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 status
Applicants reply filed 12/8/2025 is acknowledged.
Claims 12, 13 is/are cancelled and claims 27 is/are newly added. Claims 1, 3, 4, 6, 7, 11, 14-16, 18-27 is/are currently pending with claims 4, 6, 7 is/are withdrawn. Claims 1, 3, 11, 14-16, 18-27 is/are under examination.
Claim Objections
Applicant is advised that should claim 11 be found allowable, claim 22 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. Both claim 11 and 22 recite collagen component of average length 1nm to 1mm. Although claim 11 also recites the average diameter of 10nm to 100um, this limitation is already recited in claim 1 and thus is included in claim 22 as well. Thus, claims 11 and 22 recite collagen component of the same structure.
Applicant is advised that should claim 1 be found allowable, claim 25 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. Claims 25 comprises each of the limitations from claim 1 and repeats the limitation regarding the range of average diameter already recited in claim 1. Thus, claims 1 and 25 recite a tissue of the same structure.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Interpretation – Updated to address claim amendments
Claim 1 is a product claim directed to a “self-organizing” brain blood vessel model, comprising a three-dimensional tissue comprising “defibrated collagen components” and the recited cell types.
Regarding, “self-organizing”, the specification states that “[0065] "Self-organization" is a phenomenon in which tissue is naturally formed by interactions of constituent elements themselves. A brain blood vessel model formed through self-organization is not particularly limited, but can be formed, for example, by culturing defibrated extracellular matrix components, cells including brain microvascular endothelial cells, pericytes, and astrocytes, and as necessary, the above-described other components.” Considering the claim is directed to an in vitro model, natural interactions between constituent elements (i.e. cells and the collagen components) are broadly understood to embrace any interaction between the cells and/or between the cells and the collagen that are reasonably similar to interactions observed in a non-artificial environment.
Of note, the claim does not require the constituent elements of the three-dimensional tissue to be completely “self-organized” since it recites that the tissue comprises a “pre self-organization state” (line 3). The claim further uses ‘product-by-process’ claim language to limit the “pre self-organization state” (see wherein clause).
According to MPEP 2113, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
Herein, the product-by-process limitation “wherein in the pre self-organization state, the cells are brought into contact with the defibrated collagen components dispersed in an aqueous medium without support from a non- collagen scaffold and cultured such that at least a portion of the cells adhere to the defibrated collagen components that have formed a scaffold and the portion of the cells adhered to the defibrated collagen components are in a state of self-organization”, is interpreted to provide the following structure to the claimed three-dimensional tissue:
The tissue comprises the recited cells and the collagen matrix with the claimed structure (positively recited in the lines 4-7) such that at least a portion of the cells have adhered to the collagen matrix and these adhered cells are “self-organized” while some cells may not have adhered, thus are still in a “pre self-organization state”. The tissue does not comprise non-collagen scaffold (see underlined portion above).
Further, the product-by-process limitation “the portion of the cells adhered to the defibrated collagen components are in a state of self-organization in which the portion of the cells self-organize with support from the scaffold to form the brain blood vessel model including a brain blood vessel tube network in which a plurality of brain blood vessel tubes are distributed and that includes a plurality of openings therebetween brain blood vessel tubes among the plurality of brain blood vessel tubes.”, is interpreted to provide the following structure to the claimed three-dimensional tissue:
The blood-brain vessel model is formed by the portion of cells that have adhered to the collagen-only scaffold and this portion form the brain blood vessel tube network with the recited structure i.e. network of vessels with plurality of openings within.
Regarding “defibrated collagen components “, the claim positively recites the following structure: average length range, average diameter range and that “wherein bonds of molecules in the defibrated collagen components are not cleaved” (lines 4-7).
The claim further recites a process step for the derivation of the defibrated collagen components –“defibration of extracellular matrix components by a homogenizer or by repeated freezing and thawing”. Therefore, the claim is a product-by-process claim. See discussion from MPEP 2113 above.
In the instant case, the process steps provide the following structure to the defibrated collagen components: “bonds of molecules in the defibrated collagen components are not cleaved”. Therefore, the broadest reasonable interpretation of the phrase “defibrated collagen components” are collagen molecules that are mixed in solution using physical means such that the collagen molecule have the structure as positively claimed.
Claim Rejections - 35 USC § 112(b)- New, necessitated by claim amendments
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.
Previous rejection of Claims 1, 3, 11-15 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 is moot and/or withdrawn in light of claim amendments.
Claims 3, 18 and 19 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.
Claim 3 recites “wherein the three-dimensional tissue further includes fibrin”. It is unclear how fibrin is included in the structure of the tissue of claim 1. According to interpretation of the product-by-process limitations in claim 1 (see above), the tissue comprises collagen-only scaffold. Claim 1 explicitly requires the cells to be brought in contact with collagen without support from a non-collagen scaffold and cultured with only this collagen such that the cells adhere to this collagen scaffold. It appears that the claim is broadening the scaffold of claim 1 by including fibrin (see U.S.C. 112d rejection below). Since fibrin is also a culture scaffold and used as a mixture with collagen, it is unclear how is fibrin included in the structure of the tissue of claim 1. In the instant specification, when fibrin is used as a culture scaffold it is mixed with collagen and an additional scaffold in the form of a pressure-driven micro-flow path device is used (Example 8). Thus, it appears that instant claim 1 is now directed to an embodiment that explicitly excludes the embodiment in Example 8.
Reasonable interpretation and application of prior art is inhibited due to this contradiction between claim 1 and 3. Additional rejections and art may be applied in a subsequent final Office action upon clarification of issues with claim 3.
Claim 18, 19 is/are rejected due their dependence on claim 3 because they do not clarify the 112b issue noted with claim 3.
Claim Rejections - 35 USC § 112(d) – New, necessitated by claim amendments
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3, 11, 22, 24 and 25 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 appears to broaden the scaffold of claim 1. See analysis in U.S.C. 112b rejection above.
Claims 11 and 22 broadens the range of average length of collagen. Claim 1 recites that the smallest length is 10nm, thus claims 11 and 12 broaden the average length to now include 1nm i.e. smaller than 10nm.
Claims 24 broadens the range of average length of collagen. Claim 1 recites that the smallest length is 10nm, thus claim 24 broaden the average length to now include 1nm i.e. smaller than 10nm.
Claims 25 fails to limit claim 1 because it recites the same average diameter range as claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a) -New Matter; Withdrawn
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.
Rejection of Claims 1, 3, 11-15 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 is withdrawn because new matter is removed from amended claim 1.
Claim Rejections - 35 USC § 102 - Withdrawn
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Rejection of Claim(s) 1, 11 and 12 under 35 U.S.C. 102(a)(1) as being anticipated by Herland et al (PLOS ONE; March 1, 2016; ref of record) as evidenced by Application notes and FAQs for Corning Collagen I, Rat Tail (Product Number 354236; ref of record) and Meyer et al (BioMed Eng OnLine (2019) 18:24; ref of record) and Xie et al (Collagen Gels with Different Fibrillar Microarchitectures Elicit Different Cellular Responses. ACS Appl. Mater. Interfaces 2017, 9, 19630−19637) is withdrawn in light of claim amendment requiring collagen-only scaffold.
Claim Rejections - 35 USC § 102/103 - Withdrawn
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
Rejection of Claim(s) 14, 15 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Herland et al (PLOS ONE; March 1, 2016; ref of record) as evidenced by Application notes and FAQs for Corning Collagen I, Rat Tail (Product Number 354236; ref of record) and Meyer et al (BioMed Eng OnLine (2019) 18:24; ref of record) and Xie et al (Collagen Gels with Different Fibrillar Microarchitectures Elicit Different Cellular Responses. ACS Appl. Mater. Interfaces 2017, 9, 19630−19637) is withdrawn because of withdrawal of U.S.C. 102 rejection of claim 1 based on Herland, that this rejection relied upon.
Claim Rejections - 35 USC § 103 – New, necessitated by claim amendments
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.
Rejection of Claim(s) 13 under 35 U.S.C. 103 as being unpatentable over Herland et al (PLOS ONE, March 1, 2016; ref of record) as evidenced by Application notes and FAQs for Corning Collagen I, Rat Tail (Product Number 354236; ref of record) and Meyer et al (BioMed Eng OnLine (2019) 18:24) and Xie et al (Collagen Gels with Different Fibrillar Microarchitectures Elicit Different Cellular Responses. ACS Appl. Mater. Interfaces 2017, 9, 19630−19637) is withdrawn because of withdrawal of U.S.C. 102 rejection of claim 1 based on Herland, that this rejection relied upon.
Rejection of Claim(s) 1, 3, 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herland et al (PLOS ONE, March 1, 2016; ref of record) and Campisi et al (Biomaterials 180 (2018); ref of record), in view of Cummings et al (Biomaterials 25 (2004) 3699–3706; ref of record) as evidenced by Application notes and FAQs for Corning Collagen I, Rat Tail (Product Number 354236; ref of record) and Meyer et al (BioMed Eng OnLine (2019) 18:24) and Xie et al (Collagen Gels with Different Fibrillar Microarchitectures Elicit Different Cellular Responses. ACS Appl. Mater. Interfaces 2017, 9, 19630−19637) is withdrawn because of withdrawal of U.S.C. 102 rejection of claim 1 based on Herland, that this rejection relied upon.
Claim(s) 1, 11, 14-16, 20-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herland et al (PLOS ONE, March 1, 2016; ref of record) in view of Komeda et al (Polymer Preprints, Japan, 2017; Original and English translation in IDS 9/21/2021)
Regarding claim 1, Herland teaches a brain blood vessel model comprising brain microvascular endothelial cells, pericytes and astrocytes in a collagen scaffold (Cell culture in three-dimensional gels). Herland teaches that in the brain blood vessels the microvascular endothelial cells are surrounded by pericytes and astrocytes (Introduction, para 2). Herland teaches that attempts to co-culture microvascular endothelial cells, pericytes and astrocytes to form a 3D spheroid had been made but in such spheroids vessels remained on the outside of the sphere and no vessel network formed on the inside (page 3, para 1). Herland attempts to overcome this lack of vessels on the inside of the 3D tissue by developing a multi-step method that takes at least 24 hours to perform (Cell culture in three-dimensional gels). Herland’s method comprises mixing collagen with astrocytes, then treating this collagen scaffold mixed with astrocytes to hydrostatic pressure in a microfluidic device to from a singular central lumen, then flowing pericytes and subsequently endothelial cells into the scaffold (Figure 1C, 2; Cell culture in three-dimensional gels).
Regarding claim 27, Herland teaches that the cells of the blood brain vessels (i.e. microvascular endothelial cells, pericytes and astrocytes) in their 3D model self-organize and allow for transport which would inherently require expression of transporters, express ZO-1 tight-junction protein, VE-Cadherin vascular endothelial cell marker (Figure 4, S1, 2 ; Fixation, staining and imaging).
Compared to Herland, Komeda teaches a simple technique to form three-dimensional blood vessel model wherein the blood vessel network is dispersed throughout the tissue (Figure 1; Introduction, para 3). Briefly, Komeda’s method simply comprises mixing defibrated collagen with endothelial cells and allowing them to self-organize (Experiment).
Regarding claim 1, Komeda’s method results in a three-dimensional tissue comprising defibrated collagen components and cells (see Experiment, para 1; Figure 1), wherein the cells adhere to the collagen scaffold and self-organize to form blood vessels (see Introduction, para 3; Figure 3). Komeda teaches that the self-organized blood vessel tissue comprises a capillary network (=claimed a network of blood vessels; Figure 3; see Results and Discussion, para 2) with a plurality of spaces in between due to gaps between the collagen components (=claimed openings; Figure 3; see Results and Discussion, para 3 and 4).
Regarding the structure of defibrated collagen components claimed in claims 1, 11, 22, 23 and 25, Komeda teaches collagen components having an average length of 80±32um (=claimed range 10nm to 1mm in claim 1, or 1nm to 1mm in claims 11 and 22, or 22um to 400um in claim 23) and average diameter of 15±5.1um (=claimed range 10nm to 100um in claim 1 and 25), wherein the collagen is defibrated by homogenization and the bonds of the molecules are not cleaved (see Results and Discussion, para 1).
Regarding claims 20 and 21, Komeda teaches that their tissue comprises 27 wt% collagen (=claimed mass% range of 10-50% in claim 20 and 20-30% of claim 21; see Results and Discussion, para 2).
Regarding claims 14 and 15, Komeda teaches that their tissue comprises 105 cells with 20% of total cells being endothelial cells (see Results and Discussion, para 2). Since Komeda’s tissue comprises collagen at 27% of the weight, the wt% of cells is estimated to be less than 73%. An ordinary artisan could further optimize the wt% of cells in a 3D tissue to be between 25-75%, as claimed in claim 15, and such an optimization would be considered routine. According to MPEP 2144.05 (II), “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, an ordinary artisan would optimize the wt% of cells in the 3D tissue to generate a tissue of desired size and coverage of the collagen scaffold. To this end, the specification does not disclose the wt% of cells in the tissue produced and cannot establish criticality of this claimed limitation. Furthermore, “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").” See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). Therefore, in teaching a 3D tissue with 27 wt% collagen and thus cells at a wt% of at least 73%, Komeda renders the instant wt% of cells claimed in claims 14 and 15 prima facie obvious.
Regarding claim 16, Komeda’s 3D tissue appears to be an irregular sphere and not tubular, as claimed (Figure 3). According to MPEP 2144.04 (IV) (B), “In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966) (The court held that the configuration of the claimed disposable plastic nursing container was a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular configuration of the claimed container was significant.).” In the instant case, the specification does not disclose significance of the shape of the tissue or if the tissue produced was tubular. In fact, same as Komeda, the tissue produced in the instant specification also appears to be an irregular sphere (Figure 1). Furthermore, Komeda’s method results in a spherical shape since the tissue is cultured in a 96-well micro plate that have semi-spherical bottom (Experiment). An ordinary artisan choosing a different shape, such as tubular, for their 3D tissue would use a differently shaped culture vessel to produce their 3D tissue. Therefore, in teaching a 3D tissue with an irregular spherical shape, Komeda renders the instantly claimed tubular shape prima facie obvious.
Regarding claim 24, the range of average length claimed is 1nm to 30um. Komeda teaches the length of defibrated collagen is 80±32um i.e. 48-112um (see Results and Discussion, para 1). According to MPEP 2144.05 (I), “A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close”. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%). Similarly, see In re Lilienfeld, 67 F.2d 920, 924, 20 USPQ 53, 57 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"). In the instant case, although the claimed average length in 1nm to 30um, the average length of defibrated collagen produced in the instant specification is 100-200um (page 26, last para). The length of Komeda’s defibrated collagen approaches the claimed average length and overlaps with the average length disclosed in the instant specification. Additionally an average length of 30um as claimed allows for the actual length of collagen fibers in the defibrated collagen to be greater than 30um such as about 80um, as taught by Komeda. A criticality of claimed range cannot be established. Therefore, in teaching a length of 48-112um, Komeda renders the instantly claimed 1nm to 30um prima facie obvious.
Regarding claim 26, the range of average diameter claimed is 20-30um. Komeda teaches the diameter of defibrated collagen is 15±5.1um i.e. 9.9-20.1um (see Results and Discussion, para 1). According to MPEP 2144.05 (I), “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” See In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range). In the instant case, both Komeda’s and instantly claimed defibrated collagen lead to the same end point of collagen microfibers that when mixed with cells produce a vascularized tissue with openings in between the tissue. Additionally an average diameter of 20um as claimed allows for the actual diameters of collagen fibers in the defibrated collagen to be less than 20um such as about 15um, as taught by Komeda. A criticality of claimed range cannot be established. Therefore, in teaching a diameter of 9.9-20.1um, Komeda renders the instantly claimed 20-30um prima facie obvious.
The combination of prior art cited above under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S., 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness are from MPEP 2143.
In the present situation, rationale (C) Use of known technique to improve similar devices (methods, or products) in the same way is applicable. MPEP 2143 guides that for rationale C “Office personnel must articulate the following: (1) a finding that the prior art contained a "base" device (method, or product) upon which the claimed invention can be seen as an "improvement;" (2) a finding that the prior art contained a "comparable" device (method, or product that is not the same as the base device) that has been improved in the same way as the claimed invention; (3) a finding that one of ordinary skill in the art could have applied the known "improvement" technique in the same way to the "base" device (method, or product) and the results would have been predictable to one of ordinary skill in the art; and (4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness.
(1) The prior art of Herland comprised a base product of a brain blood vessel model comprising the claimed cells in a collagen scaffold, produced by a complex and time-consuming method and resulting in a singular lumen in the 3D tissue produced. In comparison, the claimed tissue comprises a network of blood vessels and a plurality of openings produced by the recited product-by-process limitations.
(2) The prior art of Komeda teaches a technique to improve 3D tissue that do not have a network of blood vessels with a plurality of openings inside the tissue. Komeda teaches a simple and fast technique of combining defibrated collagen (with features similar to claimed defibrated collagen) with endothelial cells to produce 3D tissue with a network of blood vessels and a plurality of openings.
(3) An ordinary artisan would apply Komeda’s technique to Herland’s brain blood vessel model by combining Komeda’s defibrated collagen with Herland’s cells (brain microvascular endothelial cells, astrocytes and pericytes). An ordinary artisan would reasonably predict that application of Komeda’s technique to Herland’s brain blood vessel model would produce a self-organizing 3D blood brain vessel wherein the endothelial cells, astrocytes and pericytes organize via natural interactions between these cells. An ordinary artisan would be motivated to apply Komeda’s technique to Herland’s brain blood vessel model because it would allow for a brain blood vessel model with a network of blood vessels and a plurality of openings. The simplicity and rapidity of Komeda’s method are further motivating factors to apply their technique to produce vascularized 3D tissue.
Therefore, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR. Therefore, it would be obvious to a person of ordinary skill in the art to use Komeda’s method to improve Herland’s brain blood vessel model.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 11, 14-16, 20-27 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
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