Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 24, 2026, has been entered.
DETAILED ACTION
Applicant’s response filed February 24, 2026, has been considered. Rejections and/or objections not reiterated from the previous office action mailed March 24, 2025, are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The amended claims filed on February 24, 2026, have been acknowledged. Claims 2, 4-5, and 14 were cancelled. Claims 1 and 11 were amended. Claims 15-16 are new. Claims 1, 3, 6-13, and 15-16 are pending and examined on the merits.
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d).The applicant claims foreign priority from JP2018-179816 filed on September 26, 2018. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, received March 26, 2021. While a certified copy of the foreign patent application JP2018-179816 is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, 6-7, 10-13, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 20070212335 (Hantash) and further in view of United States Patent Application No. 20090198336 (Qiao) and Ma et al. (Journal of Investigative Dermatology 137: 1015-1024. 2017). This is a new rejection made in response to Applicant’s amendments to the claims. Applicant’s traversal has been fully considered but is moot in response to the new rejection of record.
Regarding claim 1, Hantash teaches a method of generating hair follicle germ cells by implanting hair follicle stem cells and a scaffold into the base of microchannel pores created in excised human skin samples. The stem cells attach to the scaffold and the dermis. Hair follicle placod formation is promoted by using serum free media (such as DMEM/F12 (identified as a suitable basal media in paragraph 0029 of the specification)) containing FGF (FGF2 and FGF4) and noggin treatment is continued for 2-3 days until the stem cells populate the microchannel pore and sprout a bud. After the hair follicle bud has sprouted within the base of the cavitary lesion created by the laser injury of scalp or skin, stem cells continue to proliferate over the following 1 to 21 days leading to the development of hair follicle germ and finally a hair follicle peg (paragraphs 0037-0056, Examples 1-2, and Figure 12).
Hantash teaches that compositions comprising one or more stem cells, a differentiation factor, and a scaffold, can comprise stem cells derived from the hair follicle bulge (i.e. epithelial stem cells) (paragraphs 0027-0028).
The stem cells described above, such as the expanded hair follicle stem cells, can be used for a variety of purposes, including, but not limited, to hair transplant therapy, such as transplantation of hair follicles or skin grafts containing transplanted stem cells into the scalp or skin (paragraph 0052).
Hantash does not teach wherein the SHH agonist SAG is included in the media.
However, Qiao teaches a culture media for promoting proto-hair development in vitro for implantation in vivo to produce a mature hair follicle. Qiao teaches that the media can comprise FGF, shh agonists, and BMP inhibitors (paragraphs 0005-0007 and 0110-0112).
Qiao is silent as to which shh agonists can be included.
Ma teaches that the shh agonist SAG is known to cause hair regeneration in depilated mice when topically applied to the skin (Figure 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the hair regeneration solution of Hantash with the shh agonist SAG, as identified by Qiao and Ma, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Hantash and Qiao are both focused on using solutions comprising dermal papillae stem cells to regenerate hair follicles and to transfer the regenerated hair follicle to a patient. Furthermore, Ma shows that SAG is known to improve hair regrowth when used in vivo. Additionally, Hantash has already identified Sonic hedgehog (shh) as being an important inducer of the hair follicle placode (paragraph 0055). As such, it would have been obvious to combine them into a single media to improve the rate of hair regrowth. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Furthermore MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
Regarding the in vitro culture, Hantash, as stated supra, teaches that hair follicle placod formation is promoted by using serum free media containing FGF (FGF2 and FGF4) and noggin treatment for 2-3 days until the stem cells populate the microchannel pore and sprout a bud. After the hair follicle bud has sprouted within the base of the cavitary lesion created by the laser injury of scalp or skin, stem cells continue to proliferate over the following 1 to 21 days leading to the development of hair follicle germ and finally a hair follicle peg (paragraphs 0037-0056, Examples 1-2, and Figure 12). Furthermore, Hantash teaches that hair follicle stem cells can be cultured in suspension or on a fixed substrate. The hair follicle stem cells are grown on tissue culture plates, and can be cultured at high cell density to promote the suppression of
asymmetric cell kinetics. Conditions for culturing should be close to physiological conditions. The pH of the culture medium should be close to physiological pH. Physiological temperatures range between about 30° C. to 40° C. Therefore, it would be well understood that the excised skin comprising the hair follicle stem cells could be cultured in a dish in order to incubate it at physiological temperatures while maintaining a sterile environment before transplantation.
Regarding claim 3, Hantash, as stated supra, teaches that the stem cells are then treated with a serum free media (a basal media) containing FGF2, FGF4, and noggin.
Regarding claims 6-7, Hantash teaches that the media can further comprise EGF in combination with FGF2, FGF4, and noggin (claims 14-17).
Regarding claim 10, Hantash teaches that the media is serum free and comprises FGF4, FGF2, and Noggin. As such, there is no WNT or Notch antagonists in the media.
Regarding claim 11, Hantash teaches a method of generating hair follicle germ cells by implanting hair follicle stem cells and a scaffold into the base of microchannel pores created in excised human skin samples. The stem cells attach to the scaffold and the dermis. Hair follicle placod formation is promoted by using serum free media (such as DMEM/F12 (identified as a suitable basal media in paragraph 0029 of the specification)) containing FGF (FGF2 and FGF4) and noggin treatment is continued for 2-3 days until the stem cells populate the microchannel pore and sprout a bud. After the hair follicle bud has sprouted within the base of the cavitary lesion created by the laser injury of scalp or skin, stem cells continue to proliferate over the following 1 to 21 days leading to the development of hair follicle germ and finally a hair follicle peg. Finally, anagen can be initiated by the replacement of the media with a serum free media containing FGF7. This allows the hair to begin to grow and cycle similar to a normal hair (i.e. trichogenic) (paragraphs 0037-0056, Examples 1-2, and Figure 12).
Hantash teaches that compositions comprising one or more stem cells, a differentiation factor, and a scaffold, can comprise stem cells derived from the hair follicle bulge (i.e. epithelial stem cells) (paragraphs 0027-0028).
The stem cells described above, such as the expanded hair follicle stem cells, can be used for a variety of purposes, including, but not limited, to hair transplant therapy, such as transplantation of hair follicles or skin grafts containing transplanted stem cells into the scalp or skin (paragraph 0052).
Hantash does not teach wherein the SHH agonist SAG is included in the media.
However, Qiao teaches a culture media for promoting proto-hair development in vitro for implantation in vivo to produce a mature hair follicle. Qiao teaches that the media can comprise FGF, shh agonists, and BMP inhibitors (paragraphs 0005-0007 and 0110-0112).
Qiao is silent as to which shh agonists can be included.
Ma teaches that the shh agonist SAG is known to cause hair regeneration in depilated mice when topically applied to the skin (Figure 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the hair regeneration solution of Hantash with the shh agonist SAG, as identified by Qiao and Ma, as part of the method of generating regenerated hair follicle germs of Hantash to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Hantash and Qiao are both focused on methods of generating regenerated hair follicle germs for transfer to a patient using solutions comprising dermal papillae stem cells to regenerate hair follicles. Furthermore, Ma shows that SAG is known to improve hair regrowth when used in vivo. Additionally, Hantash has already identified Sonic hedgehog (shh) as being an important inducer of the hair follicle placode (paragraph 0055). As such, it would have been obvious to combine them into a single media to improve the rate of hair regrowth as part of the method of generating regenerated hair follicle germs of Hantash. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the in vitro culture, Hantash, as stated supra, teaches that hair follicle placod formation is promoted by using serum free media containing FGF (FGF2 and FGF4) and noggin treatment for 2-3 days until the stem cells populate the microchannel pore and sprout a bud. After the hair follicle bud has sprouted within the base of the cavitary lesion created by the laser injury of scalp or skin, stem cells continue to proliferate over the following 1 to 21 days leading to the development of hair follicle germ and finally a hair follicle peg (paragraphs 0037-0056, Examples 1-2, and Figure 12). Furthermore, Hantash teaches that hair follicle stem cells can be cultured in suspension or on a fixed substrate. The hair follicle stem cells are grown on tissue culture plates, and can be cultured at high cell density to promote the suppression of
asymmetric cell kinetics. Conditions for culturing should be close to physiological conditions. The pH of the culture medium should be close to physiological pH. Physiological temperatures range between about 30° C. to 40° C. Therefore, it would be well understood that the excised skin comprising the hair follicle stem cells could be cultured in a dish in order to incubate it at physiological temperatures while maintaining a sterile environment before transplantation.
Regarding claim 12, Hantash teaches that collagenase can be used to dissociate stem cells from a collected donor skin or scalp tissue sample into single cells (paragraphs 0030 and 0036).
Regarding claim 13, Hantash teaches that the stem cells can be derived from the hair bulge region of the follicle (paragraphs 0028 and 0054).
Regarding claims 15-16, Hantash teaches that the media can further comprise EGF in combination with FGF2, FGF4, and noggin (claims 14-17).
Claims 1 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 20070212335 (Hantash) and further in view of United States Patent Application No. 20090198336 (Qiao) and Ma et al. (Journal of Investigative Dermatology 137: 1015-1024. 2017) as applied to claim 1 above and further in view of Lee et al. (Cell Reports 22. 242-254. 2018). This is a new rejection made in response to Applicant’s amendments to the claims.
The teachings of Hantash, Qiao, and Ma are as discussed above.
The combined teachings of Hantash, Qiao, and Ma do not teach wherein the ALK5 inhibitor SB431542 is included in the media.
However, Lee teaches a culture media for promoting hair follicle formation from pluripotent stem cells. Lee teaches that they treated the cells on day 3 with SB431542 and BMP to induce surface ectoderm, followed by day 4 treatment with FGF-2 and LDN-193189 to induce placodal epithelium. The percentage of cells generating 15 or more HFs was significantly greater under the SB/BMP-FGF/LDN full-treatment condition compared to SB/BMP-LDN conditions. As identified in the methods, SB431542 remains in the media upon addition of FGF-2 and LDN-193189 (a BMP inhibitor) (page 242, column 2, paragraph 2-page 246, column 1, paragraph 2, page 252, column 2, paragraph 2, and Figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the hair regeneration solution of Hantash, Qiao, and Ma with the ALK5 inhibitor SB431542, as identified by Lee, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Hantash, Qiao, and Lee are both focused on using solutions comprising stem cells to regenerate hair follicles. Furthermore, Lee shows that the percentage of cells generating 15 or more HFs was significantly greater under the SB/BMP-FGF/LDN full-treatment condition compared to SB/BMP-LDN conditions. Therefore, Lee shows that combining SB431542 with FGF-2 and a BMP inhibitor, as is done by Hantash, improves hair regeneration. As such, it would have been obvious to combine them into a single media to improve the rate of hair regeneration. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Furthermore MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
Conclusion
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/KEENAN A BATES/Examiner, Art Unit 1631
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