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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/18/2026 has been entered. Claims 17, 19, 22, 23, 29, 31 and 34-38 are amended.
Claims 17 and 29 are amended to recite “the functional derivative has the 5th cysteine of the sCD83 protein substituted by a serine”. The instant specification discloses at the paragraph bridging pages 17-18 that “it is preferred that one cysteine residue, more preferably the fifth cysteine residue, has been replaced…preferably the soluble CD83 protein comprises amino acid residues 20 to 144 of SEQ ID NO: 2, where the cysteine residue at position 129 has been replaced by a serine residue”, thus providing support for this limitation.
Claims 23 and 35 depend from claims 22 and 34, respectively. Claims 22 and 34 recite the sCD83 protein comprises amino acid residues 20-144 of SEQ ID NO: 2, where the cysteine residue at position 129 has been replaced by a serine residue, which is represented by the 125-residue sequence:
TPEVKVACSEDVDLPCTAPWDPQVPYTVSWVKLLEGGEERMETPQEDHLRGQHYHQKGQNGSFDAPNERPYSLKIRNTTSCNSGTYRCTLQDPDGQRNLSGKVILRVTGSPAQRKEETFKKYRAE.
Claims 23 and 35 recite that the sCD83 protein comprises amino residues 1-130 of SEQ ID NO: 10. An alignment between these two sequences is shown below:
RESULT 1
US-17-996-366B-10
Query Match 100.0%; Score 684; DB 1; Length 139;
Best Local Similarity 100.0%;
Matches 125; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPEVKVACSEDVDLPCTAPWDPQVPYTVSWVKLLEGGEERMETPQEDHLRGQHYHQKGQN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 14 TPEVKVACSEDVDLPCTAPWDPQVPYTVSWVKLLEGGEERMETPQEDHLRGQHYHQKGQN 73
Qy 61 GSFDAPNERPYSLKIRNTTSCNSGTYRCTLQDPDGQRNLSGKVILRVTGSPAQRKEETFK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 74 GSFDAPNERPYSLKIRNTTSCNSGTYRCTLQDPDGQRNLSGKVILRVTGSPAQRKEETFK 133
Qy 121 KYRAE 125
|||||
Db 134 KYRAE 138
The 130-residue sCD83 protein set forth in SEQ ID NO: 10 shares 100% sequence identity with residues 20-144 of SEQ ID NO: 2, where the cysteine residue at position 129 has been replace by a serine residue. Further, since SEQ ID NO: 10 comprises 5 extra residues, it properly limits the sequence recited in claims 22 and 34 because it provides greater detail, i.e., more amino acid residues.
Claims 17-24 and 27-38 are under examination.
Rejections Withdrawn
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
The rejection of claims 22-24 and 34-36 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is withdrawn in response to Applicant’s amendment of the claims. First, claims 22-23 and 34-36 are limited to soluble CD83 proteins comprising amino acid residues 20-144 of SEQ ID NO: 2 wherein the cysteine residue at position 129 is replaced by serine, amino acid residues 1-130 of SEQ ID NO: 10, or amino acids 8-133 or 1-133 of SEQ ID NO: 12. These limitations are encompassed by the examiner’s statement of enablement at p. 4 of the Office action mailed 02/24/2026. Second, claim 29, from which claims 34-36 depend, has been amended to delete reference to prevention, thus claim 34-36 no longer encompass prevention.
Claim Rejections - 35 USC § 112(a) – Written Description
The rejection of claims 34 and 35 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 in response to Applicant’s amendment. Specifically, claims 34 and 35 are limited to soluble CD83 proteins comprising amino acid residues 20-144 of SEQ ID NO: 2 wherein the cysteine residue at position 129 is replaced by serine and amino acid residues 1-130 of SEQ ID NO: 10.
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
The rejection of claims 17-21, 27-33, 37 and 38 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement, is maintained for reasons of record and the following. Applicant’s amendment of the claims to delete reference to prevention is acknowledged, and the issues raised with regard to prevention are overcome.
As noted in the previous Office actions mailed 10/15/2025 and 02/24/2026, the specification is enabling for the claimed methods comprising administering a soluble CD83 comprising:
amino acid residues 20-145 of SEQ ID NO: 2;
amino acid residues 1-130 of SEQ ID NO: 8;
amino acid residues 1-130 of SEQ ID NO: 10, or
amino acid residues 8-133 or 1-133 of SEQ ID NO 12.
The specification, does not, however, reasonably provide enablement for the claims as broadly recited. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claims encompass methods for inducing hair growth comprising administering a soluble CD83 (sCD83) protein, wherein the sCD83 protein may be a fragment (claims 17-24, 27, 28, 30, 37 and 38) or a functional derivative thereof (claims 17-21, 27-33, 37 and 38). Claims 17 and 29 have been amended to recite the functional derivative is non-glycosylated, and/or has the 5th cysteine of the sCD83 protein substituted by a serine, however, this only limits a single residue in the alternative. The specification discloses at p. 11, 2nd paragraph:
Suitable fragments are those having the same activity and conformation as natural CD83. Suitable derivatives of the sCD83 include proteins having up to 10 amino acids attached to the C- or N-terminus of the sCD83 protein and/or proteins having up to 10 amino acids, preferably one to five amino acids, of the sCD83 substituted.
While this passage suggests suitable derivatives may include “proteins having additional sequences attached to its C- or N-terminus, e.g. those carrying part of a transmembrane domain at their C-terminus or carrying at their N-terminus a short functional peptide (Gly-Ser-Pro-Gly)”, it also specifically states that such derivatives are not limited to those preferred embodiments. Regarding derivatives, the instant specification discloses further at p. 17, 2nd paragraph:
The sCD83 protein for use in the present invention also include[s] derivatives of soluble forms of members of the CD83 family of proteins according to the invention as mentioned above in which one or more amino acids has been added, deleted, substituted, inserted or inverted as long as these derivatives remain soluble as defined above and are capable of exhibiting a healing function. It also includes splice variants of the CD83 compounds mentioned hereinbefore.
In addition, the specification discloses that CD83 proteins may differ from the naturally occurring protein by up to 30% (see top of p. 12). Thus, the claims encompass a genus of variant sCD83 polypeptides, many of which are left to the skilled artisan to discover.
The instant specification provides evidence that sCD83 boosts hair growth in mouse models, including eyelashes (see pages 36-38). Further, the specification discloses that sCD83 as set forth amino acid residues 20-145 of SEQ ID NO: 2 is superior to an Fc-CD83 fusion protein (see p. 39). Applicant does not teach, however, how up to 30% of residues can be mutated in SEQ ID NO: 2 while maintaining the ability to promote hair growth, nor any functional derivatives or fragments capable of promoting hair growth. The post-filing date art discloses that the only sCD83 fragment/functional derivative capable of “pro-regenerative properties” is “the extracellular domain of CD83” (see p. 2, left column, 2nd full paragraph of Hollard et al., Wound Repair and Regeneration, 2026; 34:e70158 https://doi.org/10.1111/wrr.70158; 13 pages total).
The number of mutations generally possible in any given protein that can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g., such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. The art provides evidence that mutations can be destabilizing and their effects unpredictable. Bhattacharya et al. (PLoS ONE 12(3): e0171355. 2017; https://doi.org/10.1371/ journal.pone.0171355; 22 pages total—of record) teach even single nucleotide variations have a “range of effects at the protein level that are significantly greater than assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge” (p. 18, 1st and 2nd paragraphs). In addition, Fenton et al. (Medicinal Chemistry Research (2020) 29:1133-1146—of record) review the unpredictability of making substitutions at non-conserved positions in a protein, which can have significant effects on protein function that computational algorithms cannot predict very well (p. 1134, right column, middle paragraph).
Although machine learning algorithms have improved the ability to predict protein 3D structure from sequences, methods based on artificial intelligence for predicting the impact of mutations on protein stability still face challenges, including prediction biases towards “generalization”, “data set”, “destabilizing mutations” and the inability to predict the effects of multiple mutations. See Figure 1, at p. 162 and the discussion at pages 165-166 of Pucci et al. (Current Opinion in Structural Biology 2022, 72: 161-168—of record). Even in the case of single mutations, artificial intelligence programs do not accurately “predict the impact of mutation on protein stability” or function (see p. 2, 2nd paragraph and p. 7, 1st full paragraph of Pak et al., PLoS ONE 18(3): e0282689. 2023; https://doi.org/ 10.1371/ journal.pone.0282689—of record).
In the instant case, the claims encompass fragments and functional derivatives, but have provided little or no guidance beyond the mere presentation of sequence data to enable one of ordinary skill in the art to determine, without undue experimentation, the positions in the protein which are tolerant to change by amino acid substitutions or deletions, and the nature and extent of changes that can be made in these positions. Although the specification outlines art-recognized procedures for producing and screening for active muteins, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation.
Due to the large quantity of experimentation necessary to design and test sCD83 fragments and functional derivatives capable of promoting hair growth, the lack of direction/guidance presented in the specification regarding, and the absence of working examples directed to functional derivatives and fragments capable of carrying out the claimed methods, the complex nature of the invention, the unpredictability of the effects of mutation on protein structure and function, and the breadth of the claims which fail to recite limitations to the sCD83 polypeptides, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Response to Arguments
Applicant argues at pages 6-7 that the claims have been amended to recite enabled embodiments and states that the specification is enabling for non-glycosylated functional derivatives, the extracellular domain, of a CD83 protein, dimer or trimer forms of sCD83 comprising amino acids 20-144 of SEQ ID NO: 2, and monomeric sCD83 proteins having SEQ ID NO: 20-144 of SEQ ID NO: 2.
This argument has been fully considered, but is not found persuasive. As noted in the statement of the rejection, the examiner takes no issue with the enabled embodiments. The issue raised herein concerns the undefined “fragments” and “functional derivatives” of those enabled embodiments. Neither Applicant’s amendment nor the arguments address this issue.
Written Description
The rejection of claims 17-21, 27-33, 37 and 38 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 maintained for reasons of record and the following. The claims encompass methods for inducing hair growth comprising administering a soluble CD83 (sCD83) protein, fragments or functional derivatives thereof. Claims 17 and 29 have been amended to recite the functional derivative is non-glycosylated, and/or has the 5th cysteine of the sCD83 protein substituted by a serine, however, this only limits a single residue in the alternative. The specification discloses at p. 11, 2nd paragraph:
Suitable fragments are those having the same activity and conformation as natural CD83. Suitable derivatives of the sCD83 include proteins having up to 10 amino acids attached to the C- or N-terminus of the sCD83 protein and/or proteins having up to 10 amino acids, preferably one to five amino acids, of the sCD83 substituted.
While this passage suggests suitable derivatives may include “proteins having additional sequences attached to its C- or N-terminus, e.g. those carrying part of a transmembrane domain at their C-terminus or carrying at their N-terminus a short functional peptide (Gly-Ser-Pro-Gly)”, it also specifically states that such derivatives are not limited to those preferred embodiments. Regarding derivatives, the instant specification discloses further at p. 17, 2nd paragraph:
The sCD83 protein for use in the present invention also include[s] derivatives of soluble forms of members of the CD83 family of proteins according to the invention as mentioned above in which one or more amino acids has been added, deleted, substituted, inserted or inverted as long as these derivatives remain soluble as defined above and are capable of exhibiting a healing function. It also includes splice variants of the CD83 compounds mentioned hereinbefore.
In addition, the specification discloses that CD83 proteins may differ from the naturally occurring protein by up to 30% (see top of p. 12). Thus, the claims encompass a genus of undisclosed sCD83 functional derivatives and fragments that require the function of inducing hair growth.
The MPEP 2163(A) states “‘[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.’” For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. (See MPEP 2163(II)(A)(3)(a)(i)). In deciding whether the application complies with the written description requirement of 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant is claiming (see previous paragraph) and what Applicant has possession of. From the specification, it is clear that Applicant has possession of an sCD83 having amino acid residues 20-145 of SEQ ID NO: 2; amino acid residues 1-130 of SEQ ID NO: 8 or 10 and amino acid residues 8-133 or 1-133 of SEQ ID NO: 12.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the claims is the recitation of functional derivatives and fragments. The disclosure of four species is not representative of the genus of sCD83 functional derivatives and fragments encompassed by the claims. The specification does not disclose how the sCD83 polypeptides can be mutated and still retain their ability to promote hair growth. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). With the exception an sCD83 having amino acid residues 20-145 of SEQ ID NO: 2; amino acid residues 1-130 of SEQ ID NOs: 8 or 10 and amino acid residues 8-133 or 1-133 of SEQ ID NO: 12, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. 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. Therefore, only isolated polypeptides comprising an sCD83 having amino acid residues 20-145 of SEQ ID NO: 2; amino acid residues 1-130 of SEQ ID NOs: 8 or 10 and amino acid residues 8-133 or 1-133 of SEQ ID NO: 12, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Response to Arguments
Applicant argues at p. 8 of the Remarks filed 05/18/2026 that “to satisfy the written description requirement, ‘the applicant does not have to utilize any particular form of disclosure to describe the subject matter claimed, but the description must clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’, citing Carnegie Mellon Univ. v. Hoffman-La Roche Inc., 541 F.3d 1115, 1122 (Fed. Cir. 2008) and Vas-Cath Inc. v. Mahurka, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). Applicant asserts the as-filed application describes the subject-matter of the claims in a manner that clearly allows one skilled in the art to recognize that Applicant invented what is claimed, citing pages 7-8, 10, 20 and 36-38 of the instant specification and providing experimental data on hair growth induction by systemic and/or topical administration of said sCD83.
This argument has been fully considered, but is not found persuasive. The claims also recite functional derivatives and fragments. The specification does not disclose how the sCD83 polypeptides can be mutated and still retain their ability to promote hair growth. A comparison of sequences set forth in SEQ ID NOs: 8, 10 and 12 shows that they only differ by a single substitution, which is not representative of the genus of undisclosed functional derivatives and fragments that must retain the ability to promote hair growth.
New Objections
Claim Objections
Claims 22-24 and 34-36 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 17, 20, 29 and 32 objected to because of the following informalities. The claims recite “5th” (claims 17 and 29) and “fifth” (claims 20 and 32) when referring to the cysteine residue. For the sake of parallel structure and consistency, either “5th” or “fifth” should be used throughout the claims.
Appropriate correction is required.
Conclusion
Claims 17-21, 27-33, 37 and 38 are rejected and claims 22-24 and 34-36 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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