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
Response to Election/Restriction filed on December 12, 2025 is acknowledged. Claims 16-17 were canceled, 1-3, 5 and 19 were amended, claim 22 was newly added and 1-15, 18-22 are pending in the instant application.
Election/Restrictions
Applicant elected with traverse Group 1 (claims 1-7, 19) drawn to a composition and with traverse pharmaceutical composition with a single enzyme group, gel formulations and hidradenitis suppurativa in the reply filed December 12, 2025. Applicant argues that Sorensen does not disclose compositions as claimed in the present application since the compositions of Sorensen are highly unstable for topical application to human skin. Applicant’s arguments have been fully considered but not found persuasive. Wells (see reference and teachings below) teaches a topical formulation comprising endoproteinase Glu-C is V8 protease from S. aureus (see table 2) which as evidenced by Uniprot (see attached handout, protein Accession P0C1U8, see sequence and Alternative names) comprises instant SEQ ID NO:14 and thus, breaks unity of invention. Thus, the technical feature is taught by Wells as evidenced by Uniprot and thus, inventions 1-2 lack unity of invention.
The restriction is deemed proper and is made FINAL in this office action. Claims 6-15, 18, 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-5, 19 and 22 are examined on the merits of this office action.
Claim Objections
Claim 1 is objected to for the following informality: the limitation of “a glutamyl endopeptidase” in line 11 should be replaced with -wherein glutamyl endopeptidase is defined as…-
Claim 1 is further objected to for the following reasons: Claim 1 claims amino acid sequences (AAPE, EEPA, AAPD etc…). The peptide sequences are missing the sequence identifier. The proper way to claim a peptide sequence is for example, AAPE (SEQ ID NO: X) (see 37 CFR 1.821(d)). This error should be corrected.
Furthermore, the periods after “a” and “b” should be removed from instant claim 1 as periods should only be included at the end of the claim (see MPEP 608.01(m)). Periods may not be used elsewhere in the claims except for abbreviations.
Sequence Compliance-Specification and Claim Objection
This application fails to comply with the requirements of 37 C.F.R 1.821-1.825 for the reasons set forth on the attached Notice to Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821-1.825) before the application can be examined under 35 U.S.C 131 and 132. Each sequence disclosed must appear separately in the “Sequence Listing.” Each sequence set forth in the “Sequence Listing” must be assigned a separate sequence identifier. Applicant failed provide sequence identifiers for all sequences listed in claims. For example, the 4mer peptides in instant claim 1 (and throughout the specification, for example see page 28) require sequence listings.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 19, 22 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, Claims 1-5, 19, 22 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below and is based on MPEP2106.03-MPEP2106.05.
Claim Interpretation
Claim 1 claims “A composition which is pharmaceutically acceptable for topical application to human skin, comprising one or more enzymes, where the composition is: a). a pharmaceutical composition, comprising at least one pharmaceutically acceptable ingredient in addition to the one or more enzymes; or b) a cosmetic composition, comprising at least one cosmetically acceptable ingredient in addition to the one or more enzymes, wherein the one or more enzymes are selected from glutamyl endopeptidases; wherein a glutamyl endopeptidase is defined as an endopeptidase exhibiting a glutamyl endopeptidase ratio (GR) > 5, where GR is calculated as the enzyme activity exerted by the endopeptidase on substrate Suc-AAPE-pNA divided by the highest of activities exerted by the endopeptidase on substrates Suc- AAPA-pNA, Suc-AAPD-pNA, Suc-AAPF-pNA, Suc-AAPI-pNA, Suc-AAPK-pNA, Suc-AAPL-pNA,Suc-AAPM-pNA, Suc-AAPR-pNA, and Suc-AAPV-pNA.”. Claims 2-3 further define endopeptidases of the invention comprising SEQ ID Nos1, 12-14 or variants thereof. Claim 5 claims wherein the composition is able to promote delivery of enzyme to the site of actuation …formulated as a gel…cream liquid…etc…”
Subject Matter Eligibility Test for Products and Processes
Step 1: Is the claim to a process, machine, manufacture, or composition of matter (see MPEP
2106.03)?
Yes, the instant claims are directed to a statutory patent-eligible subject matter category, namely a composition of matter.
Step 2A (1): Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea
(see 2106.04)?
Yes, the claims are directed to a natural phenomenon, namely a naturally-occurring enzymes. For example, instant SEQ ID NO:14 is Glutamyl endopeptidase from staphylococcus aureus (see attached handout, Uniprot Protein database P0C1U8). As evidenced by Applicant’s specification, instant SEQ ID NO:1, 12-14 (table 3) are all naturally occurring and inherently would have the claimed activity ratio (see Table 4). SEQ ID NO:1 is also naturally occurring (see Tables 1-2).
Accordingly, the pending claims are directed to naturally occurring proteolytic enzymes.
As the product is found in nature, consideration is given to whether it is integrated into a practical application or contains other elements that provide a marked difference as compared to the natural counterpart.
Step 2A (2): Does the Claim recite additional Elements that integrate the judicial Exception into a Practical Application? (see MPEP 2106.04 (d)) NO. This judicial exception is not integrated into a practical application because it does not provide a treatment that affirmatively recites an action that effects a particular treatment for a disease or medical condition.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception (see MPEP 2106.05))?
No, the claim does not recite additional elements that amount to significantly more than the judicial exception, as explained below. Factors for determining if the claim directed to a product of nature, as a whole, recites something significantly more than the judicial exception, are provided in MPEP 2106. Instant claims 1 and 5 are drawn to a pharmaceutical/cosmetic formulations including liquids to be applied topically to human skin. Given the broadest reasonable interpretation, this could be water in combination with the enzyme which is naturally occurring and there is no evidence that the combination of the peptide and water results in a different property or function of the peptide. The peptide of the instant claims (and in combination with water or another naturally occurring excipient) does not amount to significantly more than the exception.
In sum, when the relevant considerations are analyzed, they weigh against a significant difference. Accordingly, Claims 1-5, 19 and 22 do not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112, First Paragraph
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 1-5, 19, 22 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.
MPEP § 2163 states that 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, 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.
Scope of the claims
Claim 1 claims “A composition which is pharmaceutically acceptable for topical application to human skin, comprising one or more enzymes, where the composition is: a). a pharmaceutical composition, comprising at least one pharmaceutically acceptable ingredient in addition to the one or more enzymes; or b) a cosmetic composition, comprising at least one cosmetically acceptable ingredient in addition to the one or more enzymes, wherein the one or more enzymes are selected from glutamyl endopeptidases; wherein a glutamyl endopeptidase is defined as an endopeptidase exhibiting a glutamyl endopeptidase ratio (GR) > 5, where GR is calculated as the enzyme activity exerted by the endopeptidase on substrate Suc-AAPE-pNA divided by the highest of activities exerted by the endopeptidase on substrates Suc- AAPA-pNA, Suc-AAPD-pNA, Suc-AAPF-pNA, Suc-AAPI-pNA, Suc-AAPK-pNA, Suc-AAPL-pNA,Suc-AAPM-pNA, Suc-AAPR-pNA, and Suc-AAPV-pNA.”. Claims 2-3 further define endopeptidases of the invention comprising SEQ ID NO:14 or variants thereof. Claim 5 claims wherein the composition is able to promote delivery of enzyme to the site of actuation …formulated as a gel…cream liquid…etc…”
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Thus, the claims define the genus primarily by functional activity given it encompasses any glutamyl endopeptidase having a GR>5 without limitation as to the amino acid sequence, structural features, subclass or source organism. Claims 2-3, 19 and 22 encompasses glutamyl endopeptidases having at least 80, 90, 95% sequence identity to SEQ ID Nos:1, 12-14 and or variants thereof with up to 10 substitutions. The possibilities are vast for both any glutamyl endopeptidase having a GR>5 and peptides having at least 80% sequence identity to EQ ID Nos:1, 12-14.
Actual Reduction to Practice
MPEP § 2163 states that 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification discloses experimental data involving a panel of approximately 14 endopeptidases (tables 1 and 3). The specification has functional assays relating to hair release (Example 1), force reduction (Example 3); stability (Example 4), skin protein hydrolysis (example 5) and additional mechanistic and delivery studies (Examples 6-10). From these experiments, only a limited subset of enzymes (HZ-2, HZ-10, HZ-13, HZ-15, HZ-35) demonstrate some level of relevant activity with HZ-2 (SEQ ID NO:1) consistently identified as most effective. There are no variants as encompassed by the claim of instant SEQ ID Nos:1, 12-14. The disclosure evidences reduction to practice of only a small number of specific species, rather than the full claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that 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, 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 thereof.
The specification does not provide sufficient identifying characteristics because the genus is primarily by functional performance (GR>5). Furthermore, the specification does not identify conserved sequence motifs, domains or structural features shared across the claimed enzymes. The disclosed enzymes originate from diverse organisms and protease classes with no unifying structural description. Thus, one of ordinary skill in the art would not be able to determine based on the specification, which enzymes fall within the claimed genus without undue experimentation.
Physical/Chemical Properties
The specification provides limited information regarding enzyme activity on peptide substrates, stability under certain conditions. However, the physical and chemical properties of the disclosed enzymes are show to be highly variable. The stability differs significantly among tested enzymes (see Example 4) and Enzymes exhibit different substrate specificities and hydrolysis profiles (Table 5, Example 5). The specification does not establish that the claimed genus shares common physical or chemical properties that correlated with the claimed function.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The claims rely heavily on function characteristics and in particular, glutamyl endopeptidase activity (GR>5). However, the specification fails to establish a predictive correlation between structure and function because enzymes with similar classifications exhibit divergent functional outcomes (see for example Examples 3-5). Some enzymes are overactive (non-specific), underactive or unstable under relevant conditions. The GR parameter does not reliably predict hair release efficacy, stability, selectivity or follicular delivery capability. Accordingly, the claimed functional limitation does not define a cohesive or predictable class of enzyme.
Method of Making
While the specification references known enzymes and purification techniques, it does not provide guidance sufficient to support the full scope of the claimed genus because it does not teach how to identify or generate new enzymes within the claimed genus. The specification does not provide methods for producing variants across the full scope of claimed sequence identify ranges and does not enable prediction of which variants will retain the claimed functional properties. Thus, the disclosure does not support possession of the full range of enzymes encompassed by the claims.
Conclusion
In conclusion, the claims encompass a broad, functionally defined genus of glutamyl endopeptidases. The specification discloses only a limited number of species. The experimental data demonstrate significant variability and unpredictability across the genus. The specification fails to provide sufficient representative species or structural features that correlate with the claimed function. Accordingly, the specification does not reasonably convey to one of ordinary skill in the art that the inventors were in possession of the full scope of enzymes having a GR>5 or the full scope of sequence variants encompassed by claims 2-3, 19 and 22. Therefore, claims 1-5 and 19, 22 are rejected under 35 U.S.C. 112(a) for lack of written description.
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.
Claim 5 is 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 5 recites “…delivery of enzyme”, whereas claim 1 recites “one or more enzymes”. It is unclear whether “enzyme” refers to a single enzyme, one of the previously recited enzymes or all of the previously recited enzymes. Accordingly, the term “of enzyme” lacks proper antecedent basis and renders the scope of the claim unclear. A suggested amendment would be “promotes delivery of the one or more enzyme…”.
Claim 5 further recites formulations using the phrase “such as” (e.g. “gel, cream such as semisolid emulsions…”). The phrase “such as” introduces non-limiting, exemplary language that fails to clearly define the scope of the claims because it is unclear whether the listed items are required or merely examples of a broader undefined category. As a result, one of ordinary skill in the art cannot determine the metes and bounds of the claim with reasonable certainty. Furthermore, while the term “including” is generally open ended, in the present claims its usage renders the scope unclear because it introduces an extensive and heterogenous list of items (e.g. gels, creams, emulsions, microneedles, patches, implants, injectable forms). The claim does not make clear whether these items are required, optional embodiments or merely illustrative examples of broader categories. As a result, the boundaries of the claimed composition are not reasonably certain.
The claim recites that the composition is “formulated as a…derma roller with microneedles, compressed air pressure, solid skin implant…” This language is unclear because a composition cannot be “formulated as” a device (e.g. derma roller, implant) or a delivery mechanism (e.g. compressed air pressure). The claim therefore mixes different statutory classes without defining their relationship. Accordingly, it is unclear whether the claim is directed to a composition, a device, or a method of delivery, and the scope of the claim cannot be determined with reasonable certainty.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-3, 5, 19 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wells (US20150175940 A1) as evidenced by Uniprot (protein Accession P0C1U8, see attached handout).
Wells teaches a formulation for use topically (claims 17-18) comprising endoproteinase Glu-C (see claim 3). Wells teaches wherein the endoproteinase Glu-C is V8 protease from S. aureus (see table 2) which as evidenced by Uniprot (see attached handout, protein Accession P0C1U8, see sequence and Alternative names) comprises instant SEQ ID NO:14. Regarding claims 1 and 5, Wells teaches for use topically in humans (see paragraph 0099). Well teaches incorporation into a gel, lotion, cosmetic (claim 16) thus meeting the limitations of at least one pharmaceutically or cosmetic acceptable ingredient in instant claim 1. Regarding the limitations of “endopeptidase exhibiting a glutamyl endopeptidase ratio (GR) > 5, where GR is calculated as the enzyme activity exerted by the endopeptidase on substrate Suc-AAPE-pNA divided by the highest of activities exerted by the endopeptidase on substrates Suc- AAPA-pNA, Suc-AAPD-pNA, Suc-AAPF-pNA, Suc-AAPI-pNA, Suc-AAPK-pNA, Suc-AAPL-pNA,Suc-AAPM-pNA, Suc-AAPR-pNA, and Suc-AAPV-pNA”, the peptide of Wells is identical to instant SEQ ID NO:14 (which is claimed in instant claims 2-3, 19 and 22) and thus, would inherently have the claimed property of a GR>5. This is further evidenced by Applicant’s own specification that shows specific activity for SEQ ID NO:14. Regarding claims 2-3, 19 and 22, Wells teaches wherein the endoproteinase Glu-C is V8 protease from S. aureus (see table 2) which as evidenced by Uniprot (see attached handout, protein Accession P0C1U8, see sequence and Alternative names) comprises instant SEQ ID NO:14.
Claim(s) 1-5, 19 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar (WO2008088472 A1) as evidenced by Uniprot (protein Accession P80057, see attached handout).
Kumar teaches a formulation for use topically (paragraph 0078) comprising at least one proteolytic enzyme, wherein the enzyme is Endo-Glu with a protein accession of P80057 (see paragraph 0089, claim 4) which is identical to instant SEQ ID NO:1 as evidenced by Uniprot (see attached handout, protein Accession P80057). Regarding claims 1 and 5, Kumar teaches for use topically in humans (see paragraph 0078, claim 23). Kumar teaches incorporation into a gel, lotion, cosmetic (claim 23) thus meeting the limitations of at least one pharmaceutically or cosmetic acceptable ingredient in instant claim 1. Regarding the limitations of “endopeptidase exhibiting a glutamyl endopeptidase ratio (GR) > 5, where GR is calculated as the enzyme activity exerted by the endopeptidase on substrate Suc-AAPE-pNA divided by the highest of activities exerted by the endopeptidase on substrates Suc- AAPA-pNA, Suc-AAPD-pNA, Suc-AAPF-pNA, Suc-AAPI-pNA, Suc-AAPK-pNA, Suc-AAPL-pNA,Suc-AAPM-pNA, Suc-AAPR-pNA, and Suc-AAPV-pNA”, the peptide of Kumar is identical to instant SEQ ID NO:1 (which is claimed in instant claims 2-3, 19 and 22) and thus, would inherently have the claimed property of a GR>5. This is further evidenced by Applicant’s own specification that shows specific activity for SEQ ID NO:1. Regarding claims 2-3, 19 and 22, Kumar teaches a formulation for use topically (paragraph 0078) comprising at least one proteolytic enzyme, wherein the enzyme is Endo-Glu with a protein accession of P80057 (see paragraph 0089, claim 4) which is identical to instant SEQ ID NO:1 as evidenced by Uniprot (see attached handout, protein Accession P80057). Regarding claim 4, Kumar teaches “Suitable enzyme dosages will usually be in the range of about 0.01-1% (w/w). In various embodiments, the milk and or whey proteins will be present at, for example, about 1-60%, 5- 50%, 20-40%, 10-45%, or about 10-15% milk whey protein content. Thus, enzyme dosage might include amounts such as, e.g., 0.1-1.0%, particularly 0.2% (w/w), corresponding to 2000 IU per 100 g of milk or whey protein. The amount of 0.2% in 100 g would result in 2 mg/g which falls within the range of instant claim 4.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654