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 .
Status of Claims
Claims 1-24 are pending. Claims 19-24 are withdrawn. Claims 1-18 are under examination.
Priority
This application claims priority to US provisional application 63/321,125 filed on 3/18/2022.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/28/2023 has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-18) and species a) GRGDS and b) DBCO-PEG-b-PLGA in the reply filed on 1/6/2026 is acknowledged.
Claims 19-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1/6/2026.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7, 11, 15, 17 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a composition of natural products without significantly more. The claim(s) recite(s) a targeting component, a crosslinking component, polypeptide sequences that bind to a receptor on an activated platelet or von Willebrand factor, a polypeptide sequence that comprises the sequence GRGDS, hydrophilic and hydrophobic components and nanoparticles. This judicial exception is not integrated into a practical application because each of the components and sequences encompasses natural proteins where some natural proteins are configured to bind other proteins such as extracellular proteins, growth factors, receptors and antibodies or intracellular proteins such as signaling proteins. Proteins are able to crosslink via disulfide bonds between cysteines or by interactions with post-translationally modified groups. There are natural factors and proteins that bind to receptors on activated platelets or to von Willebrand factor. There are natural proteins that contain at least one sequence group that is GRGDS. These are proteins that adhere to cells such as collagen, fibronectin and tenascin C which have the GRGDSP sequence (one of the RGD peptide sequences that is sometimes used to attach to biomaterials) (Hwang et al (Biomaterials, 2007,volume 28, pages 4039-4046; see Hwang introduction). Hwang indicates that “The RGD sequence is the ligand for integrin-mediated cell adhesion, which involves a cascade of four overlapped reactions—cell attachment, cell spreading, actin-skeleton formation, and focal-adhesion formation—and which is important for transmitting signals related to cell behavior and the cell cycle” (Hwang Introduction). Many proteins exist that have natural hydrophobic and hydrophilic domains to control their interactions with the cell and other proteins/molecules. For example, a transmembrane receptor has hydrophilic portions that extend extracellularly or into the cytoplasm while having hydrophobic transmembrane domains. Nanoparticles may include natural components of cells such as nanovesicles that carry natural items. Packaging with separating the natural products does not alter the natural products themselves as they can still exist as natural molecules. It is routine and conventional to package items for storage in the art. Merely isolating a natural compound does not necessarily make that natural compound patent eligible. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims that have broad recitations that provides for naturally occurring items that function as they would naturally based on naturally occurring structures and abilities to naturally cross-link.
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.
Claims 1-18 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 1 is indefinite for utilizing “comprising” for the composition followed by “consisting of” for “an interactive two component system” followed by another “comprising” when “optionally” defining the crosslinking component that is within the two component system that was closed with “consisting of”. This change in transition phrases makes it unclear how and what the composition is open and closed to. For the purpose of compact prosecution, if the prior art teaches a composition for a system that has a targeting component and a crosslinking component, then it will read on the claim.
Claims 2-18 are withdrawn as being dependent on an indefinite claim without repairing the issue of indefiniteness.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “crosslinking component”, and the claim also recites “optionally wherein the crosslinking component comprises a dendrimer, a star polymer, a polyelectrolyte or a nanoparticle”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note that in this case, “optionally” is not necessarily being used as an “or” and is not used in the form A, B and optionally C, where the C ingredient is not needed, but rather to introduce narrower instances of crosslinking component, where it is unclear if applicant wants these narrower forms to be required for consideration of the claim limitation. Applicant may either delete “optionally” or delete the entire recitation starting from “, optionally” and make a new dependent claim that indicates “…wherein the crosslinking component is in the form of a dendrimer, a star polymer, a polyelectrolyte or a nanoparticle.” For the purpose of compact prosecution, the crosslinking component in claim 1 will be considered if it is any form/type in the prior art.
Claims 2-18 are withdrawn as being dependent on an indefinite claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 15 recites the broad recitation “small molecule crosslinker or polymeric crosslinker”, and the claim also recites “optionally wherein the small molecule crosslinker or polymeric crosslinker is bivalent or multivalent”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note that in this case, “optionally” is not necessarily being used as an “or” and is not used in the form A, B and optionally C, where the C ingredient is not needed, but rather to introduce narrower instances of crosslinking component, where it is unclear if applicant wants these narrower forms to be required for consideration of the claim limitation. Applicant may either delete “optionally” or delete the entire recitation starting from “, optionally” and make a new dependent claim that indicates “…wherein the small molecule crosslinker or polymeric crosslinker is bivalent or multivalent.” For the purpose of compact prosecution, the small molecule crosslinker or polymeric crosslinker” in claim 1 will be considered if it is any form/type in the prior art.
Claims 16-17 are rejected as being dependent on indefinite claims.
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.
Claim 4, 7, 12 and 15 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. Claims 4, 7, 12 and 15 all provide for “targeting component” then use “comprise(s)” or “further comprise(s)” to provide a limitation to the targeting component when the targeting component is found in claim 1 to be in “an interactive two-component system consisting of a targeting component and a crosslinking component”. “Consisting of” denotes that the system is closed to other components. Thus, it appears that claims 4, 7, 12 and 15 would open up this closed system from claim 1, on which claims 4, 7, 12 and 15 directly or indirectly depend, to other components of the prior art. 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.
Claims 4 and 6 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. Claims 4 and 6 provide for “a polypeptide sequence comprises” where the polypeptide sequence is a part of the targeting component found in claim 1 to be in “an interactive two-component system consisting of a targeting component and a crosslinking component”. “Consisting of” denotes that the system is closed to other components. Thus, it appears that claims 4 and 6 would open up this closed system from claim 1, on which claims 4 and 6 indirectly depend, to other components of the prior art due to “a polypeptide comprises”. 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 10 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 10 provides for “hydrophobic component comprises” where the hydrophobic component is a part of the targeting component found in claim 1 to be in “an interactive two-component system consisting of a targeting component and a crosslinking component”. “Consisting of” denotes that the system is closed to other components. Thus, it appears that claim 10 would open up this closed system from claim 1, on which claim 10 indirectly depends, to other components of the prior art due to “hydrophobic component comprises”. 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.
Claims 11-15 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. Claims 11-15 provide for “crosslinking component comprises”, “corresponding moiety…. comprises”, and “bioorthogonal click-crosslinking group comprises” where the corresponding moiety and bioorthogonal click-crosslinking group are a part of the crosslinking component found in claim 1 to be in “an interactive two-component system consisting of a targeting component and a crosslinking component”. “Consisting of” denotes that the system is closed to other components. Thus, it appears that claims 11-15 would open up this closed system from claim 1, on which claims 11-15 directly or indirectly depend, to other components of the prior art due to “comprises” being used for crosslinking component and its parts in claims 11-15. 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 16 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 16 provides for “the nanoparticles comprise” where the nanoparticles are a part of the crosslinking component and targeting component found in claim 1 to be in “an interactive two-component system consisting of a targeting component and a crosslinking component”. “Consisting of” denotes that the system is closed to other components. Thus, it appears that claim 16 would open up this closed system from claim 1, on which claim 16 indirectly depends, to other components of the prior art due to “comprises” being used for the nanoparticles. 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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-9, 11-12, and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pourcelle et al (Biomacromolecules, Nov 2007, volume 8, pages 3977-3983).
Pourcelle teaches PCL-PEG based nanoparticles grafted with GRGDS peptide (Tables 1 and 3 and title, PCL-PEG-g-GRGDS). Pourcelle provides for an 4-(p-Azidophenyl)-N-succinimidyl butanoate (bioorthogonal group/reagent) that attaches to the copolymer (Scheme 1). Pourcelle teaches solubilizing PCL-PEGs with molecular clip in creating the version of the PCL-PEG that has the functional group that links to GRGDS when immersed with the GRGDS (page 3977, polymer chemistry and Conclusion). Therefore, GRGDS remains separate from the linkable/activated PCL-PEG until they are immersed together. Pourcelle teaches the preparation of the nanoparticles on page 3981. Pourcelle also provides for PLGA and PLGA-PEG for the nanoparticles (page 3981). PCL is hydrophobic and PEG is hydrophilic. Pourcelle teaches hydrolytically degradable polyesters (first column page 3980). Pourcelle teaches average nanoparticle sizes of 192 nm for the PCL-PEG-g-GRGDS-2 (table 2). The conclusion of Pourcelle indicates that it is confirmed that the targeting is due to the RGD sequence and not just the nature of the particles. Pourcelle teaches “Nanoscopic particles self-assembled from amphiphilic block copolymers have been developed over the past years for the preparation of various drug delivery systems. The biodegradable carriers made of polyethylene glycol (PEG)-polyester diblock copolymers emerged as the most adequate devices due to their prolonged circulation half-life in blood, their ability to bypass natural barriers, their reduced rate of uptake by liver, and their controllable delivery potientiality” (page 3977).
Claim(s) 1-3 and 11-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by van Lith et al (Bioconjugate Chemistry, 2017, volume 28, pages 539-548).
The targeting component is not indicated to not allow crosslinking portions and the crosslinking component is not indicated to not have targeting. Thus, as long as the prior art teaches two components where at least one has targeting and at least one other separately has a crosslinking ability, then it will read on the limitation.
van Lith teaches PEGylation of an antibody and then addition of an azide group while also addition of DBCO onto a nanoparticle (abstract). This offers a click chemistry where the antibody can be crosslinked to the nanoparticle. Thus, both the azide-PEG-antibody and the DBCO-nanoparticle can act as crosslinking components and the antibody portion can act as a targeting component. The abstract notes that the DBCO or azide can be used on either part. This strategy is also noted in figure 6. van Lith notes that PEGylation is also important on nanoparticles and notes PCL-mPEG diblock micelles (first column of 544). Here, resulting micelle particles are 28 nm (page 544). van Lith teaches the bioorthogonal site-specific conjugation (conclusion). van Lith notes the potential for making targeted nanoparticles (conclusion). Since van Lith teaches the components separate until the linking occurs, it recognizes the two component system. van Lith teaches making antibodies with the click moieties and also making Ben-PCL7-PEG2000-DBCO to also make them clickable (pages 545-546).
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.
Claims 10 in addition to claims 1-9, 11-12, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Pourcelle et al (Biomacromolecules, Nov 2007, volume 8, pages 3977-3983).
Pourcelle teaches as discussed above and teaches both PCL-PEG and PLGA-PEG, but does not explicitly teach a version with linking portion bound to PLGA-PEG.
Pourcelle teaches the preparation of the nanoparticles on page 3981. Pourcelle also provides for PLGA and PLGA-PEG for the nanoparticles (page 3981). PCL is hydrophobic and PEG is hydrophilic. Pourcelle teaches hydrolytically degradable polyesters (first column page 3980).
One of ordinary skill in the art before the time of filing would have seen the PEG groups on the PLGA (another polyester), which are also part of the nanoparticle as suitable groups for adding a linking moiety. As the PEG group is important for addition of this linker, the PEG-PLGA would be seen as another portion of the nanoparticle to add the linking group with a reasonable expectation of success in following a similar procedure to achieve it.
Claims 13 and 14 in addition to claims 1-10, 11-12, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Pourcelle et al (Biomacromolecules, Nov 2007, volume 8, pages 3977-3983) and van Lith et al (Bioconjugate Chemistry, 2017, volume 28, pages 539-548).
Pourcelle teaches the claims as discussed above.
Pourcelle does not teach using the linking system with DBCO or azide.
van Lith teaches attaching PEG on molecules to either azide or DBCO so that alkyne-azide cycloaddition can be used to connect molecules (abstract, also figure 3). This would allow the crosslinker component on the PEG portion of a molecule. van Lith provides for an approach to prepare molecularly defined targeted nanoparticles with preserving targeting potential and removing unwanted tags (conclusion).
One of ordinary skill in the art before the time of filing would have seen use of azides and/or DBCO of van Lith as suitable approaches to link/click molecules together and that these groups can be attached to PEG groups in a molecule for linking to other molecules as in teachings of Pourcelle. As van Lith notes its approach aids to prepared targeted nanoparticles with preserving targeting potential, a person of ordinary skill in the art with the teachings of Pourcelle would be motivated to use such a strategy to link the GRGDS for targeting to copolymer nanoparticles with a reasonable expectation of better preserving targeting ability.
Claim 18 in addition to claim 1-3 is rejected under 35 U.S.C. 103 as being unpatentable over Pourcelle et al (Biomacromolecules, Nov 2007, volume 8, pages 3977-3983) and Lee WO 2021125805A1.
Pourcelle teaches the claims as discussed above.
Pourcelle does not teach the packaged product of claim 18 where items are kept separate until use.
Lee teaches “a first chamber containing an amphiphilic block copolymer, a cationic compound, and a polylactate; and A second chamber containing an active ingredient selected from a nucleic acid, a polypeptide, a virus, or a combination thereof; A kit for preparing a nanoparticle composition” (claims and abstract). Lee provides for preparation of the nanoparticles by mixing of the components (abstract). As Lee teaches the components in two chambers, it is construed as a two part system. Lee teaches “It is an object of the present invention to easily form drug-containing nanoparticles by simply mixing the kit components so that it is easy for the end consumer to use, and drug-containing nanoparticles can be easily formed immediately before use” (Description in English translation).
One of ordinary skill in the art before the time of filing would have provided the separate agents of Pourcelle (peptide portion and copolymer portion) as separate components to be combined before use by the teachings of Lee which provides for a two chamber system to simply mix and form the nanoparticles before use. There would be a reasonable expectation of success to form kits from materials to be conjugated to form targeted nanoparticles by the combined teachings of Pourcelle and Lee.
Conclusion
No claims are allowed.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613