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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Terminal Disclaimer
The terminal disclaimer filed on 8/13/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US11,712,473 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Response to Arguments
Applicant’s arguments, see Pg 5, filed 2/27/2026, with respect to the claim rejections under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejections have been withdrawn.
Applicant’s arguments, see Pg 7-9, filed 2/27/2026, with respect to the rejection(s) of the claim(s) under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of amendment.
Election/Restrictions
Applicant’s election without traverse of the species formula
-COOCH2CH2CH2CH2CH2CH2CH2CO- as a linker; and a dye as a sensitizer and the species B) skin cancer as a type of cancer to be treated in the reply filed on 1/24/25 is acknowledged.
In the previous Office Action, the elected species was broadened to include SEQ ID NO: 2-4 in addition to the previously elected SEQ ID NO: 6.
In the current Office Action, the elected species is hereby broadened to include the cancer species of breast, pancreatic, head and neck, oesophageal, bladder, and prostate cancer in addition to the elected species of skin cancer.
Claim Status
Claims 1-12 are pending under examination. Claims 1, 2, 3, and 7 are currently amended. Claim 13 is cancelled.
Priority
The instant application is a continuation of the application 16/625,664 (US Patent 11,712,473) filed on 6/25/18, which is the 371 application of the PCT/EP2018/066982, which claims priority to GB1710097.5. The priority date of 6/23/17 based on GB1710097.5 is acknowledged.
New - Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
First rejection – SEQ ID NO: 2
Claims 1, 2, 4, 5, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Tumor-Triggered Drug Release with Tumor-Targeted Accumulation and Elevated Drug Retention To Overcome Multidrug Resistance, Chemistry of Materials, 2016) in view of Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023).
Chen teaches multidrug resistance is one of the main causes of failure in cancer chemotherapy (Abstract). To address this challenge, Chen teaches tumor-triggered nanomedicine comprising a tumor active targeting segment and two programmed therapeutics, one of which is the proapoptotic peptide KLA as shown below:
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, which consists of the instant SEQ ID NO: 2 (Scheme S1 of Ps S2).
Chen further teaches administration of the tumor-triggered nanomedicine compound to mice (subjects) with MCF-7/ADR (breast cancer; Pg 6749-6751, “In vivo anti-MDR evaluation and histological analysis; Figure 8).
Chen does not teach conjugating a sensitizer dye to the conjugate comprising KLA/the instant SEQ ID NO: 2.
Kovar teaches compositions and methods for destroying target cells in a patient using photodynamic therapy. In particular, the invention provides a photosensitizing agent based on a small molecular weight protein or peptide or a small molecule that is conjugated to a phthalocyanine dye (Abstract).
Kovar teaches that photodynamic therapy is a treatment method that uses a photosensitizing agent and irradiating light to destroy cells of interest in the body. When the photosensitizer is exposed to a specific wavelength of light, it produces a cytotoxic reactive oxygen species that can induce apoptosis, necrosis and/or autophagy of nearby cells (Col. 1, lines 25-30).
Kovar teaches treating various species of cancer with the peptide-dye conjugates, including breast, pancreatic, skin, head and neck, oesophageal, bladder, and prostate cancer (Col. 1, lines 56-64).
In summary, Chen teaches a method of treating breast cancer in a subject in need thereof comprising administering a peptide conjugate comprising a peptide consisting of SEQ ID NO: 2. Kovar teaches a method of treating breast and other cancers in a subject in need thereof through administration of a peptide-dye conjugate that can be used in photodynamic therapy.
Therefore, regarding claims 1 and 2, it would be prima facie obvious to combine the peptide conjugates into one conjugate comprising the peptide consisting of the instant SEQ ID NO: 2 and the photodynamic therapy dye. One skilled in the art would be motivated to do so in order to more effectively treat breast cancer. One would have a reasonable expectation of success as Chen and Kovar both teach peptide conjugates for the treatment of breast cancer.
Additionally, per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "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). By extension of this logic, it would be obvious to combine peptide conjugate of Chen with the peptide conjugate of Kovar into one because both are designed to effectively treat breast cancer.
Regarding claim 4, Kovar teaches a linker between the sensitizer dye and the peptide (Col. 9, lines 27-45; Col. 16, lines 41-67; also see, for example, segment “L” of the compound shown on Col. 17-18).
Regarding claim 5, Kovar teaches the linker may be a polymer with a repeating -(CH2)n- group (Col. 16, lines 59-64).
Regarding claim 8, Kovar teaches the conjugates of the invention can be activated by a trigger (Col. 1, lines 25-30; Col. 22, lines 22-27).
Regarding claims 9 and 10, as stated above, Kovar teaches that photodynamic therapy is a treatment method that uses a photosensitizing agent and irradiating light to destroy cells of interest in the body. When the photosensitizer is exposed to a specific wavelength of light, it produces a cytotoxic reactive oxygen species that can induce apoptosis, necrosis and/or autophagy of nearby cells (Col. 1, lines 25-30). The forms of energy used for administering photodynamic therapy (trigger) include, but are not limited to, light, thermal, sonic, ultrasonic, chemical, microwave, ionizing (such as x-ray and gamma ray), mechanical, and electrical. The term “radiation” includes all wavelengths and all wavebands (Col. 22, lines 22-27). Per the instant specification, photodynamic therapy uses light (electromagnetic radiation; [0006]).
Regarding claims 11 and 12, as stated above, Kovar teaches sound as a trigger. Per the instant specification, sonodynamic therapy uses sound ([0007]). Thus, Kovar teaches sonodynamic therapy as triggered by sound.
Claims 1, 2, 4-6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Tumor-Triggered Drug Release with Tumor-Targeted Accumulation and Elevated Drug Retention To Overcome Multidrug Resistance, Chemistry of Materials, 2016) and Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023), as applied to claims 1, 2, 4, 5, and 8-12 above, and further in view of Costley et al. (Costley D, Nesbitt H, Ternan N, Dooley J, Huang YY, Hamblin MR, McHale AP, Callan JF. Sonodynamic inactivation of Gram-positive and Gram-negative bacteria using a Rose Bengal-antimicrobial peptide conjugate. Int J Antimicrob Agents. 2017 Jan;49(1):31-36., cited on IDS filed 12/5/2023).
The teachings of Chen and Kovar have been set forth above. Chen and Kovar do not teach a linker of the general formula -COOCH2CH2CH2CH2CH2CH2CH2CO-.
Costley teaches conducting sonodynamic therapy to treat Gram-negative and Gram-positive bacterial infections using a Rose Bengal (dye)-antimicrobial peptide conjugate (Title, Abstract). Costley teaches the following compound consisting of Rose Bengal conjugated to SEQ ID NO: 2 by a -COOCH2CH2CH2CH2CH2CH2CH2CO- linker (Figure 1; Pg 32, “2. Materials and methods”).
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The Rose Bengal-SEQ ID NO: 2 conjugate can generate reactive oxygen species (ROS) upon exposure to low-intensity ultrasound (Pg 32, “3. Results and discussion,” first paragraph and Figure 2).
In summary, Chen and Kovar teach a method of treating breast cancer in a subject in need thereof comprising administering a peptide conjugate comprising a peptide consisting of the instant SEQ ID NO: 2 and a sensitizer dye. Costley teaches a peptide conjugate comprising a peptide consisting of the instant SEQ ID NO: 2 and a sensitizer dye connected via the linker -COOCH2CH2CH2CH2CH2CH2CH2CO-.
Therefore, regarding claim 6, it would be prima facie obvious to incorporate the linker into the peptide conjugate used in the method of treating breast cancer taught by Chen and Kovar. One skilled in the art would be motivated to do so as Costley teaches similar peptide conjugates comprising linkers attaching a peptide moiety to a sensitizer dye. One would have a reasonable expectation of success as Costley established that the peptide conjugate containing the linker could produce ROS as a part of sonodynamic therapy.
Claims 1, 2, 4, 5, and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Tumor-Triggered Drug Release with Tumor-Targeted Accumulation and Elevated Drug Retention To Overcome Multidrug Resistance, Chemistry of Materials, 2016) and Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023), as applied to claims 1, 2, 4, 5, and 8-12 above, and further in view of Stereochemistry of the Amino Acids (“Stereochemistry,” 2007, accessed from https://webhost.bridgew.edu/fgorga/proteins/stereochem.htm on 5/6/2026).
The teachings of Chen and Kovar have been set forth above. Chen and Kovar do not expressly teach the peptide of the conjugate has at least one L enantiomer amino acid.
Stereochemistry teaches the L-forms of amino acids are the most common (line 2).
Therefore, regarding claim 7, it would be prima facie obvious to at have at least one amino acid in the peptide conjugate taught by Chen and Kovar be an L enantiomer amino acid. One skilled in the art would be motivated to do so and have a reasonable expectation of success because most peptides are made of L form amino acids.
Second rejection – SEQ ID NO: 3 and 6
Claims 1, 2, 4, 5, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Burns et al. (pH-Selective Cytotoxicity of pHLIP-Antimicrobial Peptide Conjugates. Sci Rep 6, 28465 (2016).) in view of Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023).
Burns teaches positively charged antimicrobial peptides have become promising agents for the treatment of cancer by inducing apoptosis through their preferential binding and disruption of negatively charged membranes. (KLAKLAK)2 is such a peptide but due to its polarity it cannot cross the cellular membrane and therefore relies on the use of a delivery agent (Abstract). Burns set out to investigate if pH(Low) insertion peptide (pHLIP) could target (KLAKLAK)2 and fragments thereof to cancer cells (Abstract; Pg 1, second paragraph). Burns investigated multiple peptide fragments including KLAK (equivalent to the instant SEQ ID NO: 3) and KLAKLAK (Pg 3, Table 1). These fragments were then coupled to the Cys residue of pHLIP, as shown in Figure 1. The coupling of pHLIP to KLAKLAK reads on the instant SEQ ID NO: 6. The pHLIP-KLAK fragment peptides were then used to treat MDA-MB-231 breast cancer cells in vitro (Pg 3, 4th and 5th paragraphs; Figure 2 and 3).
Burns does not teach administering the above peptide conjugates to a subject in need thereof nor a peptide conjugate comprising a sensitizer dye.
Kovar teaches compositions and methods for destroying target cells in a patient using photodynamic therapy. In particular, the invention provides a photosensitizing agent based on a small molecular weight protein or peptide or a small molecule that is conjugated to a phthalocyanine dye (Abstract).
Kovar teaches that photodynamic therapy is a treatment method that uses a photosensitizing agent and irradiating light to destroy cells of interest in the body. When the photosensitizer is exposed to a specific wavelength of light, it produces a cytotoxic reactive oxygen species that can induce apoptosis, necrosis and/or autophagy of nearby cells (Col. 1, lines 25-30).
Kovar teaches treating various species of cancer with the peptide-dye conjugates, including breast, pancreatic, skin, head and neck, oesophageal, bladder, and prostate cancer (Col. 1, lines 56-64).
In summary, Burns teaches treating breast cancer cells with a peptide conjugate comprising a peptide consisting of SEQ ID NO: 3 or SEQ ID NO: 6. Kovar teaches a method of treating breast and other cancers in a subject in need thereof through administration of a peptide-dye conjugate that can be used in photodynamic therapy.
Therefore, regarding claims 1 and 2, it would be prima facie obvious to combine the peptide conjugates into one conjugate comprising a peptide consisting of either the instant SEQ ID NO: 3 or 6 and the photodynamic therapy dye. One skilled in the art would be motivated to do so in order to more effectively treat breast cancer. One would have a reasonable expectation of success as Burns and Kovar both teach peptide conjugates for the treatment of breast cancer.
Additionally, per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "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). By extension of this logic, it would be obvious to combine peptide conjugate of Burns with the peptide conjugate of Kovar into one because both are designed to effectively treat breast cancer.
Regarding claim 4, Kovar teaches a linker between the sensitizer dye and the peptide (Col. 9, lines 27-45; Col. 16, lines 41-67; also see, for example, segment “L” of the compound shown on Col. 17-18).
Regarding claim 5, Kovar teaches the linker may be a polymer with a repeating -(CH2)n- group (Col. 16, lines 59-64).
Regarding claim 8, Kovar teaches the conjugates of the invention can be activated by a trigger (Col. 1, lines 25-30; Col. 22, lines 22-27).
Regarding claims 9 and 10, as stated above, Kovar teaches that photodynamic therapy is a treatment method that uses a photosensitizing agent and irradiating light to destroy cells of interest in the body. When the photosensitizer is exposed to a specific wavelength of light, it produces a cytotoxic reactive oxygen species that can induce apoptosis, necrosis and/or autophagy of nearby cells (Col. 1, lines 25-30). The forms of energy used for administering photodynamic therapy (trigger) include, but are not limited to, light, thermal, sonic, ultrasonic, chemical, microwave, ionizing (such as x-ray and gamma ray), mechanical, and electrical. The term “radiation” includes all wavelengths and all wavebands (Col. 22, lines 22-27). Per the instant specification, photodynamic therapy uses light (electromagnetic radiation; [0006]).
Regarding claims 11 and 12, as stated above, Kovar teaches sound as a trigger. Per the instant specification, sonodynamic therapy uses sound ([0007]). Thus, Kovar teaches sonodynamic therapy as triggered by sound.
Claims 1, 2, 4-6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Burns et al. (pH-Selective Cytotoxicity of pHLIP-Antimicrobial Peptide Conjugates. Sci Rep 6, 28465 (2016).) and Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023), as applied to claims 1, 2, 4, 5, and 8-12 above, and further in view of Costley et al. (Costley D, Nesbitt H, Ternan N, Dooley J, Huang YY, Hamblin MR, McHale AP, Callan JF. Sonodynamic inactivation of Gram-positive and Gram-negative bacteria using a Rose Bengal-antimicrobial peptide conjugate. Int J Antimicrob Agents. 2017 Jan;49(1):31-36., cited on IDS filed 12/5/2023).
The teachings of Burns and Kovar have been set forth above. Burns and Kovar do not teach a linker of the general formula -COOCH2CH2CH2CH2CH2CH2CH2CO-.
Costley teaches conducting sonodynamic therapy to treat Gram-negative and Gram-positive bacterial infections using a Rose Bengal (dye)-antimicrobial peptide conjugate (Title, Abstract). Costley teaches the following compound consisting of Rose Bengal conjugated by a -COOCH2CH2CH2CH2CH2CH2CH2CO- linker to a peptide moiety (Figure 1; Pg 32, “2. Materials and methods”).
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The conjugate can generate reactive oxygen species (ROS) upon exposure to low-intensity ultrasound (Pg 32, “3. Results and discussion,” first paragraph and Figure 2).
In summary, Burns and Kovar teach a method of treating breast cancer in a subject in need thereof comprising administering a peptide conjugate comprising a peptide consisting of either the instant SEQ ID NO: 3 or 6 and a sensitizer dye. Costley teaches a peptide conjugate comprising a sensitizer dye connected to a peptide moiety via the linker -COOCH2CH2CH2CH2CH2CH2CH2CO-.
Therefore, regarding claim 6, it would be prima facie obvious to incorporate the linker into the peptide conjugate used in the method of treating breast cancer taught by Burns and Kovar. One skilled in the art would be motivated to do so as Costley teaches similar peptide conjugates comprising linkers attaching a peptide moiety to a sensitizer dye. One would have a reasonable expectation of success as Costley established that the peptide conjugate containing the linker could produce ROS as a part of sonodynamic therapy.
Claims 1, 2, 4, 5, and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Burns et al. (pH-Selective Cytotoxicity of pHLIP-Antimicrobial Peptide Conjugates. Sci Rep 6, 28465 (2016).) and Kovar et al. (US10588972 B2, filed 6/2/2015, cited on IDS filed 12/5/2023), as applied to claims 1, 2, 4, 5, and 8-12 above, and further in view of Stereochemistry of the Amino Acids (“Stereochemistry,” 2007, accessed from https://webhost.bridgew.edu/fgorga/proteins/stereochem.htm on 5/6/2026).
The teachings of Burns and Kovar have been set forth above. Burns and Kovar do not expressly teach the peptide of the conjugate has at least one L enantiomer amino acid.
Stereochemistry teaches the L-forms of amino acids are the most common (line 2).
Therefore, regarding claim 7, it would be prima facie obvious to have at least one amino acid in the peptide conjugate taught by Burns and Kovar be an L enantiomer amino acid. One skilled in the art would be motivated to do so and have a reasonable expectation of success because most peptides are made of L form amino acids.
Allowable Subject Matter
As stated in the prior Office Action, a method of treating cancer in a subject in need thereof comprising administering a sensitizer-peptide conjugate comprising at least one sensitizer and at least one peptide to the subject, wherein the at least one sensitizer is a dye; and wherein the at least one peptide comprises a sequence SEQ ID NO: 4; and wherein the cancer is selected from the group consisting of breast, pancreatic, skin, head and neck, oesophageal, bladder, and prostate cancer, is allowable (emphasis added). The closest prior art is US20050277589A1 (published 12/15/2005), which teaches treating infections caused by pathogenic agents such as bacteria and fungi with SEQ ID NO: 12. The difference between SEQ ID NO: 12 and the instant SEQ ID NO: 4 is that the N-terminal Cys residue is not present in SEQ ID NO: 12. US20050277589A1 also does not provide any teachings, suggestions, or motivations as to why one skilled in the art would seek to create a peptide conjugate comprising SEQ ID NO: 12 and a sensitizer dye nor why one would motivated to use such a peptide conjugate to treat any of the cancer species listed in claim 1.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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