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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8 in the reply filed on 04/02/2026 is acknowledged.
Claims 9-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/02/2026.
Specification
The disclosure is objected to because of the following informalities: The Specification, at page 11 discusses Figures 2 and 3 as depicting hair follicles obtained by each of the method of the present invention and by conventional methods. However, the figure descriptions at page 7 state that the follicles are only from Control Experiment 1, which are only conventional methods. Clarification or appropriate correction is required.
Claim Objections
Claims 1-8 are objected to because of the following informalities: The claims general are written with unconventional grammar. I can be discerned what is intended in most instances but Applicant is encourage to amend the claims. Some examples are set forth in the section addressing claim clarity, below. Appropriate correction is required.
Drawings
The drawings are objected to because they are of poor resolution/quality. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1,2 and 4-8 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.
*Note-Claim 3 is not included in this rejection as the enzyme solution is limited to a dispase/collagenase solution.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).”
In the instant case the claimed digestive enzyme solutions encompassed by the claims lack a written description. The specification teaches only a 1:1 mixture of dispase and collagenase encompassed by the genus and it was unknown as of Applicants’ effective filing date that any other known mixture of enzymes would have the same properties as a 1:1 dispase:collagenase mixture when used on human scalp tissue under the claimed conditions. The Specification and art teach that the hair follicle condition and cellular composition can vary based on dissociation conditions and the characteristics of the enzymes used.
The phrase “digestive enzyme mixture” broadly encompasses any mixture and ratio of digestive enzymes. Possession of the claims requires the possession of a representative number the genus of all enzyme combinations that have the corresponding feature of dissociating hair follicles that comprise the same cellular composition as the enzyme combination supported by the specification.
The invention relates to tissue digestion conditions to obtain a human hair follicle single cell suspension. Human scalp hair follicles are rich in melanocytes, which are useful intreating vitiligo. The follicles also contain keratinocytes and stem cells that are useful in other methods. Methods of isolating the follicles can alter the presence or amounts of the cells obtained.
The claims are drawn to a method of dissociating human scalp tissue into a single cell suspension of scalp hair follicle cells. The claims recite use of a digestive enzyme solution but do not limit the enzymes included in the solution.
The Specification and art discuss how digestion conditions can greatly affect the integrity and composition of hair follicles when dissociating them from scalp tissue. Various enzymes have been used in a variety of methods to obtain hair follicle single cell suspension. Scalp tissue comprises a dermal and epidermal layer and the hair follicles are embedded in the epidermal layer. The follicles can be obtained by separating the dermis from the epidermis then dissociating the follicle from the surrounding epidermis. Enzymes used in dissociation have included dispase, trypsin and thermolysin. Gragnani (Braz. J. Biol., 67(1): 105-109, 2007) teaches that trypsin separates supra basal hemidesmossomes and leaves basal layer cells attached to dermal pieces while thermolysin is able to separate the tissue at the basal membrane zone by targeting dermal-epidermal junctions and leads to a cleaner separation of dermal and epidermal layers (see also Cattier, Int. J. Mol. Sci. 2025, 26, 1852, 18 pages and Walzer, THE JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol. 92. No. 1, 1989). Cattier discusses that use of thermolysin “allows for the preservation of stem cells while minimizing fibroblast contamination in the cultures, offering a higher quality and quantity of cells” (page 3). Thus, the different enzymes, by breaking different intercellular junctions, alters to composition of the final follicle single-cell suspension. Figure 2 of Cattier presents a flowchart of different approaches to follicle cell isolation including comparison to trypsin vs a two-step thermolysin process to separate layers then dissociate the follicles from the scalp.
The specification compares “conventional methods” of dissociation which include an overnight treatment with 0.5% dispase followed by 0.5% collagenase before separating out the hair follicles. The methods of the instant invention use a small range of concentrations of 1:1 dispase:collagenase for varying short periods of time (30-90 min) at low temperature followed by a second short period at 30-37 degrees C to obtain follicles, then the follicles are dissociated into single cells with pancreatin-EDTA. The Specification shows that the follicles obtained with the 1:1 dispase:collagenase lead to isolation of complete follicles with a full bulge area (where useful epithelial stem cells are located) with the cells at the root being complete. Conventional methods, on the other hand, lose cells at the hair root (see page 11 and Figures 2-3).
The Specification teaches 1:1 dispase:collagenase for follicle isolation and does not mention any other digestive enzyme encompassed by the genus. Therefore, the art and specification-supported variabilities in the effects of different enzymes in follicle isolation, it is reasonable to conclude that Applicant did not possess full breadth of the claimed invention.
With the exception of an enzyme solution that is 1:1 dispase:collagenase. the skilled artisan cannot envision the detailed chemical structure of the encompassed enzyme solution, and therefore conception is not achieved regardless of the complexity or simplicity of the method of isolation.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that “to fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
Claim Rejections - 35 USC § 112
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 1-8 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 1 is unclear at step 2. It is not clear if step 2 is intended to contain a step of physically removing the dissociated hair follicles from the surrounding tissue prior to step 3. The resulting cell composition following step 3 will differ depending on whether the dissociated follicle is removed and digested without surrounding epidermis. Claims 2-8 are unclear given their dependency from and failure to clarify claim 1.
Claim 2 is unclear in reference to “a treatment time” for claim 1, step 1 because there is only a single treatment time. Reciting “the treatment time” would be remedial.
Claim 3 is unclear at lines 2-3, stating “the digestive enzyme solution is prepared”. This phrase is referring to claim 1, steps 1 and 2, which do not have a step of preparing the enzyme solution. This phrase would be clear if it read “wherein the digestive enzyme solution was prepared by…”
Claim 6 is unclear in reciting “too much”. The metes and bounds of “too much” are not clear. The phrase “a volume of the pre-cooled…solution is subject to completely submerge…” is unclear because it cannot be discerned what Applicant is trying to claim. Similarly, the phrase “standing the pre-cooled 0.5-1.5% digestive enzyme solution submerging the …tissue is wholly unclear.
Claim 6 is unclear if it is adding a step to step 1 of claim 1 or if it is limiting the step 1 of claim 1.
Claim 7 is unclear if it is adding a step to step 2 of claim 1 or if it is limiting the step 2 of claim 1. The phrase “digesting the digestive enzyme solution” is unclear as the enzyme solution is present to digest tissue. Finally it is not clear if the transfer to a culture dish to dissociate the hair follicles is a second dissociation as the follicles are dissociated in claim 1, step 2.
Claim 8 is unclear in reference to “a treatment time” for claim 1, step 1 because there is only a single treatment time. Reciting “the treatment time” would be remedial.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. CN110859855 is in the same field of endeavor and teaches a single dissociation step, placing skin in dispase overnight at 4 degrees C followed by use of pancreatin at 37 degrees C to digest and obtain single cells from the follicles.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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