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 1-8, 17, 18, 23-25, and 36, and the species RAGE as the target (SEQ ID NO: 9) as well as glutamine as the therapeutic target in the reply filed on 3/14/2025 is acknowledged.
Claims 37, 43, 49, 50, and 58 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected invention groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/14/2025.
Priority
Priority to US 62/968,919, filed 1/31/2020, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 3/18/2024, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1-8, 17, 18, 23-25, 34, and 36 are under examination. Claims 37, 43, 49, 50, and 58 are currently withdrawn from examination.
Claim Interpretation
Regarding claim 1, the charged peptide segment is comprised of peptide bonds and therefore the targeting moiety is covalently attached to the β-sheet-forming peptide segment, because peptide bonds are covalent bonds.
Claim Rejections - 35 USC § 112
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 7, para. 5, filed 1/15/2026, with respect to rejection under 112(a) have been fully considered and are persuasive. The rejection of claim 3 has been withdrawn.
Examiner Note: The specification states: “"Sequence identity" or "identity" in the context of two polypeptide sequences makes reference to the residues in the two sequences that are the same when aligned for maximum correspondence over a specified comparison window.” (Specification, para. [0067]).
This rejection is withdrawn because even in the largest claimed peptide, SEQ ID NO: 2, a single mutation yields only 12/13 = 92.3% identity, which falls short of the amended identity of 95%. Consequently, this rejection is withdrawn because the genus sizes have be reduced to encompass only sequences that possesses the claimed sequences because any substitutions in this specified comparison window would result in a sequence identity less than 95%.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive.
Maintained Rejections
Claims 1, 2 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025).
Regarding claim 1, Kibbe discloses a peptide amphiphile comprising: (a) a hydrophobic non-peptidic segment; (b) a β-sheet-forming peptide segment; (c) a charged peptide segment; (d) a targeting moiety, wherein the targeting moiety comprises a binding sequence for a target protein; and (e) a therapeutic agent, wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet-forming peptide segment, wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment, and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety (Claim 1).
Instant claim 1 recites “wherein the charged peptide segment is covalently attached to the targeting moiety.” From the Kibbe disclosure, the charged peptide segment is located between β-sheet-forming peptide segment and the targeting moiety (Claim 1). Consequently, the charged peptide segment is also a linker between the β-sheet-forming peptide segment and the targeting moiety and therefore the targeting moiety is covalently attached to the β-sheet-forming peptide segment. Under this interpretation of the claims, Kibbe fulfills the recited limitation found in Applicant’s claim 1.
Even if Kibbe did not disclose that the β-sheet-forming peptide segment is covalently attached to the targeting moiety, it would have been prime facie obvious to attach the subcomponents of the peptide amphiphile of Kibbe to arrive at the peptide amphiphile of claim 1. In the present case, a person of ordinary skill in the art would know that the subcomponents of the peptide amphiphile can be rearranged with respect to each other to create new peptide amphiphiles with similar properties, each unit providing the same properties in each amphiphile. A person of ordinary skill in the art would be invoking the rationale of a simple substitution (or reordering) of one known element for another to obtain predictable results. The retention of each segment, even if different order will predictably maintain the functions of each.
Paragraph [0048] of Kibbe contemplates such a modular approach to the peptide amphiphile “Targeting moieties may direct PA structures (and therefore the therapeutics attached thereto or encapsulated therein) to specific organs, tissues, cell types, Subcellular locations (e.g., organelles), pathogens (e.g., viruses, bacteria, etc.), diseases (e.g., to cancerous cells), etc. Targeting peptides and other moieties for achieving such localization are understood.”
The peptide amphiphile of Kibbe is not specifically targeted to pulmonary tissue. However, Oczypok discloses that: “Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE’s role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia.” (Oczypok, page 40, Summary).
Furthermore, Xue discloses that two regions of the protein S100B interact with RAGE: F43, L44, E45, E49 and A78, M79, V80, T81, T82, A83, H85, E86, F87, F88, E89, and H90 (Xue, page 1513, col. 2 para. 4). In particular, A78-H90 of S100B has the sequence AMVTTACHEFFEH (Genbank Accession NP_006263).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the targeting sequence of Xue with the peptide amphiphile of Kibbe to arrive at the claimed invention. A person of ordinary skill in the art would motivated to target pulmonary tissue in order to treat disorders of the lung as described by Oczypok above (Oczypok, page 40, Summary). A person of ordinary skill in the art would also be motivated to target RAGE in order to target pulmonary tissue because it is highly expressed in pulmonary tissue as disclosed by Oczypok. (Oczypok, page 40, Summary). A person of ordinary skill in the art would have a reasonable expectation of success because Xue shows that the sequence AMVTTACHEFFEH (Genbank Accession NP_006263) interacts with the RAGE receptor. (Xue, page 1512, Figure 2). Consequently, claim 1 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 and rejected.
Regarding claim 2, claim 1 is obvious as described above. The peptide disclosed by Xue targets RAGE. Consequently, claim 2 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 and rejected.
Regarding claim 17, claim 1 is obvious as described above. Applicant claim 17 recites the peptide amphiphile of claim 1, wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment; and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety. However, Kibbe discloses a peptide amphiphile wherein: “the C-terminus of the B-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment; and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety.” (Kibbe, claim 1)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to add the limitations recited by Applicant claim 17 using the disclosed structure of the peptide amphiphile of Kibbe because the additional limitations of claim 17 are recited by Kibbe claim 1. A person of ordinary skill in the art would have a reasonable expectation of success because they are identical limitations in this case. Consequently, claim 17 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 and rejected.
Claim 3 is are rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, further in view of Marshall et al. (Marshall et al., Drug Discovery Today, 8:5, Pages 212-221, (2003)) and Fauchere et al. (Int J Pept Protein Res., 32(4):269-78 (1988)).
Regarding claim 3, claim 2 is obvious as described above. Xue discloses that two regions of the protein S100B interact with RAGE: F43, L44, E45, E49 and A78, M79, V80, T81, T82, A83, H85, E86, F87, F88, E89, and H90 (Xue, page 1513, col. 2 para. 4). In particular, A78-H90 of S100B has the sequence AMVTTACHEFFEH (Genbank Accession NP_006263). This sequence is 80% identical to SEQ ID NO: 9, because they only differ in one location. However, even if 100% identity were required, only position 84 is different, with a cysteine to alanine substitution. Position 84 is not implicated in the interaction between S100B and RAGE (Xue, page 1513, col. 2 para. 4). Furthermore, cysteine residues are removed from therapeutic proteins to reduce aggregation (Marshall, Table 1) and alanine and cysteine have a similar normalized van der Waals volume ,1.0 for Ala, 2.43 for Cys, (Fauchere, Table 1) and therefore would have similar packing effects for the interaction described in Xue. This analysis makes the substitution of alanine for cysteine at position 84 prima facie obvious before the effective filing date for a person of ordinary skill in the art, because such a person would seek to reduce aggregation for a protein therapeutic and choose to replace cysteine with a similarly sized amino acid that does not form disulfide bonds intermolecularly.
Consequently, claim 3 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263, further in view of Marshall et al. and Fauchere et al. and rejected.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, further in view of Vasileiadis et al. (Vasileiadis, et al. COPD: Journal of Chronic Obstructive Pulmonary Disease 15.2: 148-156 (2018)).
Regarding claim 4, claim 1 is obvious as described above. The combination of Kibbe, Xue, and Oczypok does not disclose targeting ACE specifically. However, Vasileiadis et al. discloses that: “ACE is an enzyme present in the circulating plasma and highly expressed in lung capillary blood vessels, which catalyzes the conversion of Ang I to Ang II (Vasileiadis, et al., page 148, col. 1, para. 3). Vasileidis also discloses: “Chronic obstructive pulmonary disease (COPD) is a complex disorder that primarily affects the lungs and is characterized not only by local pulmonary, but also by systemic inflammation which promotes the development of extrapulmonary and cardiovascular co-morbidities.” (Vasileiadis, et al., page 148, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to target the peptide amphiphile of Kibbe to ACE as disclosed by Vasileiadis. A person of ordinary skill in the art would be motivated to target pulmonary tissue to treat disorders as described by both Oczypok (Oczypok, page 40, Summary) and Vasileidis (Vasileiadis, et al., page 148, Abstract). A person of ordinary skill in the art would be motivated to target ACE because ACE is highly expressed in lung capillary blood vessels (Vasileiadis, et al., page 148, col. 1, para. 3). A person of ordinary skill in the art would have a reasonable expectation of success because Kibbe contemplates such targeting strategies: “Targeting moieties may direct PA structures (and therefore the therapeutics attached thereto or encapsulated therein) to specific organs, tissues, cell types, Subcellular locations (e.g., organelles), pathogens (e.g., viruses, bacteria, etc.), diseases (e.g., to cancerous cells), etc. Targeting peptides and other moieties for achieving such localization are understood.” (Kibbe et al., para. [0048]).
Consequently, claim 1 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263, further in view of Vasileiadis et al. and rejected.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, further in view of Vasileiadis et al. (Vasileiadis, et al. COPD: Journal of Chronic Obstructive Pulmonary Disease 15.2: 148-156 (2018)) as applied to claim 4 above, and, further in view of Guo et al. (Process Biochemistry, 63 84-95 (2017)).
Regarding claim 5, claim 4 is obvious as described above. The combination of Kibbe, Xue, Oczypok, and Vasileiadis does not disclose a peptide comprising one of SEQ NOs: 6-8. However, Guo discloses that: “Peptides RYDF, YASGR and GNGSGYVSR were obtained by
hydrolysis of the water-soluble protein of Sipuncula with pepsin and trypsin. The peptides were purified through gel filtration and reverse-phase high-performance liquid chromatography, and identified by de novo sequencing method of MALDI-TOF. All three peptides are non-competitive inhibitors of angiotensin-I converting enzyme determined by Lineweaver-Burk plots. Their inhibitory IC50 values were 235, 184 and 29 μM, respectively. ” (Guo, Abstract). Peptides RYDF and GNGSGYVSR read on SEQ ID NO: 6 and SEQ ID NO: 8, respectively.
It would have been prima facie obvious before the effective filing date of the claimed invention for a person of ordinary skill in the art to combine the amphiphilic peptide of Kibbe, Xue, Oczypok, and Vasileiadis with the sequence disclosed by Guo to arrive at the peptide claimed by Applicant claim 5. The disclosed peptides have a measured affinity for ACE and therefore a person of ordinary skill in the art would have a reasonable expectation of success of targeting ACE with the amphiphilic peptide of Kibbe, Xue, Oczypok, and Vasileiadis. Consequently, claim 5 is obvious over Kibbe et al., Xue et al., Oczypok et al., and Vasileiadis et al., further view of Guo et al., and rejected.
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015), Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, and in further view of Li et al. (Li et al., International Immunopharmacology,16,2, Pages 248-253, (2013)).
Regarding claim 6, claim 1 is obvious as described above. The combination of Kibbe, Xue, and Oczypok does not disclose a therapeutic agent. However, Li discloses that: “In summary, treatment with GLN attenuated smoke inhalation induced acute and chronic lung injury processes in rats and its protective mechanism seems to be involved in inhibiting inflammatory response and enhancing HSP expression. Accordingly, GLN could be considered as a potential therapeutic agent for preventing lung injury against smoke inhalation.” (Li, page 253, col. 1, para. 2). It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to combine the amphiphilic peptide of Kibbe, Xue, and Oczypok with a therapeutic meant for action on pulmonary tissue as disclosed by Li. A person of ordinary skill in the art would have a reasonable expectation of success because the amphiphilic peptide of Kibbe, Xue, and Oczypok is targeted to pulmonary tissue and glutamine as shown by Li to help treat several different pulmonary conditions (Li, Abstract). Consequently, claim 6 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and further view of Li et al. and rejected.
Regarding claim 8, claim 6 is obvious as described above. The therapeutic molecule described by Li et al. above is glutamine. Consequently, claim 8 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and further view of Li et al. and rejected.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kibbe (US 2015/0151002, filed 9/30/2014, published 6/4/2015), Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, further view of Li et al. (Li et al., International Immunopharmacology,16,2, Pages 248-253, (2013)) as applied to claim 6 above, and in further view of He et al. (He et al, Molecules, 24(10), 1855 (2019)).
Regarding claim 7, claim 6 is obvious as described above. The combination of Kibbe, Xue, Oczypok, and Li does not disclose a therapeutic agent wherein the therapeutic agent is attached through a covalent bond or hydrophilic/hydrophobic interaction. However, He et al. discloses that: ”Small molecule drug candidates have historically recorded a higher attrition rate in clinical
development, which partially results from suboptimal physicochemical properties. Conjugation to peptides is an approach to address poor aqueous solubility, untimely metabolism and potentially facilitate cell permeability. It has provided targeted delivery of small molecules to diseased tissue to enhance local drug concentration, and mitigate toxic effects arising from systemic exposure and accumulation in non-diseased tissues.” (He, page 3, para. 2).
He further discloses an example compound where the therapeutic agent is covalently bound: “Zoptarelin Doxorubicin (AN-152, AEZS-108, ZoptrexTM) is a peptide-drug conjugate composed of a GnRH analog and doxorubicin through an ester bond with a glutaric acid spacer.” (He, page 5, para. 2-3, Figure 2).
It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to attach the therapeutic molecule of Li to the amphiphilic peptide of Kibbe, Xue, Oczypok, and Li with the attachment scheme disclosed by He. A person of ordinary skill in the art would have a reasonable expectation of success because He discloses many such peptide-drug compositions with covalent attachments (He, Table 1). A person of ordinary skill in the art would be motivated to use an attachment scheme for the therapeutic agent of Li as described in He in order to benefit from the advantages of peptide conjugation described above. Consequently, claim 7 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and further view of Li et al. and rejected., and in further view of He and rejected.
Claims 18, 34, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Kibbe et al. (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, and, in further view of Qiu et al. (Qiu, et al., International Journal of Nanomedicine, 13, 5003–5022. (2018)) and So et al. (So et al., Adv. Biosys. 2, 1700123 (2018)) .
Regarding claim 18, claim 1 is obvious as described above. The combination of Kibbe, Xue, and Oczypok does not disclose a self-assembled nanomaterial comprising: a plurality of peptide amphiphiles of claim 1, wherein the targeting moiety localizes to receptor for advanced glycation end products (RAGE) or angiotensin-converting enzyme (ACE). Kibbe does, however, disclose a peptide amphiphile wherein: “the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet forming peptide segment”. (Kibbe, claim 1). Regarding targeting RAGE, The peptide disclosed by Xue targets RAGE.
Regarding the self-assembled nanomaterial, Qiu discloses that “Among these molecular self-assembling materials, a category of amphiphilic peptides characterized by the structure of a hydrophobic tail and a hydrophilic head have received especially rapid development. Taking hydrophobic interaction as the predominant driving force, they could undergo self-assembly in aqueous solution and form various nanostructures with certain applications.” (Qiu, page 5003, para. 2). The disclosed amphiphilic peptide possesses a hydrophobic non-peptide segment and a charged peptide segment. These features are analogous to the hydrophobic tail and a hydrophilic head described by Qiu.
Additionally, So discloses that: “Nanofibers self-assemble from PA molecules comprising a hydrophobic alkyl tail, a β-sheet region involving amino acids with high propensities to form β-sheets, a charged region composed of acidic or basic amino acids, and an epitope for specific biological activity.” (So, page 1, col. 2, para. 1) Note that these are the same elements as recited in Applicant claim 1 from which this claim depends.
Furthermore, MPEP 2112.01(II) recites: “A chemical composition and its properties are inseparable.”. Therefore, an amphiphilic peptide that possesses all the elements recited by Applicant claim 18 would necessarily have the same self-assembling properties. As shown above, all elements are present or obvious.
It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to use the amphiphilic peptide of Kibbe, Xue, and Oczypok to arrive at the self-assembled nanomaterial of Applicant claim 18. This peptide amphiphile would necessarily have the same properties as the claimed peptide amphiphile because they possess the same structural motif and therefore be a self-assembled nanomaterial. A person of ordinary skill in the art would also be motivated to use the structural motif described by Kibbe, Xue, and Oczypok to achieve the self-assembled nanomaterial described by Qui as needing “a hydrophobic tail and a hydrophilic head” and that of So, which recites the same primary elements. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide amphiphile fulfills the requirements described by Qui and So. Consequently, claim 18 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and in further view of Qiu et al. and So et al. and rejected.
Regarding claim 34, claim 18 is obvious as described above. Kibbe recites: “In some embodiments, provided herein are self-assembled nanofibers formed of the peptide amphiphiles
described above (or elsewhere herein).” (Kibbe, para [0008]). MPEP 2112.01(II) recites: “A chemical composition and its properties are inseparable.”. Therefore, a self-assembled nanomaterial that possesses all the elements recited by Applicant claim 18, from which claim 34 depends, would necessarily have the same self-assembling properties and be able to form fibers as described in Kibbe. As shown above, all elements are present or obvious.
It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date to use the self-assembling nanomaterial of Kibbe, Xue, Oczypok, Qiu, and So to create a nanofiber. A person of ordinary skill in the art would have a reasonable expectation of success because the elements disclosed by Kibbe are also described by Kibbe as being able to form nanofibers (Kibbe, para [0008]). Consequently, claim 34 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and in further view of Qiu et al. and So et al. and rejected.
Regarding claim 36, claim 18 is obvious as described above. Applicant claim 36 recites the self-assembled nanomaterial of claim 18, wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment; and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety. Kibbe recites a peptide amphiphile comprising the above-described elements wherein: “the C-terminus of the B-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment; and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety.” (Kibbe, claim 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to add the limitations recited by Applicant claim 34 using the disclosed structure of the peptide amphiphile of Kibbe because the additional limitations of claim 34 are recited by Kibbe claim 1. A person of ordinary skill in the art would have a reasonable expectation of success because they are identical limitations in this case. Consequently, claim 34 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and in further view of Qiu et al. and So et al. and rejected.
Claims 23, 24, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Kibbe et al. (US 2015/0151002, filed 9/30/2014, published 6/4/2015) in view of Xue et al. (Xue et al., Structure, 24:9, 1509 – 1522 (2016)), Oczypok et al. (Oczypok, et al. Paediatric respiratory reviews 23:40-49 (2017), as evidenced by NCBI Accession NP_006263 (deposited 1988, accessed 11/4/2025) as applied to claim 1 above, and, in further view of Qiu et al. (Qiu, et al., International Journal of Nanomedicine, 13, 5003–5022. (2018)) and So et al. (So et al., Adv. Biosys. 2, 1700123 (2018)) as applied to claim 18 above, and further in view of Li et al. (Li et al., International Immunopharmacology,16,2, Pages 248-253, (2013).
Regarding claim 23, claim 18 is obvious as described above. The combination of Kibbe, Xue, Oczypok, Qiu, and So does not disclose a therapeutic agent. However, Li discloses that: “In summary, treatment with GLN attenuated smoke inhalation induced acute and chronic lung injury processes in rats and its protective mechanism seems to be involved in inhibiting inflammatory response and enhancing HSP expression. Accordingly, GLN could be considered as a potential therapeutic agent for preventing lung injury against smoke inhalation.” (Li, page 253, col. 1, para. 2).
It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to combine the self-assembled nanomaterial of Kibbe, Xue, Oczypok, Qiu, and So with a therapeutic meant for action on pulmonary tissue as disclosed by Li. A person of ordinary skill in the art would have a reasonable expectation of success because the self-assembled nanomaterial of Kibbe, Xue, Oczypok, Qiu, and So is targeted to pulmonary tissue and glutamine as shown by Li to help treat several different pulmonary conditions (Li, Abstract). Consequently, claim 23 is obvious over Kibbe in view of over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, further view of Qiu et al. and So et al. as applied to claim 18 above, and in further view of Li et al., and rejected.
Regarding claim 24, claim 23 is obvious as described above. So describes the case wherein peptide amphiphiles encapsulate a therapeutic agent: “Upon addition of this excess base to pH 7.5, 40% ApoA1 PA encapsulated LXR agonist in a 1:1 weight ratio (the encapsulation will be referred to as LXR-40% ApoA1 PA). Encapsulation did not impact the ability of the PA to form nanofibers (Figure 2a).” (So, page 4, col. 1, para. 2). It would have been prima facie obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to use the self-assembled nanomaterial of Kibbe, Xue, Oczypok, Qiu, and So to encapsulate therapeutic agents as described by So. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide amphiphiles of So are described as having all the same elements as Applicant claim 1 (So, page 1, col. 2, para. 1), and So further describes that encapsulation of therapeutics did not impact the ability of peptide amphiphiles to form nanofibers (So, page 4, col. 1, para. 2). Consequently, claim 24 is obvious over Kibbe in view of over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, and in further view of Qiu et al. and So et al. and rejected.in further view of Li et al., and rejected.
Regarding claim 25, claim 23 is obvious as described above. The therapeutic molecule described by Li et al. above is glutamine. Consequently, claim 25 is obvious over Kibbe et al. in view of Xue et al., Oczypok et al., as evidenced by NCBI Accession NP_006263 as applied to claim 1 above, further view of Qiu et al. and So et al. as applied to claim 18 above, and in further view of Li et al., and rejected.
Response to Arguments
Regarding claims 1, 2, and 17, Applicant asserts the following: “First, Applicant respectfully submits that the teachings in paragraph [0048] are a very broad, unspecified teaching in Kibbe that does not provide any actual guidance about how to modify Kibbe's peptide amphiphiles - let alone provide a reason to change Kibbe's peptide amphiphiles to target pulmonary tissue, instead of providing localized delivery to sites of neointimal hyperplasia. It is not enough to recite such a general motivation. The Federal Circuit has held that "to establish obviousness, it is insufficient to allege a general motivation to discover an undefined solution that could take many possible forms," and that "knowledge of a problem and motivation to solve it are entirely different from motivation to combine particular references to reach the particular [claim]." See In re Armodafinil Patent Litigation Inc v. Apotex, 939 F.Suppl.2d 456, 500 (Fed. Cir. 2013) (quoting Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1373-75 (Fed. Cir. 2008).
Furthermore, the references to the teachings of Oczypok and Xue do not change the fact that, again, Kibbe teaches 1. the importance of localized delivery, and 2. the problems stemming from systemic delivery. The mere fact that Kibbe contains one broad sentence mentioning "targeting peptides" does not negate either of these teachings; this is the sort of "general motivation" that the Federal Circuit has already established is insufficient to establish the necessary motivation. ” (Applicant Reply, page 10, para. 1).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Furthermore, MPEP 2123(I) states: “"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).”
As described above, Kibbe not only contemplates the use of targeting moieties such as those disclosed by Xue, but Kibbe disclosed that such targeting is a known modification: “Targeting moieties may direct PA structures (and therefore the therapeutics attached thereto or encapsulated therein) to specific organs, tissues, cell types, Subcellular locations (e.g., organelles), pathogens (e.g., viruses, bacteria, etc.), diseases (e.g., to cancerous cells), etc. Targeting peptides and other moieties for achieving such localization are understood.” (Kibbe et al., para. [0048]).
The fact that Kibbe may discourage systemic therapies is not especially relevant to the analysis of a target therapy and as noted above, Kibbe contemplates the usage of the composition of Kibbe in a targeted therapy.
Applicant also asserts: “Relatedly, a determination of obviousness requires a reasonable expectation of success in modifying a reference to reach the claims at issue. See, e.g., Wyers v. Master Lock Co., 616 F.3d 1231, 1242 (Fed. Cir. 2010). The Office Action asserts on page 12 that "A person of ordinary skill in the art would have a reasonable expectation of success because Xue shows that the sequence AMVTTACHEFFEH (Genbank Accession NP_006263) interacts with the RAGE receptor." As mentioned in the response submitted on August 20, 2025 in connection with the instant application, there is no indication in Kibbe that the drugs with which Kibbe's peptide amphiphiles are functionalized would serve to treat neointimal hyperplasia if they were not targeted to the site of the neointimal hyperplasia (or that a higher dose, if employed to counteract the non-targeted delivery, would avoid the issues from systemic treatment discussed in Kibbe's paragraph [0004].” (Applicant Reply, page 10, para. 3).
Kibbe discloses advantages of drug delivery utilizing the disclosed amphiphile: “Biocompatable nanoscale drug carriers incorporating targeting information have the potential to provide Substantial improvement of drug delivery methods with high efficacy and minimal toxicity. NanoStructures can combine polyvalent display of small molecules (Hrkach, J., et al. Science Translational Medicine, Vol. 4 128ra139-128ra139 (2012).; herein incorporated by reference in its entirety), aptamers (Farokhzad, O.C., et al. Cancer Research, Vol. 647668-7672 (AACR, 2004). ;herein incorporated by reference in its entirety), antibodies (Qian, X., et al. Nat Biotechnol, Vol. 2683-90 (2007).; herein incorporated by reference in its entirety), and proteins (Davis, M. E., et al. Nature, Vol. 464 1067-1070 (2010).: Choi et al. Proceedings of the National
Academy of Sciences, Vol. 107 1235-1240 (2010).; herein incorporated by reference in their entireties) on their surfaces designed to release drugs at a targeted site (Vance et al. Advanced Drug Delivery Reviews, Vol. 61931-939 (2009).: herein incorporated by reference in its entirety).” (Kibbe et al., para. [0003]).
Kibbe also describes targeting said peptide amphiphiles as a known technology: ““Targeting moieties may direct PA structures (and therefore the therapeutics attached thereto or encapsulated therein) to specific organs, tissues, cell types, Subcellular locations (e.g., organelles), pathogens (e.g., viruses, bacteria, etc.), diseases (e.g., to cancerous cells), etc. Targeting peptides and other moieties for achieving such localization are understood.” (Kibbe et al., para. [0048]). (Emphasis added).
Therefore, a person of ordinary skill in the art would have a reasonable expectation of success of using a targeting peptide such as the one disclosed by Xue to target the peptide amphiphile of Kibbe because Kibbe discloses exactly such a scenario as described above.
The rejection of claims 1, 2, and 17 is maintained.
Regarding claim 3, claim 2 is obvious as described above. Marshall and Fauchere are relied upon for residue properties, not to cure purported deficiencies in the rejection of claim 2. Furthermore, the peptide of Xue has the sequence AMVTTACHEFFEH, which is identical to Applicant SEQ ID NO: 2.
The rejection of claim 3 is maintained.
Regarding claim 4, claim 1 is obvious as described above. Vasileiadis is relied upon for teachings regarding ACE as a target, not to cure purported deficiencies in the rejection of claim 1.
The rejection of claim 4 is maintained.
Regarding claim 5, claim 4 is obvious as described above. Guo is relied upon for teachings regarding ACE targeting peptides, not to cure purported deficiencies in the rejection of claim 4.
The rejection of claim 5 is maintained.
Regarding claims 6 and 8, claim 1 is obvious as described above. Li is relied upon for teachings regarding glutamine therapy for smoke inhalation, not to cure purported deficiencies in the rejection of claim 1.
The rejection of claims 6 and 8 are maintained.
Regarding claim 7, claim 6 is obvious as described above. He is relied upon for teachings regarding covalently bound therapeutics, not to cure purported deficiencies in the rejection of claim 6.
The rejection of claim 7 is maintained.
Regarding claims 18, 34, and 36, claim 1 is obvious as described above. Qiu and So are relied upon for teachings regarding self-assembling nanostructures, not to cure purported deficiencies in the rejection of claim 1.
The rejection of claims 18, 34, and 36 are maintained.
Regarding claims 23, 24, and 25, claim 18 is obvious as described above. Li is relied upon for teachings regarding glutamine therapy for smoke inhalation, not to cure purported deficiencies in the rejection of claim 18.
The rejection of claims 23, 24, and 25 are maintained.
Conclusion
No claim is allowed.
Claims 1-8, 17, 18, 23-25, 34, and 36 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DAVID PAUL BOWLES/Examiner, Art Unit 1654
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
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