vascularized” or “mature” “airway or alveolar organoid” are not disclosed.
The specification does not teach any non-airway, non-alveolar respiratory organoids fused with blood vessel organoids as broadly encompassed by claim 1.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to obtain the reagents required to perform the method, to perform “gelating” as required in claim 1, to “fuse” “organoids” as required in claim 1 or to determine when “vascularized respiratory organoids” had been obtained.
Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The metes and bounds of a “blood vessel organoid” in claim 1 cannot be determined. It is unclear if the phrase encompasses a blood vessel sample or fragment. It is unclear whether a blood vessel organoid must be in culture or if it encompasses in vivo embodiments like blood vessel tissue that has been transplanted. It appears to encompass culture-related blood vessel tissue culture, but it is unclear when amalgamation of cells constitute a blood vessel organoid. Blood vessels are primarily made up of endothelial cells, smooth muscle cells, and connective tissue cells. It is unclear whether one of these cell types alone in a cluster constitutes a “blood vessel organoid” or whether two or more of these cells types are required. It is unclear whether any configuration of one or more of these cells types is encompassed by the phrase or whether distinct layers or structures are required. It is unclear whether any non-functional configuration is encompassed by the phrase or whether one or more specific functions are required to be considered a “blood vessel organoid”. The specification and the art at the time of filing do not define the phrase. Therefore, this concept indefinite because those of skill would not be able to determine the metes and bounds of the phrase.
The metes and bounds of a respiratory organoid in claim 1 cannot be determined. It is unclear if the phrase encompasses any lung, nasal, or mouth tissue sample or fragment. It is unclear whether a “respiratory organoid” must be in culture or if it encompasses in vivo embodiments like respiratory tissue that has been transplanted. It appears to encompass culture-related respiratory tissue culture, but it is unclear when amalgamation of cells constitute a respiratory organoid. Respiratory tissue includes any lung, alveolar, trachea, nasal, or mouth tissue. Lung tissue is primarily made up of epithelial, goblet, basal, club, alveolar type I or II, and endothelial, as well as fibroblasts, immune cells, e.g. macrophages and neutrophils, and connective tissue cells. It is unclear whether one of these cell types alone in a cluster constitutes a “respiratory organoid” or whether two or more of these cells types are required. It is unclear whether any configuration of one or more of these cells types is encompassed by the phrase or whether distinct layers or structures are required. It is unclear whether any non-functional configuration is encompassed by the phrase or whether one or more specific functions are required to be considered a “respiratory organoid”. The specification and the art at the time of filing do not define the phrase. Therefore, this concept indefinite because those of skill would not be able to determine the metes and bounds of the phrase.
The metes and bounds of “gelating” blood vessel and respiratory tissue in claim 1 cannot be determined. The specification uses the term throughout (pg 6, description of Fig. 4; pg 29, line 9) which appears to be limited to culturing cells on Matrigel (pg 29, lines 6-10). It is unclear what other embodiments are encompassed by “gelating”. The specification uses the phrase “3D culturing” (pg 8, line 17), but all culture methods are in 3 dimensions. The specification does not contemplate using any other well-known hydrogels, e.g. collagen, fibrin, gelatin, PEG, polyacrylamide. Therefore, this concept indefinite because it is unclear what reagents and active steps are essential to accomplish “gelating” as required in claim 1.
The metes and bounds of “fusing” a blood vessel organoid and a vascularized respiratory organoid in claim 1 are unclear. It is unclear how the “fusing” in step b) is different than the “gelating” in step a) because the “gelating” may just be culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel. If so, the “fusing” is redundant and should be deleted. If it is an active step, then it is unclear what reagents and active steps are essential to accomplish the “fusing”. If it is a passive step that is simply a result of culturing a blood vessel organoid and a vascularized respiratory organoid in the presence of a hydrogel, then the structures/functions of a “fused” “mature” “blood vessel organoid”. Regardless of whether the “fusing” is active or passive, it is unclear when “fusing” occurs because the structures and functions associated with a “fused” blood vessel and vascularized respiratory organoid are not disclosed. Nor are the structures and functions associated with a “mature” blood vessel organoid disclosed. Therefore, this concept indefinite because those of skill would not be able to determine the metes and bounds of the phrase.
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, 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Vargas-Valderrama (J. Biomedical Science, 2020, Vol. 27, No. 67, pg 1-13) in view of Dye (eLIFE, 2016, Vol. 5, e19732), Sellgren (Royal Society of Chem., 2014, Vol. 14, pg 3349-3358), Benam (Nature Methods, 2016, Vol. 13, No. 2, pg 151-157).
Vargas-Valderrama taught co-culturing endothelial cells with various organoids (iPS-derived pancreas organoid+endothelial cells in Matrigel, pg 4; iPS-derived liver organoid+endothelial cells in Matrigel, pg 4-5; iPS-derived kidney organoid+endothelial cells in Matrigel, pg 5-6; iPS-derived brain organoid+endothelial cells in Matrigel, pg 6-7). The endothelial cells are “blood vessel organoids” as required in claim 1. Use of Matrigel is “gelating” as required in claim 1. The iPS cell-derived organoids exhibited increased vascularization which is proof of “fusing” and “blood vessel organoid maturation” as required in claim 1.
Vargas-Valderrama did not teach the organoid was a respiratory organoid as required in claim 1.
However, Dye taught an iPS cell-derived alveolar organoids (pg 7, last full para). Sellgren combined lung cells with endothelial cells modeling an airway organoid (abstract; pg 3349, col. 2, last sentence; pg 3350, 1st sentence). Brenam combined lung cells with endothelial cells modeling an airway organoid (abstract; pg 152, col. 1, end of 1st partial paragraph; Fig. 1B).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to coculture organoids with endothelial cells to increase vascularization of the organoid as described by Vargas-Valderrama wherein the organoid was a lung organoid described by Dye, Sellgren, or Brenam. Those of ordinary skill in the art at the time of filing would have been motivated to replace the organoids of Vargas-Valderrama with a lung organoid described by Dye, Sellgren, or Brenam to improve vascularization of lung organoids.
The endothelial cells of Vargas-Valderrama inherently MUST express CD31 and SMA as required in claim 4 because they are markers of endoethelial cells.
The lung organoids of Dye, Sellgren, or Brenam are alveolar organoids as required in claim 5 because they contain alveolar cells.
Claim 6 has been included because the steps of Vargas-Valderrama stabilized the organoid and endothelial cells so that blood vessel formation increased and “maturation” occurred.
Claim 7 has been included because the ratio of 1:5 respiratory organoid: blood vessel organoid was an obvious variant that was at the discretion of the skilled artisan.
Vargas-Valderrama, Dye, Sellgren, or Brenam taught co-culturing cells at 30-40 degrees for 10 minutes to 2 hrs (see Materials and Methods) as required in claim 8.
Vargas-Valderrama, Dye, Sellgren, or Brenam taught co-culturing cells for 1-15 days (see Materials and Methods) as required in claim 9.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Vargas-Valderrama (J. Biomedical Science, 2020, Vol. 27, No. 67, pg 1-13) in view of Dye (eLIFE, 2016, Vol. 5, e19732), Sellgren (Royal Society of Chem., 2014, Vol. 14, pg 3349-3358), Benam (Nature Methods, 2016, Vol. 13, No. 2, pg 151-157) as applied to claims 1, 4-9 and further in view of Wimmer (Nature protocols, 2019, Vol. 14, pg 3082-3100).
The combined teachings of Vargas-Valderrama, Dye, Sellgren, and Brenam taught co-culturing endothelial organoids with lung organoids (see rejection above).
The combined teachings of Vargas-Valderrama, Dye, Sellgren, and Brenam did not teach the blood vessel organoid was derived from iPS cells as required in claim 2.
However, Wimmer taught differentiating iPS cells into blood vessel organoids (title, abstract, materials and methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to coculture lung organoids with endothelial organoids as described by the combined teachings of Vargas-Valderrama, Dye, Sellgren, and Brenam wherein the endothelial organoid was a blood vessel organoid derived from iPS cells described by Wimmer. Those of ordinary skill in the art at the time of filing would have been motivated to replace the endothelial organoid of Vargas-Valderrama with the iPS cell-derived blood vessel organoid described by Wimmer to obtain vascular tissue that is specific to the cells from which the iPS cell was made. Wimmer provides further motivation by saying the iPS cell-derived blood vessel organoids are stable and functional in vivo (pg 3083, lines 2-4).
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Vargas-Valderrama (J. Biomedical Science, 2020, Vol. 27, No. 67, pg 1-13) in view of Dye (eLIFE, 2016, Vol. 5, e19732), Sellgren (Royal Society of Chem., 2014, Vol. 14, pg 3349-3358), Benam (Nature Methods, 2016, Vol. 13, No. 2, pg 151-157), Wimmer (Nature protocols, 2019, Vol. 14, pg 3082-3100) as applied to claims 1, 2, 4-9 and further in view of Koh (Stem Cell Res., 2022, Vol. 60, 102674, pg 1-4).
The combined teachings of Vargas-Valderrama, Dye, Sellgren, Brenam, Wimmer taught co-culturing iPS cell-derived blood vessel organoids with lung organoids (see rejection above).
The combined teachings of Vargas-Valderrama, Dye, Sellgren, Brenam, Wimmer did not teach the iPS cells were derived from umbilical cord cells as required in claim 3.
However, Koh taught reprogramming umbilical cord cells into iPS cells (title, abstract, materials and methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to coculture lung organoids with iPS cell-derived blood vessel organoids as described by the combined teachings of Vargas-Valderrama, Dye, Sellgren, Brenam, Wimmer, wherein the iPS cells were reprogrammed from umbilical cord cells as described by Koh. Those of ordinary skill in the art at the time of filing would have been motivated to replace the fibroblast-derived iPS cells described by Wimmer with the umbicilical cord-derived iPS cells described by Koh because Koh taught umbilical cells had several advantages, e.g. higher proliferation and stemness, less immune rejection, fewer nuclear and mitochondrial mtuations (pg 3, col. 1).
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights