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 . 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.
Election/Restrictions
Applicant’s election without traverse of a mix of chemical formulas 3 and 4 at a ratio of 1:9 with phenophoride A, and a second otherwise identical embodiment with GdDOTA in the reply filed on 13 March, 2026 and the phone call with Brandan Chan on 14 April, 2026 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Applicants have elected two formulations, both a mix of formulas 3 and 4, with different agents. A search was conducted for these inventions, and references that rendered them obvious were found. As a result, claims 1-6, 8-16, 19, 20, 24, 25, and 28-30 were examined and claims 7, 17, 18, 20-23, 26, and 27 were withdrawn from consideration. While applicants have stated that they believe their election reads on these claims, claim 7 requires the drug to be attached where the fatty acid is attached in applicant’s elected species, claims 17, 18, and 20 require that both sequences have an oligoarginine sequence (chemical formula 4 does not), claims 21-23 specify formulation parameters that were not elected, and claims 26 and 27 require a hydrophilic and a hydrophobic drug, which was not elected (note that GdDOTA is not a drug, but an imaging agent). Thus, these claims are properly withdrawn.
During examination, a reference was found that anticipated a non-elected species. This reference is discussed below.
Claims Status
Claims 1-30 are pending.
Claims 7, 17, 18, 20-23, 26, and 27 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 13 March, 2026.
Claim Rejections - 35 USC § 112(b)
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.
first rejection
Claim 4 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 4 requires a hydrophobic group attached to α amine of the lysine. The issue is that applicants have not defined hydrophobic, or, more specifically, the cutoff between hydrophobic and not hydrophobic. While the concept of hydrophobicity and hydrophilicity are well understood, there is no art recognized cutoff between hydrophilic and hydrophobic. For example, Zhang et al (US 5,670,483) lists serine, glycine, and threonine as hydrophobic (claim 7), while the University of California Davis online course text (Amino Acids - Biology LibreTexts, downloaded 15 April, 2026) lists all three amino acids as hydrophilic. This means that there is a genus of compounds where it is not clear if the “hydrophobic” limitation is met, rendering the claim indefinite.
second rejection
Claims 8 and 9 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 8 requires a linker selected from a Markush group that includes SEQ IDs 12 and 13. However, the sequence listing is empty at SEQ IDs 12 and 13; there are no sequences there. Claim 9 requires that the hydrophilic peptide have a sequence selected from SEQ IDs 1-7, but SEQ IDs 1, 2, and 6 are also blank.
third rejection
Claims 15 and 16 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 15 requires an average particle diameter, while claim 16 gives an average shell thickness. However, the averaging basis, number weighted, surface weighted, volume weighted, or some other weighting, is not defined, making the claims indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
first rejection
Claims 9, 10, and 19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. All three rejected claims depend from claim 1, which requires that the hydrophilic peptide consist of 2-12 Arg residues. However, these claims allow for the hydrophilic sequence to be RGDRGD, which does not consist of 2-12 Arg residues, making these claims broader in this respect. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
second rejection
Claim 25 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 25 requires that the drug described in claim 24, from which it depends, be hydrophobic, hydrophilic, or a mix. That is every possibility, so this claim does not further limit. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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, 8, 9, 11-13, 15, 16, 24, 25, and 28-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al (KR20180032052A, cited by applicants). Note that Lim et al is in Korean. A machine language translation was used for this rejection; any mention of locations in the reference refer to the machine translation, unless otherwise noted.
Lim et al discuss cyclic peptides that self assemble into nanoparticles (paragraph 3). The cyclic peptide used by the authors is a cyclized version of WWε-KWW-Ebs-TRQARRNRRRRWRR-Ebs (paragraph 32-37, note that the structure is in paragraph 35 of the original document). Note that this compound has an RRRR sequence (SEQ ID 3 of the examined claims) and a Wε-KW sequence, separated by linkers comprising Ebs, anticipating claims 1-3, 8, and 9. The material was assembled into vesicles by various techniques (paragraphs 45-55), anticipating claims 11-13. Note that structures form just from dissolution (paragraph 73). The structures formed by the material were spherical with a diameter of about 40-45 nm, anticipating claim 15. While the thickness of the shell is not described, it is the same compounds as applicants have described, so it will inherently have the same thickness, anticipating claim 16. Assemblies with carboxymethylfluorescien were made (paragraph 63), which were used to deliver the dye to HeLa cells (paragraph 68), anticipating claims 24, 25, 29, and 30. While the pathway by which the material crosses the cell membrane is not described, as these are the same compounds as claimed by applicants, they must use the same mechanism, anticipating claim 28.
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
Claim(s) 1-6, 8, 9, 11-13, 15, 16, 24, 25, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (KR20180032052A, cited by applicants) in view of Kabanov et al (Prot. Eng. (1989) 3(1) p39-42) and Gao et al (Science (Nov. 2021) 24 103220). Note that Lim et al is in Korean. A machine language translation was used for this rejection; any mention of locations in the reference refer to the machine translation, unless otherwise noted.
Lim et al discuss cyclic peptides that self assemble into nanoparticles (paragraph 3), which can be used as a drug delivery mechanism (paragraph 20). The cyclic peptide used by the authors is a cyclized version of WWε-KWW-Ebs-TRQARRNRRRRWRR-Ebs (paragraph 32-37, note that the structure is in paragraph 35 of the original document). Note that this compound has an RRRR sequence (SEQ ID 3 of the examined claims) and a Wε-KW sequence, separated by linkers comprising Ebs. The material was assembled into vesicles by various techniques (paragraphs 45-55). The structures formed by the material were spherical with a diameter of about 40-45 nm. Assemblies with carboxymethylfluorescien were made (paragraph 63), which were used to deliver the dye to HeLa cells (paragraph 68). The Arg residues in the sequence allow the material to penetrate cell membranes, and are responsible for delivery of a cargo into a cell (paragraph 83), but the requirement is for a hydrophilic segment (paragraph 72). As noted above, this reference anticipates claims 1-3, 8, 9, 11-13, 15, 16, 24, 25, and 28-30.
The difference between this reference and the remaining claims is that this reference does not discuss a fatty acid adduct.
Kabanov et al discuss lipid modification of proteins for membrane transport (title). By reacting proteins with stearoyl chloride, they were able to pass through bilayer membranes (p39, 2nd column, 2nd paragraph). This reference discusses using fatty acids to aid in passage through cell membranes.
Gao et al looks at the same method for a different peptide (title). They also showed that the length of the fatty acid affected how efficiently the peptide was transported through the cell membrane, with a maximum uptake in their system with their test sequence being a C14 fatty acid (fig 1e, 3d page, top of page). This reference discusses the effect of changing the length of the fatty acid to optimize uptake.
Therefore, it would be obvious to add the fatty acid of Kabanov et al to the structures of Lim et al, to assist in membrane passage. As this was demonstrated to be effective for different polypeptides and by different groups, an artisan in this field would attempt this modification with a reasonable expectation of success.
Lim et al discusses cyclic peptides that meet the limitations of claim 1, while Kabanov et al renders obvious adding a fatty acid to the sequences. The only obvious location to add it is at the Lys residue in the hydrophobic section, rendering obvious claim 4.
Gao et al renders obvious optimizing the length of the fatty acid. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). Thus, the combination of references renders obvious claims 5 and 6.
second rejection
Claim(s) 1-6, 8-16, 19, 24, 25, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (KR20180032052A, cited by applicants) in view of Kabanov et al (Prot. Eng. (1989) 3(1) p39-42), Gao et al (Science (Nov. 2021) 24 103220), Liu et al (Drug Dev. Res. (2008) 69(6) p329-339), Burgess et al (J. Med. Chem. (1996) 39 p4520-4526) and Sethuraman et al (WO 2019165183). Note that Lim et al is in Korean. A machine language translation was used for this rejection; any mention of locations in the reference refer to the machine translation, unless otherwise noted.
Lim et al discuss cyclic peptides that self assemble into nanoparticles (paragraph 3), which can be used as a drug delivery mechanism (paragraph 20). The cyclic peptide used by the authors is a cyclized version of WWε-KWW-Ebs-TRQARRNRRRRWRR-Ebs (paragraph 32-37, note that the structure is in paragraph 35 of the original document). Note that this compound has an RRRR sequence (SEQ ID 3 of the examined claims) and a Wε-KW sequence, separated by linkers comprising Ebs. The material was assembled into vesicles by various techniques (paragraphs 45-55). The structures formed by the material were spherical with a diameter of about 40-45 nm. Assemblies with carboxymethylfluorescien were made (paragraph 63), which were used to deliver the dye to HeLa cells (paragraph 68). The Arg residues in the sequence allow the material to penetrate cell membranes, and are responsible for delivery of a cargo into a cell (paragraph 83), but the requirement is for a hydrophilic segment (paragraph 72).
Kabanov et al discuss lipid modification of proteins for membrane transport (title). By reacting proteins with stearoyl chloride, they were able to pass through bilayer membranes (p39, 2nd column, 2nd paragraph). This reference discusses using fatty acids to aid in passage through cell membranes.
Gao et al looks at the same method for a different peptide (title). They also showed that the length of the fatty acid affected how efficiently the peptide was transported through the cell membrane, with a maximum uptake in their system with their test sequence being a C14 fatty acid (fig 1e, 3d page, top of page). This reference discusses the effect of changing the length of the fatty acid to optimize uptake.
As noted above, these references render obvious claims 1-6, 8, 9, 11-13, 15, 16, 24, 25, and 28-30.
The difference between these references and the remaining claims is that these references have a different hydrophobic portion of the cyclic peptide.
Liu et al discuss integrin αVβ3 targeted cancer therapy (title). This integrin is expressed in tumor vasculature and some tumors (abstract). This can be used to target anti-cancer agents to the tumor (7th page, 4th paragraph), possibly by RGD containing peptides (4th page, 4th paragraph). This reference discusses targeting integrins to deliver cancer drugs to a tumor.
Burgess et al discuss cyclo RGDRGD, a sequence with selectivity for αVβ3 (title). This showed good binding to the receptor (table 1, p4521, 1st column, top of page), and were active in cells (p4521, 1st column, 3d paragraph). This reference describes a sequence that targets cancer cells.
Sethuraman et al discuss cyclic peptide sequences similar to Lim et al, with an oligoarginine segment, and a stretch of hydrophobic amino acids (paragraph 19). Note that the number of Arg residues can vary, but is at least two, which allow for cell penetrating ability (paragraph 157). This reference discusses oligoarginines in peptides similar to those of Lim et al, to allow cell penetrating ability.
Therefore, it would be obvious to replace the hydrophilic peptide of Lim et al with the sequence of Burgess et al, to target the payload of the constructs of Lim et al to tumor cells, as discussed by Liu et al. As this is a common approach in cancer therapy, an artisan in this field would attempt this modification with a reasonable expectation of success.
Alternatively, it would be obvious to use an oligoarginine, to allow for cell penetrating ability, as mentioned by Sethuraman et al. As Lim et al discusses Arg residues for this purpose (independently suggesting the same modification), an artisan in this field would attempt this modification with a reasonable expectation of success.
Liu et al and Burgess et al render obvious replacing the hydrophilic segment of Lim et al with the sequence RGDRGD. While the resulting sequence (as modified by Kabanov et al and Gao et al) has a WWε-KWW, rather than the Wε-KW sequence of the examined claims, this is not considered a patentable distinction, as the length of a number of repeating units can vary by a small amount and still be considered obvious, absent secondary conditions (MPEP 2144.09). This reconstitutes chemical formula 4, rendering obvious claim 10
Alternatively, Sethuraman et al renders obvious an oligoarginine sequence for the hydrophilic sequence of Lim et al. While it does not specify the 6 Arg residues of applicant’s elected sequence (formula 3), it has an example with 4, and, as noted above, a small difference in the number of repeating units is not considered a patentable distinction, absent secondary considerations (MPEP 2144.09).
The MPEP states that “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. . .the idea of combining them flows logically from their having been individually taught in the prior art" (MPEP 2144.06). Thus, it would be obvious to combine the compound of formula 4 and the compound of formula 3, rendering obvious claim 19.
third rejection
Claim(s) 1-6, 8-16, 19, 24, 25, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (KR20180032052A, cited by applicants) in view of Kabanov et al (Prot. Eng. (1989) 3(1) p39-42), Gao et al (Science (Nov. 2021) 24 103220), Liu et al (Drug Dev. Res. (2008) 69(6) p329-339), Burgess et al (J. Med. Chem. (1996) 39 p4520-4526), Sethuraman et al (WO 2019165183) and Tang et al (Canc. Biol. Ther. (2006) 5-9 p1111-1116). Note that Lim et al is in Korean. A machine language translation was used for this rejection; any mention of locations in the reference refer to the machine translation, unless otherwise noted.
Lim et al discuss cyclic peptides that self assemble into nanoparticles (paragraph 3), which can be used as a drug delivery mechanism (paragraph 20). The cyclic peptide used by the authors is a cyclized version of WWε-KWW-Ebs-TRQARRNRRRRWRR-Ebs (paragraph 32-37, note that the structure is in paragraph 35 of the original document). Note that this compound has an RRRR sequence (SEQ ID 3 of the examined claims) and a Wε-KW sequence, separated by linkers comprising Ebs. The material was assembled into vesicles by various techniques (paragraphs 45-55). The structures formed by the material were spherical with a diameter of about 40-45 nm. Assemblies with carboxymethylfluorescien were made (paragraph 63), which were used to deliver the dye to HeLa cells (paragraph 68). The Arg residues in the sequence allow the material to penetrate cell membranes, and are responsible for delivery of a cargo into a cell (paragraph 83), but the requirement is for a hydrophilic segment (paragraph 72).
Kabanov et al discuss lipid modification of proteins for membrane transport (title). By reacting proteins with stearoyl chloride, they were able to pass through bilayer membranes (p39, 2nd column, 2nd paragraph). This reference discusses using fatty acids to aid in passage through cell membranes.
Gao et al looks at the same method for a different peptide (title). They also showed that the length of the fatty acid affected how efficiently the peptide was transported through the cell membrane, with a maximum uptake in their system with their test sequence being a C14 fatty acid (fig 1e, 3d page, top of page). This reference discusses the effect of changing the length of the fatty acid to optimize uptake.
Liu et al discuss integrin αVβ3 targeted cancer therapy (title). This integrin is expressed in tumor vasculature and some tumors (abstract). This can be used to target anti-cancer agents to the tumor (7th page, 4th paragraph), possibly by RGD containing peptides (4th page, 4th paragraph). This reference discusses targeting integrins to deliver cancer drugs to a tumor.
Burgess et al discuss cyclo RGDRGD, a sequence with selectivity for αVβ3 (title). This showed good binding to the receptor (table 1, p4521, 1st column, top of page), and were active in cells (p4521, 1st column, 3d paragraph). This reference describes a sequence that targets cancer cells.
Sethuraman et al discuss cyclic peptide sequences similar to Lim et al, with an oligoarginine segment, and a stretch of hydrophobic amino acids (paragraph 19). Note that the number of Arg residues can vary, but is at least two, which allow for cell penetrating ability (paragraph 157). This reference discusses oligoarginines in peptides similar to those of Lim et al, to allow cell penetrating ability.
As noted above, these references render obvious claims 1-6, 8-16, 19, 24, 25, and 28-30.
The difference between these references and applicant’s elected species is that these references do not discuss pheophorbide a.
Tang et al discusses pheophorbide a, which is a photodynamic therapy agent that can treat a number of different cancers (abstract). This killed a majority of tumor cells, while sparing normal cells upon irradiation after dosing (p1113, 2nd column, 2nd paragraph). This reference shows that pheophorbide a is an effective therapy for multiple cancers.
Therefore, it would be obvious to add the pheophorbide a to the complex of Lim et al, to provide a therapeutic efficacy to the delivery agent of that reference. As that reference demonstrated delivery of fluorescein to cancer cells, an artisan in this field would attempt this addition with a reasonable expectation of success.
fourth rejection
Claim(s) 1-6, 8-16, 19, 24, 25, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (KR20180032052A, cited by applicants) in view of Kabanov et al (Prot. Eng. (1989) 3(1) p39-42), Gao et al (Science (Nov. 2021) 24 103220), Liu et al (Drug Dev. Res. (2008) 69(6) p329-339), Burgess et al (J. Med. Chem. (1996) 39 p4520-4526), Sethuraman et al (WO 2019165183) and Zhou et al (Biomaterials (2013) 34(31) p7683-7693). Note that Lim et al is in Korean. A machine language translation was used for this rejection; any mention of locations in the reference refer to the machine translation, unless otherwise noted.
Lim et al discuss cyclic peptides that self assemble into nanoparticles (paragraph 3), which can be used as a drug delivery mechanism (paragraph 20). The cyclic peptide used by the authors is a cyclized version of WWε-KWW-Ebs-TRQARRNRRRRWRR-Ebs (paragraph 32-37, note that the structure is in paragraph 35 of the original document). Note that this compound has an RRRR sequence (SEQ ID 3 of the examined claims) and a Wε-KW sequence, separated by linkers comprising Ebs. The material was assembled into vesicles by various techniques (paragraphs 45-55). The structures formed by the material were spherical with a diameter of about 40-45 nm. Assemblies with carboxymethylfluorescien were made (paragraph 63), which were used to deliver the dye to HeLa cells (paragraph 68). The Arg residues in the sequence allow the material to penetrate cell membranes, and are responsible for delivery of a cargo into a cell (paragraph 83), but the requirement is for a hydrophilic segment (paragraph 72).
Kabanov et al discuss lipid modification of proteins for membrane transport (title). By reacting proteins with stearoyl chloride, they were able to pass through bilayer membranes (p39, 2nd column, 2nd paragraph). This reference discusses using fatty acids to aid in passage through cell membranes.
Gao et al looks at the same method for a different peptide (title). They also showed that the length of the fatty acid affected how efficiently the peptide was transported through the cell membrane, with a maximum uptake in their system with their test sequence being a C14 fatty acid (fig 1e, 3d page, top of page). This reference discusses the effect of changing the length of the fatty acid to optimize uptake.
Liu et al discuss integrin αVβ3 targeted cancer therapy (title). This integrin is expressed in tumor vasculature and some tumors (abstract). This can be used to target anti-cancer agents to the tumor (7th page, 4th paragraph), possibly by RGD containing peptides (4th page, 4th paragraph). This reference discusses targeting integrins to deliver cancer drugs to a tumor.
Burgess et al discuss cyclo RGDRGD, a sequence with selectivity for αVβ3 (title). This showed good binding to the receptor (table 1, p4521, 1st column, top of page), and were active in cells (p4521, 1st column, 3d paragraph). This reference describes a sequence that targets cancer cells.
Sethuraman et al discuss cyclic peptide sequences similar to Lim et al, with an oligoarginine segment, and a stretch of hydrophobic amino acids (paragraph 19). Note that the number of Arg residues can vary, but is at least two, which allow for cell penetrating ability (paragraph 157). This reference discusses oligoarginines in peptides similar to those of Lim et al, to allow cell penetrating ability.
As noted above, these references render obvious claims 1-6, 8-16, 19, 24, 25, and 28-30.
The difference between these references and applicant’s elected species is that these references do not discuss Gd-DOTA.
Zhou et al discuss targeting Gd chelates to detect cancer (title). A complex comprising a peptide attached to Gd complexed with DOTA was synthesized (abstract). This showed stronger enhancement of tumors in an animal model than a commercial non-targeted Gd complex or a scrambled targeting complex using T1 weighted MRI imaging (8th page, 1st paragraph). This reference discusses using Gd-DOTA targeted to detect tumors.
Therefore, it would be obvious to add the Gd-DOTA to the formulation rendered obvious by the other references, to provide an ability to detect tumors and tumor vasculature by T1 weighted MRI imaging. As gadolinium is commonly used for similar purposes, and Lim et al shows that their constructs can deliver a cargo to a cancer cell, an artisan in this field would attempt this modification with a reasonable expectation of success.
Conclusion
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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