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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE on 7/28/26 and the amendment of claims has been entered.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 11/3/25 was previously acknowledged.
The requirement was deemed proper and made FINAL.
In the reply filed 4/8/26, Applicants amended claims 1-3.
In the RCE filed 7/28/26, Applicants amended claim 1.
Claim 1-6 are pending.
Claims 4-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claim 1-3 are under examination.
Claim Objections-Withdrawn
The objection to claim 1 is withdrawn.
.
Nucleotide and/or Amino Acid Sequence Disclosures-Maintained
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825. This application contains a “Sequence Listing” as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)). A copy of the "Sequence Listing" in computer readable form (CRF) has been submitted; however, the content of the CRF does not comply with one or more of the requirements of 37 CFR 1.822 through 1.824, as indicated in the "Error Report" that indicates the "Sequence Listing" could not be accepted. Refer to document "Sequence listing in computer readable format is defective" dated 7/28/26.
Required response – Applicant must provide:
A replacement "Sequence Listing" part of the disclosure, as described above in item 1); together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter and
An amendment to the specification to remove the “Sequence Listing previously submitted as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3))
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, Applicant must also provide:
A CRF in accordance with 1.821(e)(1) or 1.821(e)(2) as required by 37 CFR 1.825(b)(6)(ii); and
Statement according to item 2) a) or b) above.
Response to Arguments
Applicant's arguments filed 7/28/26 have been fully considered but they are not persuasive. Applicants state that a corrected sequence listing in ST.25 format with statements required under 37 CFR 1.825(b)(4)-(5) were submitted.
This argument is not persuasive as the sequence listing filed 7/28/26 is defective. Applicants are encouraged to contact the USPTO sequence help desk at 571-272-2510 or email SequenceHelpDesk@USPTO.GOV to correct the issue.
Claim Rejections - Withdrawn
The rejection of claims 1-3 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 is withdrawn due to amendment of claim 1.
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 1-3 under 35 U.S.C. 103 as being unpatentable over Hantash (WO2009003037, cited on IDS and provided by Applicants) in view of Hantash et al. (WO2012/154959, referred to as Hantash 2) is maintained.
Hantash teaches peptides which inhibit the enzymatic activity of tyrosinase as well as formulations and methods for their use in the reduction of skin pigmentation (Abstract). Hantash teaches the peptide PLG-OH, which is identical to instantly claimed SEQ ID NO: 2 (Abstract, claim 1). Hantash teaches treatment involving lightening of the skin and other conditions including melanoma (p. 28, lines 21-29). Hantash teaches tyrosinase is an attractive target for melanoma treatment (p. 28, lines 21-29). Hantash teaches that PLG was cytotoxic to melanocytes (Table on top of p. 35). Hantash teaches an example of PLG-OH administered in the B16 pigmentation assay. B16 cells is mouse melanoma cell line. PLG-OH was found to be cytotoxic to the mouse melanoma cells (B16 cells) (page 35, table).
Hantash does not teach PLG-OH in combination with RRFVLL (SEQ ID NO: 1) or an example of administration of the peptides to a subject in need of treatment, such as a subject with melanoma. However, the teachings of Hantash and Hantash 2 are suggestive of the limitations.
Hantash 2 teaches the peptide RRFVLL which is identical to instantly claimed SEQ ID NO: 1 (p. 13, “P14 peptide” SEQ ID NO: 5). Hantash 2 teaches the peptides may be used for other treatments such melanoma (top of p. 33). Hantash 2 teaches that the peptides do not cause cancer and are not toxic to skin cells as does hydroquinone (top of p. 13). Hantash 2 defines “non-toxic” as not toxic to human melanocytes (p. 18, lines 20-22). Hantash 2 teaches that the peptides may be used in combination with other compounds (bottom of p. 27). Hantash 2 teaches that tyrosinase is an excellent target for essentially all patients with melanoma (first para. of p. 33).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to administer the peptide PLG-OH (instantly claimed SEQ ID NO: 2) and RRFVLL (instantly claimed SEQ ID NO: 1) to a subject with melanoma because Hantash teaches the peptide was cytotoxic to melanoma cells. A person of ordinary skill in the art would look to the teachings of Hantash and Hantash 2 and have a motivation to administer PLG-OH and RRFVLL because they are tyrosinase inhibitors and tyrosinase inhibitors are attractive targets for melanoma treatment according to Hantash and Hantash 2. There is a reasonable expectation of success given that the PLG-OH was effective in melanoma cells. 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 the instant case, Hantash teaches SEQ ID NO: 2 for melanoma and Hantash 2 teaches SEQ ID NO: 1 for treatment of melanoma. Therefore the prior art teaches the compositions useful for the same purpose. A reasonable expectation of success is expected given that each components are potential treatments for melanoma.
With respect to the limitation “inducing selective cytotoxicity”, “wherein the oligopeptide inhibits MAPK signaling, thereby inducing apoptosis of the melanoma cells”, the oligopeptides from Hantash and Hantash 2 would inherently have all of the activities and properties of the claim 1. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Hantash and Hantash 2 makes obvious administering the same peptides to the same patient population (subject with melanoma), therefore the composition would necessarily have the same properties. Importantly, Hantash 2 teaches that the peptides do not cause cancer and are not toxic to skin cells as does hydroquinone (top of p. 13). Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Importantly, MPEP 2112 states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer” and “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.”
With respect to claims 2 and 3, Hantash teaches administration of the peptide to mouse melanoma cells (p. 34, lines 16-17 and Table on p. 35). Hantash also teaches the formulation for administration to humans (p. 14, lines 12-13).
Response to Arguments
Applicant's arguments filed 7/28/26 have been fully considered but they are not persuasive. Applicants argue that Hantash cytotoxicity data for PLG-OH is derived from the B16 assay in which the measured endpoint is melanin/pigment production rather than cell viability, apoptosis or comparative selectivity across cell types. Applicants argue that Hantash’s disclosed utility for PLG-OH is inhibition of tyrosinase to reduce melanin synthesis for cosmetic purposes. Applicants argue the property recited in claim 1 is a comparative cell viability outcome measure directly in the specification using MTT and trypan blue exclusion assays (Table !A-3F, Fig. 4-14). This data shows that the identical chemical species produces only minimal cytotoxicity toward normal human melanocytes and fibroblasts, while remaining toxic to melanoma cells in contrast to hydroquinone. Applicants argue that because Hantash’s own data addresses a different assay endpoint directed to a different purpose, the record does not establish that the claimed comparative viability bases selectivity is the natural and unavoidable result of the shared structure. Applicants argue that it establishes only that the same molecule was tested for a different purpose and produced a different category of data. Applicants argue that the burden of inherency was not met. Applicants argue that Hantash 2 disclose purpose was directed to identifying tyrosinase inhibiting skin lightening peptides. Applicants argue that neither reference is shown to measure, target or discuss MAPK, BRAF or CRAF pathway mediated apoptosis nor any comparative studies for cytotoxicity across multiple normal skin cell types. Applicants argue that the only common thread between the two references is that both references were screened for tyrosinase related activity and neither reference measures or predicts the specific comparative cytotoxicity profile now claimed. Applicants argue that even if PHOSITA was motivated to combine the peptides for tyrosinase related purposes, neither Hantash 1 or 2 provide a basis to expect that the combination would produce the specific comparative data now claimed (i.e. reduced cytotoxicity toward normal human melanocytes, keratinocytes and fibroblasts relative to hydroquinone). Applicants argue that a reasonable expectation of success requires an expectation of the specific claimed result not merely an expectation that each component would retain its previously known tyrosinase activity.
These arguments were considered but are not persuasive. As indicated above, it would have been obvious to combine both peptides because the art teaches them for the same purpose (see MPEP 2144.06). The argument that the instant peptides induce cytotoxicity in melanoma cells while sparing healthy cells and that the peptides of the prior art are tyrosinase inhibitors essential for melanin synthesis, is not persuasive because the peptides are the same. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Importantly, MPEP 2112 states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer” and “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.” In the instant case, the claimed selective cytotoxicity is an inherent property of the claimed peptides themselves. The prior art does not have to recognize or expressly test that property for it to be inherently present when the peptides are administered under the claimed conditions. In other words, if the peptides are selectively cytotoxic to certain cells while exhibiting no toxicity to others, that property necessarily accompanies the use of the peptides. Importantly, Hantash 2 teaches that the peptides do not cause cancer and are not toxic to skin cells as does hydroquinone (top of p. 13). Hantash 2 defines “non-toxic” as not toxic to human melanocytes (p. 18, lines 20-22). Therefore, Hantash 2 clearly teaches that the P14 is not toxic to skin cells. For the reasons presented in the rejection above, the burden of inherency was met.
For the reasons presented above, the rejection is maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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