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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15, as well as the following species
First amphiphilic dendron coil: hydrophobic core-forming component (poly(ɛ-caprolactone)) covalently linked to a first polyester dendron (a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron) which is covalently linked to a first a methoxy poly(ethylene glycol) (mPEG) moiety, wherein the first mPEG moiety comprises a first conjugated immunotherapeutic peptide which binds the PD-L1 receptor, specifically HVVWHRESPSGQTDTLAA SEQ ID NO:5;
Second amphiphilic dendron coil: hydrophobic core-forming component (poly(ɛ-caprolactone)) covalently linked to a first polyester dendron (a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron) which is covalently linked to a first a methoxy poly(ethylene glycol) (mPEG) moiety, wherein the first mPEG moiety comprises a first conjugated immunotherapeutic peptide which binds the PD-L1 receptor, specifically HVVWHRESPSGQTDTLAA SEQ ID NO:5;
Third amphiphilic dendron coil: hydrophobic core-forming component (poly(ɛ-caprolactone)) covalently linked to a first polyester dendron (a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron) which is covalently linked to a first a methoxy poly(ethylene glycol) (mPEG) moiety, wherein the first mPEG moiety;
Ligand: an imaging agent;
Condition: TNBC
On complete search, the examiner concluded that the election of species requirement for the first, second, and third amphiphilic dendron-coils and the ligand of claim 14 were not necessary for examination and therefore the requirement for election of these four species only is hereby withdrawn. The species election for condition remain in effect.
Claims 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/30/2025.
Claims 1-15 are under current examination.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that page 20 recites a mouse sequence, SEQ ID 8; however only SEQ ID 1-7 are present in the application currently. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 recites “any of claim 1” in line 2. This appears to be a typographical error. Appropriate correction is required.
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.
Claims 7-11 and 14 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 7 recites the limitation "the immune checkpoint receptor" in line 2. There is insufficient antecedent basis for this limitation in the claim. Did Applicant intend for claim 7 to depend from claim 6?
Claim 8 recites the limitation "the growth factor receptor" in line 2. There is insufficient antecedent basis for this limitation in the claim. Did Applicant intend for claim 8 to depend from claim 6?
Regarding claim 9, the phrase "specifically" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 10, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11, the phrase "specifically" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17840964 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims.
Inter alia, the claims of the ‘964 application embrace a self-assembled therapeutic dendron-micelle, comprising a first amphiphilic dendron-coil, a second amphiphilic dendron-coil, and optionally a third amphiphilic dendron-coil; and an encapsulatedBRD4 ligand, or salt thereof, or a BRD4 ligand linker-ubiquitin ligase cereblon ligand or salt thereof (i.e. a chemotherapy agent); wherein the first amphiphilic dendron-coil comprises a first non-peptidyl, hydrophobic core-forming component covalently linked to a first polyester dendron which is covalently linked to first a poly(ethylene glycol) (PEG) moiety, wherein the first PEG moiety comprises a first conjugated therapeutic peptide; wherein the second amphiphilic dendron-coil comprises a second non-peptidyl, hydrophobic core-forming component covalently linked to a second polyester dendron which is covalently linked to a second poly(ethylene glycol) (PEG) moiety, wherein the second PEG moiety does not comprise a conjugated peptide, and optionally a third amphiphilic dendron-coil, wherein the third amphiphilic dendron- coil comprises a third non-peptidyl, hydrophobic core-forming component covalently linked to a third polyester dendron which is covalently linked to a third poly(ethylene glycol) (PEG) moiety, wherein the third PEG moiety comprises a second therapeutic binding peptide (i.e. three amphiphilic dendron-coils, two of which are conjugated to a peptide at the PEG moiety, and one of which that is not conjugated to a peptide at the PEG moiety). More specifically, the non-peptidyl hydrophobic core may be polycaprolactone (PCL), the polyester dendron may be a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron, and the PEG may be mPEG (limitations of instant claims 1, 3, 9, 11, and 12). The linear hydrophobic polymer (e.g. the PCL segment) has a molecular weight ranging from 0.5 to 20 kDa and the PEG moiety has a molecular weight ranging from about 0.2 to 5 kDa (limitations of instant claims 10 and 13). The peptides may bind PD-L1, PD-1, or PDGFR, among others, and any combination of therapeutic peptides is considered within the scope of the ‘964 application. The PEG moiety may be linked to an image contrast agent. The claims of the ’964 application embrace a pharmaceutical composition formed from the claimed micelles.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 9212258 (cited in the IDS filed 04/21/2023); and
claims 1-35 of U.S. Patent No. 10543171
in view of Li et al (Cancer Letters 418, pages 1-9; publication year: 2018) and Boohaker et al. (Cancer Letters 434, page 11-21; publication year: 2018), as evidenced by Cutler et al. (US 20030185831; publication date: 10/02/2003).
Inter alia, the claims of the patents embrace a micelle (‘258 patent) or a method of using a micelle (‘317 patent) comprising multiple amphiphilic dendron coils, each formed from covalently linked non-peptidyl hydrophobic core, polyester dendron, and PEG. More specifically, the non-peptidyl hydrophobic core may be polycaprolactone (PCL), the polyester dendron may be a generation 3 polyester-8-hydroxyl-1-acetylene bis-MPA dendron, and the PEG may be mPEG (limitations of instant claims 1, 3, 9, 11, and 12). The linear hydrophobic polymer (e.g. the PCL segment) has a molecular weight ranging from 0.5 to 20 kDa and the PEG moiety has a molecular weight ranging from about 0.2 to 5 kDa (limitations of instant claims 10 and 13). The micelle encapsulates a cancer drug (i.e. a chemotherapy drug; limitation of instant claim 2), and the PEG moiety can be conjugated to a ligand. Turning to the specification, the term “ligand” embraces “Interferon (IFN)-alpha, IFN-beta, IFN-gamma, CXCL10, Interleukin (IL)-4, IL-12, Transforming Growth Factor Beta inhibitor, a gamma-type Peroxisome Proliferator-Activated Receptor (PPARy) ligand, an angiotensin activity inhibitor, a Platelet-Derived Growth Factor (PDGF) inhibitor” (col 7-8 of the ‘258 patent; col 10 of the ‘171 patent) as well as Herceptin (i.e. an inhibitor of EGFR; see Cutler’s claim 15: EGF inhibitor is Herceptin; col 8 of the ‘258 patent, col 11 of the ‘171 patent). The aforementioned peptides affect the immune system and are therefore considered “immunotherapeutic” (limitation of instant claim 1).
With regard to the requirement that the micelle comprise a first through third (instant claim 1), or fourth (instant claim 3) amphiphilic dendron-coil, the patents embrace micelles formed from greater than one amphiphilic dendron-coil. With regard to the recitation in instant claim 1 requiring that one of the third amphiphilic dendron coils lack a conjugated ligand, noting that instant claim language describing the first – third amphiphilic dendron coils embraces micelles in which all three amphiphiles are identical except that two must have a ligand conjugated to the PEG moiety, and one must not have a ligand conjugated to the PEG moiety, it would have been obvious to one of ordinary skill that the micelle must contain a sufficient number of amphiphilic molecules to stably maintain the micelle structure (e.g. a vesicle formed from the thermodynamic stability achieved when hydrophobic moieties interact with each other, and hydrophilic moieties interact with each other and the surrounding solvent). The examiner considers any arrangement of ligand-containing vs. ligand-lacking amphiphiles to have been prima facie obvious so long as the micelle remains functional, i.e. a thermodynamically stable micelle structure that is also capable of achieving the object intended in linking the PEG moiety to a ligand.
With regard to claims 4-8, Although the claims of the cited patents embrace multiple different peptide ligands that modulate the immune system, as noted above, there is not a particular reason set forth in the cited patent claims to select a first and a second immunotherapeutic peptide to conjugate to the amphiphilic dendron-coil.
Li discloses that co-treatment with EGFR inhibitors and PD-1/PD-L1 immune checkpoint inhibitors may improve outcome in cancer (NSCLC) by targeting signaling in patients with EGFR activating mutations and immune suppression in the environment of the tumor (title, abstract).
Boohaker discloses a peptide inhibitor for the PD-1/PD-L1 interaction that allows for CTL (cytotoxic T-lymphocyte) anti-tumor activity (abstract, title).
It would have been prima facie obvious to select an EGF ligand such as Herceptin from the ligands embraced by the cited patents for conjugation with the amphiphilic dendron-coils and combine it for co-delivery with a PD-1/PD-L1 inhibitory peptide disclosed by Boohaker to arrive at a micelle comprised of amphiphilic dendron-coils conjugated to both of these immunotherapeutic peptides, either together or separately, along with sufficient unconjugated amphiphilic dendron-coils to form a stable micelle from the amphiphiles bearing the therapeutic peptides. The skilled artisan would have been motivated to combine e.g. Herceptin with a PD-1/PD-L1 inhibitory peptide in order to both interrupt pro-tumorigenic EGFR signaling and attenuate immunosuppression in the vicinity of the tumor. The artisan of ordinary skill would have had reasonable expectation of success because the patents embrace dendron-coils conjugated to any ligand, the amphiphilic dendron coils had been established to form micelles, and because this particular combination of ligands was known to show benefit in anti-cancer therapy.
With regard to instant claims 3 and 14, the claim as it is currently worded only requires a ligand to be present anywhere within the micelle. This reads on combinations of any of the above ligands embraced by the cited patents.
With regard to claim 15, as the inventions of the cited patents embrace compositions intended for pharmaceutical use, they are considered to be pharmaceutical compositions.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (US9212258; issue date: 12/15/2015; cited in the IDS filed 04/21/2023) in view of Li et al (Cancer Letters 418, pages 1-9; publication year: 2018) and Boohaker et al. (Cancer Letters 434, page 11-21; publication year: 2018), as evidenced by Cutler et al. (US 20030185831; publication date: 10/02/2003).
The claims are rejected as obvious under 35 USC 103 exactly as set forth in the double patenting rejection above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617