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 .
This is the First Office Action on the Merits of US application 17/798,868 filed on 08/10/2022 which is a 371 of PCT/US2021/017809 filed on 02/12/2021 which claims US priority benefit of US Provisional 62/975,479 filed on 02/12/2020.
The most recent filing receipt was filed on 12/27/2022.
Claims 28-34 are cancelled. Claims 1-27 and 35 are pending.
Claims 27 and 35 are withdrawn.
Claims 1-26 are under examination.
Election/Restrictions
Applicant’s election without traverse of invention Group I (e.g., claims 1-26) and of the species: “a combination of Val for X1 of SEQ ID NO:1 and Ala for X2 of SEQ ID NO:12, in the reply filed on August 29, 2025 is acknowledged.
Claims 27 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 29, 2025.
Information Disclosure Statement
The IDS statements filed on 10/28/2025, 08/04/2025, 02/17/2025, 10/02/2024, 07/03/2024, 03/29/2024, 07/20/2023, 04/30/2023, 02/02/2023, and 01/04/2023 have been considered by the examiner. Note that the IDS statements filed on 10/28/2025 and 08/04/2025 have checked the box indicating No IDS size fee is required at this time under 37 CFR 1.17(v).
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.
Claims 1-26 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 recites the limitation "the amino acids" in line 12. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites an amino acid sequence in lines 2-3 and in line 8, and recites a polyalanine domain in line 11. It is unclear what amino acid structure of the claims is referred to as "the amino acids" in line 12.
Claim 2 recites the limitation "the amino acids" in line 13. There is insufficient antecedent basis for this limitation in the claim. Claim 2 recites an amino acid sequence in lines 3-4 and in line 9, and recites a polyalanine domain in line 12. It is unclear what amino acid structure of the claims is referred to as "the amino acids" in line 13.
Claims 3-25 are indefinite for the same reasoning as they depend from claim 2 and are not remedial.
In claim 3 recites the limitation “a first assembly including one of the disordered polypeptide and the POP; and a second assembly including the other of the disordered polypeptide and the POP” in lines 2-3. There is insufficient antecedent basis for the terms “one of” and “the other of” in this limitation because claim 3 depends from base claim 2 which recites “a disordered polypeptide” in the singular in line 3 and recites a “POP” in the singular in line 6. The terms “one of” and “the other of” appear to intend a plurality.
Regarding claim 14, the limitation “wherein the polypeptides self-assemble into the assembly in two phases” appears to intend an active method step of self-assembly. It is unclear if the scope of the claim intends to require such self-assembly method steps. Claim 14 is drawn to a product as it depends from base claim 2 which is drawn to a product composition comprising an assembly of polypeptides.
In addition, claims 19-21 are indefinite because they depend from claim 14 and are not remedial.
Claim 26 recites the limitation "the amino acids" in line 10. There is insufficient antecedent basis for this limitation in the claim. Claim 26 recites an amino acid sequence in line 6 and a polyalanine domain in line 9. It is unclear what amino acid structure of the claims is referred to as "the amino acids" in line 10.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims are drawn to a composition comprising a “disordered polypeptide” having a transition temperature and a partially ordered polypeptide (POP) having a transition temperature of heating and of cooling. The POP comprises a plurality of disordered domains and a plurality of structured domains. The “disordered polypeptide” and the POP have a functional requirement where the disordered polypeptide’s transition temperature is at least +/- 1° C compared to the POP’s transition temperature of heating.
Thus the claims require the critically essential element of corresponding structures of the disordered polypeptide and the POP each having specific transition temperature properties to meet this functional requirement.
The state of the art shows that compositions comprising disordered polypeptides comprising the pentameric repeat (VPGX1G)m and (VPGX2G)n of the present claims were known. However, the state of the art shows that species having the required transition temperature properties were unpredictable and particularly dependent on amino acid sequence, structure, and reaction conditions. See Aladini et al “Chemical synthesis and characterization of elastin-like polypeptides (ELPs) with variable guest residues” (Journal of Peptide Science 2016 Vol 22, No 5, pages 334-3342, epub March 22, 2016). Also, see Bae et al in “Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin” (Journal of Controlled Release” 2007 Vol 122, pages 16-23).
The state of the art discloses that the transition temperature depends on the precise structure of the pentameric repeat (VPGX1G)m and (VPGX2G)n of the present claims. For example, Aladini et al discloses that changing a guest residue from a Val (valine) to a Leu (leucine) has a large effect on the disordered polypeptide. Note that valine is a nonpolar, hydrophobic amino acid and is one of three branched-chain amino acids (including isoleucine, leucine) which have similar structures and share common transport and metabolic pathways. Despite these similarities, as a guest residue in a (VPGX1G)m and/or (VPGX2G)n sequence of a disordered polypeptide, this simple amino acid substitution results in very different transition phase temperature properties (See graph below). Further, the state of the art discloses that the added structured domains also effect the transition temperature. In addition, the state of the art discloses that the transition temperature is directly affected by the reaction conditions. Aladini et al recite:
Substituting valine with isoleucine lowers the transition temperature by almost 20 K. This indicates the contribution of hydrophobic side chain interaction of the guest residues in elastin-like polypeptide aggregation. However, as demonstrated previously, we also did not find any change in secondary structure when measuring CD 22. Although there is no notable difference between the hydrophobicity of leucine and isoleucine 17, ELP[I3L2-10] aggregated at a lower Tt than ELP[I-10] and by replacing just four isoleucines with leucine residues in the whole peptide Tt was lowered again by 7 K. This finding implicates that besides the general hydrophobicity, steric effects of linear and branched side chains have an impact on the phase transition of ELPs. In ELP[A1L4-10], as Ala is less hydrophobic than leucine, the solubility of the ELP is increased and this helps with solubilizing the ELP during the reverse cooling process. All synthetic ELPs with Tt values between 25 and 70 °C can undergo the ITC at least 6 times without loss of peptide (Figure 2C).
See especially Figure 2 A-F & legend of Aladini et al:
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The instant specification states that because the disordered polypeptides and the POPs “can have tailored transition temperatures, their thermal responsiveness can be used to form unique protein-based structures.” The specification discloses methods of making embodiments of the claimed compositions and testing whether such embodiments possess the required transition temperature properties. However, the specification does not show a representative set of species of such structures so that one of ordinary skill in the art would have been able to envision/predict whether a given prophetic embodiment would possess such required transition temperature properties. See Example 2, paragraphs 00111-00113. Example 2 uses a species where the “guest residue” of the (VPGX1G) sequence is a Val and the polyalanine is A4 and is 25% of the structure. Example 2 results are shown in Figures 1D-E, 6 and 7.
However, the present claims are broad to where the guest residue is any amino acid other than proline. The elected species for the presently claimed invention are to a combination of where the guest residue in the disordered polypeptide is Val (valine) and the guest residue in the POP is Ala (alanine). Further, the present claims are broad to where the polyalanine domain comprising at least 5 alanine residues. Dependent claim 10 specifies a polyalanine comprising 25 alanine residues. However, the Example provided in the specification is a polyalanine having four alanine residues and not the combination of Val and Ala as required by the claims.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
To satisfy the written description requirement, MPEP §2163 states, in part “...a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.” Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “...disclosure of relevant, identifying characteristics, 1.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.”
The limited disclosure of the specification in view of the vast genus of polypeptides encompassed by the claims does not adequately describe the entire genus of molecules encompassed by the claims.
“Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that the inventor(s) invented what is claimed.” (See Vas-Cath at page 1116).
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eh Lily & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) (‘In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. ..."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
The court and the Board have repeatedly held (Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,18 USPQ2d 1016 (CA FC, 1991); Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993); Fiddes v. Baird, 30 USPQ2d 1481 (BPAI 1993) and Regents of the Univ. Calif. v. Eh Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)) that an adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the nucleic acid itself.
Thus, one of skill at the time of the invention could not have concluded that the inventor(s) were in possession of the genus of compositions of combinations of disordered and partially disordered polypeptides having the required functional properties regarding transition temperatures.
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 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over Bae et al in “Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin” (Journal of Controlled Release” 2007 Vol 122, pages 16-23), in view of Aladini et al “Chemical synthesis and characterization of elastin-like polypeptides (ELPs) with variable guest residues” (Journal of Peptide Science 2016 Vol 22, No 5, pages 334-3342, epub March 22, 2016), in view of Park et al (US2013/0197359”), in view of WO-2019/006374 to Chilkoti et al (WO-2019006374-A1 published January 3, 2019).
Regarding independent claims 1, 2, and 26, Bae et al discloses nanoparticles comprising an assembly of polypeptides, wherein the polypeptides comprise:
a disordered polypeptide having a transition temperature (Tt) and comprising an amino acid sequence of [VPGVG]m (SEQ ID NO: 1), specifically where the “guest residue X1 is the elected species of Val and
a second polypeptide having a transition temperature of heating (Tt-heating) and a transition temperature of cooling (Tt-cooling), and comprising a plurality of partially ordered domains, wherein each disordered domain includes an amino acid sequence of [VPGAG]n (SEQ ID NO: 12), specifically where the “guest residue X2 is the elected species of Ala. Further, Bae et al disclose that the pentameric repeat sequence VPGXaaG is in a composition of 60 repeats with guest residues as valine, alanine and glycine in a 5:2:3 ratio at the ‘Xaa’ position. Thus, the composition of Bae et al contains VPGVG where m is 30, and VPGAG where n is 12. (See Abstract). Thus Bae et al meets the limitation of where m is 10 to 500 and where n is 1 to 200.
Further, regarding independent claims 1, 2, and 26, Aladini et al disclose compositions comprising an assembly of polypeptides, where the polypeptides comprise: a disordered polypeptide comprising the pentameric repeat amino acid sequence (VPGVG)m, where m is 10 (see Table 1, line 1). Aladini et al disclose a transition temperature (see Fig 2A). Aladini et al disclose a partially ordered polypeptide comprising the amino acid sequence (VPGAG)n, where n= 1 to 200; having a transition temperature of heating and of cooling, where the disordered polypeptide’s transition temperature is at least + 1°C compared to the POP's Tt-heating. (See Abstract; Fig2B and legend). Note that the graph of Fig2B shows a composition of (VPGAG)m and (VPGLG)m, (where m is 10) rather than a combination of (VPGAG)m and (VPGVG)m for the presently elected species. The nomenclature for the Aladini et al reference is as follows:
The capital letters inside the bracket are the single letter amino acid codes that indicate the guest residues in the ELP sequence, and the subscripts specify the number of Val-Pro-Gly-Xaa-Gly repeats with each corresponding guest residue. The total number of pentapeptides (VPGXG) is designated by n. For instance, ELP[A1L4-10] is an ELP of 10 repeats of pentapeptide in length, which has a repeat unit consisting of five pentapeptides with the guest residues Ala and Leu in a 1 : 4 ratio, respectively.
Thus, Aladini et al discloses the “disordered polypeptide having a transition temperature” of the presents claim with the elected species of Ala, specifically (VPGAG)n, where n is 10 (meeting limitation of n= 1 to 200); and a combination of (VPGAG)n and (VPGLG)m (where n and m are each 10 (meeting the limitation of the A substitution of Val for Leucine is obvious for rationale that Aladini et al suggests substitution between such hydrophobic amino acids. Note that valine is a nonpolar, hydrophobic amino acid and is one of three branched-chain amino acids (including isoleucine, leucine) which have similar structures and share common transport and metabolic pathways. (See abstract.)
Aladini et al disclose that the polypeptides comprise the pentameric repeat (Val-Pro-Gly-Xaa-Gly) containing different guest residues Xaa, derived from mammalian elastin. (See abstract.) The temperature-dependent aggregation and disaggregation of ELPs is controlled by composition of the pentameric repeats as well as the number of repetitive units within the ELP. External parameters such as ELP concentration, pH, and most importantly, salt effects heavily influence the transition temperature. (See abstract.) Aladini et al a series of 51mer peptides consisting of 10 pentameric ELP repeats with hydrophobic as well as charged guest residues such as isoleucine, leucine, alanine, lysine, and/or glutamate. The structure of 10 pentameric ELP repeats meets the limitation of where m= 10 to 500 and where n= 1 to 200.
Aladini et al states that “These guest residues expand the available toolbox of synthetic ELPs and provide ELPs that can be chemically modified and tuned to specific environments”. (See abstract).
Further, regarding independent claims 1, 2, and 26, Park et al disclose regarding disclose a composition comprising lipid nanoparticles comprising an elastin-like disordered polypeptide conjugated to one or more hydrophobic moieties, the disordered polypeptide having a transition temperature, where the lipid molecule has a phase transition temperature within a range from about 39 degree C to about 60 degree C and comprising an amino acid sequence (VPGX1G)m (i.e., instant SEQ ID NO: 1), where X1 is any amino acid except proline and m is 10 to 500 (See Abstract, “Solid lipid nanoparticles (SLNs) including elastin-like polypeptides"; ref claims 1 & 5; para 0022, 0037). Park et al discloses the “guest residue” to be an Ala (alanine) with m being 2 to 200. (See ref SEQ ID NO:7 and para 0022 showing a transition temperature of heating and cooling. Further Park et al a partially ordered polypeptide (POP) having a transition temperature of heating (Tt- heating) and a transition temperature of cooling (Ti-cooling), and comprising a plurality of disordered domains, wherein each disordered domain includes an amino acid sequence of [VPGX2G]n (SEQ ID NO: 12), wherein X2 is any amino acid except proline and n is 1 to 200, and a plurality of structured domains. (see entire document). For example, Park et al discloses domains that include a polyalanine domain stating: “and may include another portion in a molecule, for example, one or more amino acids such as alanine…between the repeating units, and/or at either end of the ELP” (para 0027).
Thus, the references of Bae et al, Aladini et al, and Park et al disclose the identical disordered polypeptide comprising pentameric repeat sequences of the present base claims 1, 2, and 26 and the Park et al reference suggest including a plurality of structured domains comprising a plurality of alanines between the repeating units. However, the references of Bae et al, Aladini et al, and Park et al differ from the present claims because they do not expressly teach the partially ordered polypeptide comprising a plurality of structured domains, wherein each structured domain includes a polyalanine domain, the polyalanine domain comprising at least 5 alanine residues and having at least about 50% of the amino acids in an alpha helical conformation, wherein the disordered polypeptide's Tt is at least +/-1°C compared to the POP Tt heating.
Chilkoti et al discloses a partially ordered polypeptide (POP) (see para 000144) comprising a polyalanine domain, the polyalanine domain comprising at least 5 alanine residues and having at least about 50% of the amino acids in an alpha helical conformation, that meets the limitation that the disordered polypeptide's Tt is at least +/-1°C compared to the POP's Tt heating. Chilkoti et al recites:
Combinations of order and disorder have also been explored in the field of synthetic polymers. Ratios of atactic (disordered) and isotactic (ordered) polymer blocks have been used as a means to control gelation and thermo-responsive phase transitions. ... peptide polymers are attractive for biotechnology and biomedical applications because of their biocompatibility and our ability to design absolute molecular levels through recombinant synthesis.
Also, see especially ref claims 1, 7, and 16:
Claim 1 - “A partially ordered polypeptide (POP) comprising: a plurality of disordered domains; and a plurality of structured domains, wherein the POP exhibits phase transition behavior.") comprising a polyalanine domain, the polyalanine domain comprising at least 5 alanine residues and having at least about 50% of the amino acids in an alpha-helical conformation (Claim G(ii) - "polyalanine domain, each polyalanine domain comprising at least 5 alanine residues and having at least about 50% of the amino acids in an alpha-helical conformation,";
Claim 7 - "The polypeptide of claim 8, wherein the structured domain comprises a polyalanine domain.”), and further discloses wherein the disordered polypeptide's Tt is at least +/- 1 deg C compared to the POP's Tt-heating
(Claim 16 - “wherein the transition temperature of heating (Tt- heating) is greater than the transition temperature of cooling (Tt-cooling)."; para [00085] - “The POP may phase transition at a variety of temperatures. The POP may have a transition temperature from about 0 degree C to about 100 degree C").
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to include a POP comprising a structured domain comprising a polyalanine domain of Chilkoti et al in the POP structures and polypeptide assemblies of either of Bae et al, Aladini et al, or Park et al for the rationale to improve functional properties of the composition comprising disordered polypeptides such as for controlling gelation and thermo-responsive phase transitions.
It would have been obvious to combine the elements of the cited references because Park et al suggest a partial disordered polypeptide including a plurality of structured domains comprising a plurality of alanines between the repeating units and Chilkoti et al state that combinations of order and disorder have also been explored in the field of synthetic polymers are attractive for biomedical applications. Chilkoti et al state that “[r]atios of atactic (disordered) and isotactic (ordered) polymer blocks have been used as a means to control gelation and thermo-responsive phase transitions” and “peptide polymers are attractive for biotechnology and biomedical applications because of their biocompatibility and our ability to design absolute molecular levels through recombinant synthesis” para 0144). Further, the cited references because they are in the same field of making disordered polypeptides for attaching to proteins of interest and using phase transition properties of the polypeptide compositions.
Absent evidence to the contrary it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to attach structured domains containing a polyalanine to the pentameric-containing disordered polypeptides to result in partially disordered polypeptides having different transition temperatures to arrive at the presently claimed invention.
Further, regarding claim 3, Park et al discloses nanoparticle assemblies which are construed to meet the limitation of a first assembly including one of the disordered polypeptide and the POP; and a second assembly including the other of the disordered polypeptide and the POP, wherein at least a portion of the first assembly contacts at least a portion of the second assembly. (See para 00134, 0070, 0079). Further, regarding claim 3, Chilkoti et al disclose the presence of bundled helices within the POP assemblies” (see para 00134).
Regarding claim 4, Aladini et al discloses that the Tt is about 10 °C to about 70 °C. Aladini et al state that “transition temperatures of all synthetic ELPs and the fusion construct were determined by measuring turbidity in solution and spanned a large temperature range between 25 and 70 °C, providing synthetically accessible ELPs with transition temperatures suitable for in vitro and in vivo applications”. (See abstract). Further, regarding claim 4, Park et al disclose that the Tt is about 10 °C to about 70 °C (see para 0022).
Regarding claim 5, Aladini et al discloses that the Tt- heating and the Tt-cooling are both individually about 10 °C to about 70 °C. Aladini et al state that “transition temperatures of all synthetic ELPs and the fusion construct were determined by measuring turbidity in solution and spanned a large temperature range between 25 and 70 °C, providing synthetically accessible ELPs with transition temperatures suitable for in vitro and in vivo applications”. (See abstract). Further, regarding claim 5, Park et al disclose that the Tt is about 10 °C to about 70 °C (see para 002, 0044).
Regarding claim 6, Aladini et al discloses that the Tt-heating is at least + 5°C compared to the Tt-cooling. (See Fig2). Further, regarding claim 6, Chilkoti et al disclose that the Tt-heating is at least + 5°C compared to the Tt-cooling. (See ref claim 16; para 0085).
Regarding claim 7, Aladini et al discloses that X1 and X2 are both individually Val, Ala, or a combination of Val and Ala. (See Abstract, entire article). Further, Park et al disclose that X1 and X2 are both individually Val, Ala, or a combination of Val and Ala. (See para 0036-0037; ref SEQ ID NOs 6 & 7)
Regarding claim 8, Aladini et al discloses that m is 20 to 200. (See Abstract). Further, Park et al disclose that m is 20 to 200 (see para 0037).
Regarding claim 9 Aladini et al discloses the structure of 10 pentameric ELP repeats which meets the limitation of where n is 5 to 50. (See abstract.) Further, Park et al disclose that n is 5 to 50 (see para 0037).
Regarding claim 10, Chilkoti et al discloses that the structured domain comprises an amino acid sequence of (A)25 (SEQ ID NO:15). (See Chilkoti et al ref claim 10).
Regarding claim 11, Chilkoti et al discloses that the structured domain is present at about 4% to about 75% of the POP based on total number of amino acids. (See Chilkoti et al ref claim 12).
Regarding claim 12, Aladini et al disclose that the disordered polypeptide, the POP, or both comprise a crosslinking moiety. Aladini et al recite that the guest residues expand the available toolbox of synthetic ELPs and provide ELPs that can be chemically modified and tuned to specific environments. Specifically, an N-terminal cysteine is added allowing disulfide-based crosslinking of ELPs and to link synthetic ELPs to a recombinantly produced protein using native chemical ligation. Specifically, an “N-terminal cysteine is added allowing disulfide-based crosslinking of ELPs and to link synthetic ELPs to a recombinantly produced protein using native chemical ligation”. (See abstract). Further, Chilkoti et al disclose that the assembly includes crosslinks between the polypeptides. (See para 0043; 0079.)
Regarding claim 13, Aladini et al discloses that an N-terminal cysteine is added to the ELPs. Although Aladini et al suggests using this cysteine to allow disulfide-based crosslinking, this cysteine also meets the claim limitation of a crosslinking moiety comprising a UV crosslinkable amino acid derivative because an N-terminal cysteine is capable of UV crosslinking. Further, Chilkoti et al disclose that the assembly includes crosslinks between the polypeptides. (See para 0043; 0079.)
Regarding claims 14, and 19-21, note that the process by which a process is made is not generally afforded patentably weight for purpose of applying prior art. Thus claims 14 and 19-21 are construed to be rendered obvious for same reasoning as claim 2. Furthermore, Park et al disclose self-assemblies of disordered polypeptides. Regarding claim 20, Park et al discloses the assembly comprises: (i) a porous network including the POP. Regarding claim 21, Park et al discloses a particle wherein the assembly comprises: a porous network including the POP. (See para 0023, Abstract). In addition, Chilkoti et al disclose that the polypeptides self-assemble into an assembly in two phases (See para 0086-87)
Regarding claim 15, Chilkoti et al discloses wherein the assembly comprises:
a porous network including the POP (see para 0140); and
a plurality of particles contacting the network, each particle including the disordered polypeptide (see para 00140).
Regarding claim 16, Park et al discloses wherein the assembly comprises a plurality of particles, each particle comprising: a core including the disordered polypeptide; and a shell including the POP, wherein the shell is positioned on a surface of the core. (See para 0023,0069, 0017, 0125).
Regarding claim 17, Chilkoti et al discloses that the assembly comprises:
a porous network including the POP and a plurality of particles contacting the network, each particle including the disordered polypeptide. (see para 0140; Fig 26)
Regarding claim 18, Chilkoti et al discloses a particle wherein the assembly comprises a network of network particles. (See para 00140; Fig 26). Further, Park et al disclose that each network particle comprises a core including the disordered polypeptide, and a shell including the POP, wherein the shell is positioned on a surface of the core. (See Park et al Abstract; para 0069, 0017, 0125).
Regarding claim 22, Chilkoti et al disclose that the assembly includes crosslinks between the polypeptides. (See para 0043; 0079.)
Regarding claim 23, Chilkoti et al disclose a drug molecule encapsulated in the assembly, the first assembly, or the second assembly. (See para 0012; 0096.)
Regarding claim 24, Chilkoti et al discloses that the drug molecule comprises a small molecule, a polypeptide, a polynucleotide, a lipid, a carbohydrate, or a combination thereof. (See para 0012; ref claim 47.)
Regarding claim 25, Chilkoti et al discloses a cellular scaffold comprising a composition of biocompatible polypeptides. The nanoparticles meet the limitation of a cellular scaffold and a plurality of cells. (See para 0094; 00181-182.)
Regarding the limitations of dependent claims 3-25, one of ordinary skill in the art would have been motivated to modify the compositions rendered obvious over Bae et al, Aladini et al, and Park et al in view of Chilkoti et al to include the specific elements recited just above as disclosed in the references of Aladini et al, Park et al, and Chilkoti et al regarding the POP structures and polypeptide assemblies for the rationale to improve functional properties of the compositions comprising disordered polypeptides such as for controlling gelation and thermo-responsive phase transitions and to put the compositions and assemblies for use in biomedical applications as suggested by Chilkoti et al. For example, Chilkoti et al state that combinations of order and disorder have also been explored in the field of synthetic polymers are attractive for biomedical applications. Chilkoti et al state that “[r]atios of atactic (disordered) and isotactic (ordered) polymer blocks have been used as a means to control gelation and thermo-responsive phase transitions” and “peptide polymers are attractive for biotechnology and biomedical applications because of their biocompatibility and our ability to design absolute molecular levels through recombinant synthesis” (para 0144).
It would have been obvious to do such because the cited references are in the same field of making disordered polypeptides for attaching to proteins of interest and using phase transition properties of the polypeptide compositions.
Absent evidence to the contrary it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to attach structured domains containing a polyalanine to the pentameric-containing disordered polypeptides to result in partially disordered polypeptides having different transition temperatures to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action:
Lu et al (US2016/0220727).
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658