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 .
Detailed Action
The Examiner for this Application has changed. Please direct all future correspondence to Patent Supervisor Examiner Maria Leavitt, AU 1634. Additional contact information can be found at the end of this paper.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on June 23, 2025. Claims 1-7 are currently pending. Claim 1 has been amended. No claims were canceled or added.
Therefore claims 1-7 are currently under examination to which the following grounds of rejection applied.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2020/055043, filed October 9, 2020.
Acknowledgement is made of Applicant’s claim for benefit of prior-filed US Provisional application 62/913,226 (filed 10/10/2019).
Thus, the earliest possible priority for the instant application is October 10, 2019.
Remaining Rejections in response to Applicants’ arguments or amendments
Claim interpretation
Comparative table of reagents used in culture media disclosed in WO 2019/133810, claim 1 of the instant invention and the SQM Medium (paragraph [0496] of the published application).
WO 2019/133810
Claim 1
SQM Medium
(1 Liter)
a ROCK (Rho Kinase) inhibitor
a ROCK (Rho Kinase) inhibitor
Y-27632
1 ml
a Wnt agonist
a mitogenic growth factor
A mitogenic growth factor,
epidermal growth factor (EGF)
hydrocortisone
1 ml
2 ml
Insulin or IGF
insulin or IGF
Insulin
1 ml
a BRAF inhibitor
a VEGF inhibitor
a VEGF inhibitor
nicotinamide
a Notch Agonist,
a TGFl3 signaling pathway inhibitor
BMP antagonist
noggin
1 ml
a TrkA Inhibitor
GW441756
500 uL
Oct4-activating agent
an Oct4-activating agent
a VEGF inhibitor
a tyrosine kinase inhibitor
Tivozanib
Potatinib
500 uL
500 uL
DMEM
645 ml
F12
215 ml
FBS
100 ml
L-glutamine
10 ml
Adenine
10 ml
Pen/strep
10 ml
thyroid hormone signaling pathway activator-
T3 (3,3" ,5-Triiodo-L-Thyronine
2 ml
WNT signaling inhibitor SB43152
1 ml
hFGF10
1 ml
Claim Rejections - 35 USC § 103
Claims 1 – 7 remain rejected under 35 U.S.C. 103 as being unpatentable over Xian et al (WO 2019/133810 A1 – 2019, of record cited by Applicant; hereinafter Xian et al – 2019), in view of Xian et al (WO 2018/204913 A1 - 2018, of record cited by Applicant; hereinafter Xian et al – 2018) and in further view of Schmidt et al (US 10,258,628 B2 – 2019, of record cited by Applicant; hereinafter Schmidt et al – 2019). This rejection has been modified as necessitated by amendment of the claims in the responses filed June 23, 2025.
Claim 1 has been amended to exclude R-Spondin, Jagged-1 and nicotinamide from the defined culture medium for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture.
Regarding Claim 1, Xian et al – 2019 teaches a defined culture medium for isolating and stably maintaining the epigenetics of columnar epithelial stem cells through a plurality of passaging in culture, the medium comprising: a basal medium, a ROCK (Rho Kinase) inhibitor; a Wnt agonist; a mitogenic growth factor; insulin (or an insulin mimetic) or IGF; a BRAF inhibitor; a VEGF inhibitor; nicotinamide; a Notch Agonist, a TGF signaling pathway inhibitor; and a Bone Morphogenetic Protein (BMP) antagonist, and wherein media supports the epigenetically stable growth and proliferation of stem cells of columnar epithelial tissue origin in the presence and in the absence of cocultured feeder cells (see Claims 14 - 15 | Page 110). Furthermore, Xian et al – 2019 teaches in certain embodiments, the VEGF Receptor inhibitor is a multi-tyrosine kinase inhibitor (see Lines 25 – 26 | Page 44). This reads on a tyrosine kinase inhibitor. To continue, Xian et al – 2019 teaches in certain embodiments, a combination of mitogenic growth factors, such as…. FGF10, is added to the subject culture medium (see Lines 31 – 33 | Page 31). Additionally, Xian et al – 2019, teaches, an Oct4-activating agent (see Line 8 | Page 5). Furthermore, Xian et al – 2019 teaches “pseudostratified columnar epithelium” is columnar epithelia which, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia (see Lines 26 – 29 | Page 19). This reads as stratified epithelial stem cells. In preferred embodiments, Xian et al-2019 teaches that nicotinamide is in the cultured medium (Xian et al – 2019, claim 1). Because R-Spondin and Jagged-1 are not components of Xian et al-2019 culture medium, R-Spondin and Jagged-1 are excluded from said culture medium.
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However, in non-preferred embodiments Xian et al – 2019 teaches that the culture medium of the inventions “may additionally be supplemented with nicotinamide or its analogs, precursors, or mimics, such as methyl-nicotinamide benazamid, pyrazinamide, thymine, or niacin.” (under the heading of Nicotinamide, lines 7-10).
Thus, it would have been obvious for one of ordinary skill in the art to optionally exclude nicotinamide from culture media supporting epigenetically stable growth and proliferation of stem cells with a reasonable expectation of success depending on media supplementing components used, their concentration, culture conditions and others since where the general conditions of a claim are disclosed in the prior art, the conducting of routine experimentation in order to discover or determine optimum or workable ranges is not inventive.
It is no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable (MPEP 2144.05). 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. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Xian et al – 2019, does not teach, a TrkA inhibitor.
Xian et al – 2018 teaches therapeutic agents that may be attached to specific affinity binder polypeptides for selective killing of IBD stem cells or IBD stem cell derived tissues include, but are not limited to…..tyrosine kinase inhibitors (see Lines 23 – 29 | Page 93) and examples of tyrosine kinase inhibitors include (see Lines 28 – 33 | Page 95), but are not limited to……FLT3 (Lestaurtinib) and Janus kinase 2 (Lestaurtinib). Moreover, Xian et al – 2018 teaches one aspect of the invention provides isolated epithelial stem cells derived from gastrointestinal biopsies from IBD patients, referred to herein as “IBD Stem Cells” (see Lines 27 – 28 | Page 2). The instant application teaches Lestaurtinib is a TrkA inhibitor (see Lines 18 – 20 | Page 6). To continue, Xian et al – 2018 teaches “Inflammatory bowel disease”, or “IBD”, is a term (Lines 30 – 32 | Page 14) that encompasses both ulcerative colitis (inflammation of the lining of the large intestine) and Crohn’s disease (inflammation of the lining and wall of the large and/or small intestine). Xian et al – 2018 teaches IBD stem cells as being epithelial stem cells (see Lines 3 – 5 | Page 151). A “specific affinity binder” refers to an antibody as well as to a non-antibody protein scaffold i.e., smaller proteins that are capable of achieving comparable affinity and specificity using molecular structures that can be for example one-fifth to one-tenth the size of full antibodies, and also to nucleic aptamers (Lines 15 – 19 | Page 16). To continue, Xian et al – 2018 teaches in certain embodiments, the subject invention also provides specific affinity binders, such as antibodies, which selectively bind to a polypeptide gene expression product of a pCD Gene Sequence or other protein that is upregulated in a population of IBD stem cells or its progeny, preferably a protein expressed on the cell surface of the IBD stem cell or its progeny. The binding of the antibody can result in inhibition of the function of the cell, such as proliferation or differentiation of IBD stem cells or progeny, cell death, or alteration of the function of the cell in the tissue (see Lines 36 – 37 | Page 90 | and Lines 1 – 5 | Page 91).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Xian et al – 2019, to incorporate Lestaurtinib (TrkA inhibitor) as taught by Xian et al – 2018. This would be to have an agent (TrkA inhibitor), used as a component of a specific affinity binder, which can inhibit functions of the stem cell when deemed appropriate. This includes manipulation of stem cell function including inhibition of the function of the stem cell such as proliferation or differentiation, cell death or alteration of the function of the cell in the tissue as disclosed by Xian et al – 2018 (see Lines 36 – 37 | Page 90 | and Lines 1 – 5 | Page 91).
A person of ordinary skill in the art would have been motivated for doing so given Xian et al – 2018 teaches TrkA inhibitors can be used as a stem cell culture ingredient for a method of isolation of IBD stem cells from tissue samples, such as biopsies, the method can be performed by culturing dissociated epithelial cells from an IBD tissue sample in the medium, isolating single cells from the epithelial cell clones that arise, and culturing the isolated single cells from to form individual cultures of single cell clones (see Lines 25 – 31 | Page 32). Such ingredients facilitate the passaging and maintenance of the subject IBD stem cells (see Line 3 - 6 | Page 151). This is in agreement with the invention of Xian et al - 2019 which discloses a method for isolating a stem cell from epithelial tissue, preferably from columnar epithelial tissue, e.g., normal or diseased tissue, the method comprising: (1) culturing dissociated epithelial cells from a columnar epithelial tissue sample to form stem cell colonies, wherein the dissociated cells and cell colonies are cultured in a medium (see Lines 23 – 28 | Page 3). Among the objectives of Xian et al – 2019 is a defined culture medium for isolating and stably maintaining the epigenetics of columnar epithelial stem cells through a plurality of passaging in culture (see Lines 23 – 24 | Page 110). Several of the stem culture medium ingredients of Xian et al – 2019 (see Page 3 | Line 23 to | Page 6 | Lines 1 – 22) are shared by Xian et al – 2018 (see Lines 15 – 20 | Page 32) and also disclosed by the instant application (see Lines 13 – 20 | Page 3 and Lines 18 – 20 | Page 6). Hence, the inclusion of TrkA inhibitors would not inhibit the intended objective of Xian et al – 2019.
There is a reasonable expectation of success given that already several of the ingredients for the isolation of stem cell cultures that are in Xian et al - 2019, match the ingredients for the same objective found in Xian et al 2018. Hence, there is compatibility for the incorporation of a TrkA inhibitor from Xian et al 2018, into the methods of Xian et al – 2019.
Regarding Claim 2, Xian et al – 2019 teaches, in one aspect, the invention provides a method for isolating a stem cell from epithelial tissue, preferably columnar epithelial tissue, e.g., normal or diseased tissue, the method comprising (see Lines 23 – 25 | Page 3), wherein the cells from the tissue sample are optionally in fluid or direct contact with mitotically inactive feeder cells, or are cultured in the absence of feeder cells (see Lines 8 – 10 | Page 4). Furthermore, Xian et al – 2019 teaches, a GSK inhibitor (see Lines 24 – 26 | Page 10). To continue, GSK-inhibitors comprise….FRAT-derived peptides that prevent interaction of GSK-3 with axin (see Lines 26 – 30 | Page 29).
Xian et al – 2019 does not teach a SYK inhibitor, an LPA receptor antagonist, nor a CK2 inhibitor as elements of a defined culture medium.
Schmidt et al – 2019 teaches, cerdulanatib, an SYK inhibitor (see Example 5/Table 4: representative biologically diverse chemical series tested | Pages 72 - 73) is included as part of defining the claims that are the scope of the invention described in Schmidt et al - 2019 (see column 65, IX. Examples, Lines 21 – 27 | Page 70). This applies also to CK2 inhibitors (see Example 5/Table 4: representative biologically diverse chemical series tested | Pages 72 - 73). To continue, Schmidt et al – 2019 teaches, according to the methods provided herein, small molecules that are known or suspected to target networks and pathways related to muscle development may be used for drug screening assays. The small molecules may have known or suspected targets that are Class A G-protein coupled receptors, including, but not limited to:…… LPA1, LPA2, LPA3, LPA4, LPA5, LPA6 (see column 53, Lines 11 - 12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Xian et al – 2019 in view of Xian et al – 2018, to incorporate the teachings of Schmidt et al - 2019, whereas an SYK inhibitor, such as cerdulanatib, an LPA receptor antagonist and CK2 as mentioned in Table 4 of Schmidt et al – 2019 are included in cell culture media. A person of ordinary skill in the art would have been motivated to do so because, such agents can be used to modulate specific pathways and networks to obtain specific cell differentiation and/or proliferation of a cell culture (see Column 68, Lines 55 - 65 | Page 71). There is a reasonable expectation of success given that the compounds/elements described are in use by those with ordinary skill in the art for the purposes of cell differentiation and/or proliferation of a cell culture, compatible with the claimed invention.
Regarding Claim 3, Xian et al – 2019 teaches, the invention provides a method for isolating a stem cell from epithelial tissue, preferably columnar epithelial tissue, e.g., normal or diseased tissue, the method comprising (see Lines 23 – 25 | Page 3):…wherein the wherein the cells from the tissue sample are optionally in contact with extracellular matrix (such as a basement membrane matrix) or other bio- or synthetic matrix (see Lines 14 – 15 | Page 6).
Regarding Claim 4, Xian et al – 2019 teaches, the invention relates to a culture media system that is useful for the isolation and epigenetically stable propagation of normal stem cells in culture which are derived from columnar epithelial tissues (see Abstract).
Regarding Claims 5 - 6, Xian et al – 2019 teaches, another aspect of the invention provides the use of epithelial stem cells, or the progeny thereof, isolated from a diseased epithelial tissue utilizing a culture medium system of the present invention (see Lines 25 – 27 | Page 14). To continue, the diseased epithelial tissue can be, for example, from a patient with an inflammatory disease or a tumor (see Lines 30 - 34 | Page 14).
Regarding Claim 7, Xian et al – 2019 teaches in its claim 1(iii), a clonal expansion of an epithelial stem cell present in the columnar epithelial tissue sample, thereby isolating epithelial stem cells. As explained prior, Xian et al – 2019 teaches “pseudostratified columnar epithelium” is columnar epithelia which, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia. This, in combination with Claim 1 (iii) of Xian et al – 2019, reads as clonal stratified epithelial stem cells. Following the discussion of Claim 1, Xian et al – 2019, in view of Xian et al – 2018, teaches the claim element ingredients of the defined culture medium of Claim 1 of the instant application.
Response to Applicants’ Arguments as they apply to rejection of claims 1-7 under 35 USC § 103
At pages 5-6 of the remarks, Applicants essentially argue that : 1)” the alleged Trka inhibitor taught by Xian-2018 is not an element of a defined culture media as recited in the present claims…. Tyrosine kinase inhibitors taught by Xian-2018 include Lestaurtinib. In view of these teachings, one of skill in the art would be taught by Xian-2018 to construct an antibody kinase-drug conjugate comprising Lestaurtinib for selective killing of IBD stem cells or IBD stem cell derived tissues. Thus, one of skill would not consider the antibody-kinase drug-conjugate teachings of Xian-2018 combine them with Xian-2019 to arrive at a defined culture medium comprising, among other things, a TrkA inhibitor as presently claimed” and 2) “None of the cited references teaches or suggests exclusion of Jagged-I, nicotinamide and R-spondin. In contrast, each of Xian-2019 and Xian-2018 teaches a culture medium which includes a Wnt agonist (e.g., R-Spondin), a Notch agonist (e.g., Jagged-1), and nicotinamide (claim 1).” Applicants’ arguments have been respectfully considered but have not been found persuasive.
Regarding 1) at the outset the examiner notes that the instant claims require a TrkA inhibitor, but the instant claims are not so limited such that unconjugated peptides are the only possible forms for the claimed TrkA inhibitors. The claims are "open" and thus lend themselves to additional media reagents, or additional forms of polypeptides/ protein including affinity binder polypeptides or antibodies. There is not requirement that the instant claims are so limited to exclude an antibody kinase-drug conjugate as argued by Applicants. Therefore, the disclosure of Xian et al – 2018 on Lestaurtinib as a TrkA inhibitor to selectively inhibit function of inflammatory bowel disease (IBD) stem cells, such as proliferation or differentiation of IBD stem cells or progeny, cell death, or alteration of the function of the cell in the tissue (see Lines 36 – 37 | Page 90 | and Lines 1 – 5 | Page 91) is relevant, since among the objectives of Xian et al – 2019 is a defined culture medium for isolating and stably maintaining the epigenetics of columnar epithelial stem cells through a plurality of passaging in culture and, moreover, several of the stem culture medium ingredients of Xian et al – 2019 are shared by Xian et al – 2018 (see Lines 15 – 20 | Page 32) and also disclosed by the instant application (see Lines 13 – 20 | Page 3 and Lines 18 – 20 | Page 6). Hence, the inclusion of TrkA inhibitors even in the form of antibody-kinase drug-conjugate according to Xian et al – 2018 for selective killing of IBD stem cells or IBD stem cell derived tissues would not inhibit the intended objective of Xian et al – 2019 (e.g., a defined culture medium for isolating and stably maintaining the epigenetics of columnar epithelial stem cells through a plurality of passaging in culture) and the combination of Xian et al – 2018 and Xian et al – 2019 renders obvious claim 1 .
Regarding 2), though the culture medium Xian et al – 2019 requires a ROCK (Rho Kinase) Inhibitor and a Wnt agonist, there is not requirement that those are R-Spondin and Jagged-1. Xian et al – 2019 discloses various ROCK inhibitors (page 11, lines 14-19) and Wnt agonists (page 11, lines 23-25; page 30, lines 4-22) were each of the species of agonists in the defined culture medium for isolating and stably maintaining the epigenetics of columnar epithelial stem cells through a plurality of passaging in culture will lead to different results (e.g., inhibitor concentration, reagents, culture conditions, cell passages, feeder-free conditions, source of epithelial stem cells and others). For example, Zhang et al (Cell Rep . 2018 Oct 16;25(3):598-610; of record IDS filed 7/9/2024, discloses that the synergistic effect of inhibition of A83-01( a TGF-β inhibitor) and Y-27632(a PAK1-ROCK-Myosin II inhibitor), in low calcium conditions (e.g., EpiX medium), supports extended expansion of epithelial stem cells in 2D format (“we found that TGF-β signaling inhibitor (0.5–2 μM A83-01) and ROCK inhibitor (5–10 μM Y-27632) synergistically promoted epithelial cell proliferation (Figures 1B and S1)” ; page 4, para 1). Moreover, Zhang et al., discloses that when increasing C2+ above 1 mM, HFKs (Human Foreskin Keratinocytes) cultured at the air-liquid interface (ALI) matured into stratified epithelium after 2 weeks (page, 6, para 2; Figure 4F). Thus, the prior art support specific reagents and concentrations in a culture medium, e.g, EpiX medium, for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture concentration for synergistic effect.
New grounds of rejection in response to Applicants’ arguments or amendments
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.
Claims 1-7 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to a defined culture medium for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture. The instant specification only discloses two exemplary defined culture media, i.e., SQM medium and SGM-63+ medium that are used for isolation and long-term expansion of primary cells, particularly long-term expansion of various types of human epithelial stem cells derived from the lung, esophagus, stomach, small intestine, colon, intestinal metaplasia, fallopian tube, kidney, pancreas, bladder, liver, or gastric system, or a portion/section thereof for regenerative medicine (para. [0082], [0463], [0491]) .
To provide adequate written description and evidence of possession of the claimed genus of amatoxin conjugate (i.e. amatoxin conjugated to any antibody that binds to a tumor-associated antigen), the instant specification can structurally describe representative conjugates or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
The specification as filed provides one example in paragraph [0491] of the SQM medium “tested and proven to support robust growth of epithelial stem cells derived from human tissues or other mammals in the presence of the irradiate feeder of mouse fibroblast cells (3T3-
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J2). For example, lung stem cells, esophagus stem cell, bladder stem cells and ovarian cancer stem cells, can all grow robustly in this culture system that comprises SQM medium, along with irradiated 3T3-J2 feeders in the illustrated example.” The concentration of each component per liter in SQM medium is presented in paragraph [0496]. A second example of tested and proven medium to support robust growth of epithelial stem is identified as the SGM-63+ medium (“The SGM-63+ medium has been tested and proven to support robust growth of epithelial stem cells derived from human tissues or other mammals in the absence of the irradiate feeder of mouse fibroblast cells (3T3-J2).” paragraph [0494]). The Specification teaches that inclusion “ of jagged-1 and nicotinamide in the medium was observed to induce the abortion of some epithelial stem cell (lung, esophagus etc) self-renewal, and so the those two components are not used in present media” (para. [0494]). Furthermore, the Specification teaches that R-spondin was found not required to support the self-renewal and multipotency of stratified epithelial stem cells (para. [0494]). The Specification concludes that these two media have been used to passage “Epithelial stem cells from a variety of different tissues, including lung and Esophagus, have been passaged in the present medium for more than twenty-five passages and maintain self-renewal ability and multi-potent differentiation ability both in vitro and in xenograft model using NSG mice.” (para [0495]).
The claims as written do not require the specific reagents and concentrations as disclosed for the SQM Medium and SGM-63+ medium. The claims are broadly directed to a genus of defined culture media for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture. There is not structure/function correlation of the claimed defined culture media. The instant claims are drawn to a broad scope of a genus of potential defined culture media that would need to be tested in order to not only determine agents for the rapid isolation/cloning of stratified epithelial stem cells but also acceptable for in vivo treatment ([paragraph [0009]).
The prior art support specific reagents and concentrations in a culture medium for isolating a stem cell from epithelial tissue, preferably stratified epithelial tissue, and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture. Prior art of Zhang et al (Cell Rep . 2018 Oct 16;25(3):598-610; of record IDS filed 7/9/2024, discloses that the synergistic effect of inhibition of A83-01( a TGF-β inhibitor) and Y-27632(a PAK1-ROCK-Myosin II inhibitor), in low calcium conditions (e.g., EpiX medium), supports extended expansion of epithelial stem cells in 2D format (“we found that TGF-β signaling inhibitor (0.5–2 μM A83-01) and ROCK inhibitor (5–10 μM Y-27632) synergistically promoted epithelial cell proliferation (Figures 1B and S1)” ; page 4, para 1). Moreover, Zhang et al., discloses that when increasing C2+ above 1 mM, HFKs (Human Foreskin Keratinocytes) cultured at the air-liquid interface (ALI) matured into stratified epithelium after 2 weeks (page, 6, para 2; Figure 4F). Thus, the prior art supports specific reagents, concentrations in a culture medium, e.g, EpiX medium, and days of culture for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture concentration for synergistic effect.
The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose a full exemplary reagents in defined culture medium that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. The specification fails to provide any structural features coupled to the claimed functional characteristics (isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture). The instant specification fails to describe a representative number of defined culture media that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. Therefore, one could not readily envision members of the broadly claimed genus.
Given the lack of representative examples to support the full scope of the claimed defined culture medium used for isolating and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture, and lack of reasonable structure-function correlation with regards to the unknown structure, the present claims lack adequate written description.
Conclusion
Claims 1-7 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications should be directed to Supervisor Patent Examiner Maria G Leavitt whose telephone number is (571)272-1085. The examiner can normally be reached 8:30 am -5:30 pm.
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/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634