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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 1/26/2023 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.
Claim Status
Claims 65-84, filed 1/26/2023, are pending. Claims 65-84 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 68-70 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.
Regarding claim 68, claim 68 recites the limitation "the cell adhesion receptor" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 69, claim 69 fails to resolve the indefiniteness of claim 68 and therefore is also rejected.
Regarding claim 70, claim 70 fails to resolve the indefiniteness of claim 68 and therefore is also rejected.
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.
Claims 65-72, 75, 77-80 are rejected under 35 U.S.C. 103 as being unpatentable in view of Cochran et al. (Cochran et al. US20140073518, published 3/13/2014 (2014)) in view of Banik et al. (Banik, et al. https://chemrxiv.org/engage/chemrxiv/article-details/60c745e6337d6ca40ee27078, posted Mar 2019 (2019)) and Rathinam et al. (Rathinam, et al. Cancer and Metastasis Reviews 29.1: 223-237 (2010)) as evidenced by Barczyk et al. (Barczyk, et al. Cell and tissue research 339.1: 269-280 (2010)).
Regarding claim 65, claim 65 recites: “A bifunctional molecule comprising:
a first moiety that specifically binds a cell surface molecule or extracellular molecule, wherein the first moiety is a knottin peptide comprising an engineered loop that binds to the cell surface molecule; and
a second moiety that specifically binds a lysosomal targeting molecule.”
Cochran discloses “a knottin polypeptide having therein a knottin scaffold comprising therein a binding loop having a non-native sequence for binding to a first target; ..” as part of a fusion protein. (Cochran, claim 1). Furthermore, these knottin polypeptides may be engineered to bind to one or more of (a) alpha v beta 3 integrin, (b) alpha v beta 5 integrin, and (c) alpha 5 beta 1 integrin (Cochran, claim 12). Integrins are known to be cell surface molecules as evidenced by Baczyk (Barczyk, page 272, Fig. 3). Lastly, Cochran discloses that the non-native sequence binding loop is an engineered loop: “The spacing between Cys residues is important in the present invention, as is the molecular topology and conformation of the engineered loop. The engineered loop may contain RGD to provide an integrin binding loop.” (Cochran, para. [0068]).
Cochran discloses that the knottin peptide may be in a fusion product with a receptor tyrosine kinase Ig1 domain: “ In certain aspects of the invention, the second polypeptide is a receptor tyrosine kinase Ig1 domain.” (Cochran, para. [0015]). However, Cochran does not disclose a second moiety that specifically binds a lysosomal targeting molecule.
However, Banik discloses a conjugate that are “capable of binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein” (Banik et al., page 1, para. 1). The purpose of this conjugate is to target therapeutic targets for destruction by the lysosome: “Therefore a general strategy for targeting secreted and plasma membrane proteins for degradation remains an unmet need that could dramatically impact human health.” (Banik et al., page 1, para. 2).
Banik discloses that a lysosome targeting receptor of interest is cation-independent mannose-6-phosphate receptor (CI-M6PR) (Banik et al. page 1, para. 4). Banik also discloses that this receptor endogenously transports proteins bearing N-glycans capped with mannose-6-phosphate (M6P) residues to lysosomes (Banik et al., page 1, para. 4). Banik discloses that this motif can be used to create a lysosome targeting chimera (LYTAC) platform (Banik et al., page 2, para. 1). Lastly, this strategy was shown to be effective at trafficking membrane-associated proteins of interested to the lysosome: “We next asked if LYTACs could be used to accelerate the degradation of membrane-associated extracellular proteins” (Banik et al., page 3, para. 4) and “EGFR degradation was also observed in breast cancer (BT474, MDA-MB-361) and lung cancer (A549 cell lines (Fig. S14) (Banik et al., page 4, para. 1).
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 integrin-targeting knotting peptide of Cochran with the lysosome targeting receptor agonist (proteins bearing N-glycans capped with mannose-6-phosphate (M6P)) of Banik to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to make such a combination because overexpression of integrins is known to be involved with many cancer types, such as breast cancer as described by Rathinam: “ In MDA-MB-231 human breast cancer cells, a critical sequence of an RNA aptamer, termed OPN-R3, ablates cell surface binding of OPN to αvβ3 integrin receptors to reduce metastases [60]. Overexpression of both OPN and pSTAT3 enhances breast tumor progression, so they might be important targets for a therapeutic approach to reduce breast cancer progression.”(Rathinam, page 227, col. 2, para. 2).
A person of ordinary skill in the art would have had a reasonable expectation of success for this fusion product because Banik et al. describes how this lysosomal trafficking approach works for several membrane-associated proteins. The results for EGFR are described above. CD71 was successfully degraded: “Upon incubation of Jurkat cells with a mouse-anti-CD71 antibody and AB-1, signification degradation of CD71 was observed (>80%, Fig. 4I)” (Banik, et al., page 4, para. 3) PD-L1 was also successfully degraded: “After 36 hours, 50% downregulation of PD-L1 was observed” (Banik et al., pages 5, para. 1).
Consequently, claim 65 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 66, claim 65 is obvious as described above. Claim 66 further recites the case wherein the knottin peptide is selected from the group consisting of: an EETI-II peptide, an AgRP peptide, a w-conotoxin peptide, a Kalata B1 peptide, an MCoTI-II peptide, an agatoxin peptide, and a chlorotoxin peptide. Cochran discloses a knottin polypeptide wherein: “The fusion protein of claim 9 wherein the knottin polypeptide is selected from the group consisting of EETI-II, AgRP, and agatoxin.” (Cochran et al., claim 11). Consequently, claim 66 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 67, claim 65 is obvious as described above. Claim 67 further recites the case wherein the cell surface molecule is a cell surface receptor. As discussed above, the knottin peptide binds to integrin molecules. Barczyk evidences that integrins are cell surface receptors (Barczyk et al., page 272, Fig. 2). Consequently, claim 67 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 68, claim 67 is obvious as described above. Claim 68 further recites the case wherein the cell adhesion receptor is an integrin. As discussed above, the knottin peptide binds to integrin molecules. Consequently, claim 68 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 69, claim 68 is obvious as described above. Claim 69 further recites wherein the integrin is selected from the group consisting of: αvβ3 intregin, αvβ5 intregin, αvβ6 intregin, α5β1 intregin, and any combination thereof. Cochran discloses a knottin polypeptide that: “contains a sequence that mediates binding to one or more of (a) alpha v beta 3 integrin, (b) alpha v beta 5 integrin, and (c) alpha 5 beta 1 integrin.” (Cochran et al., claim 6). Consequently, claim 69 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al. and rejected.
Regarding claim 70, claim 68 is obvious as described above. Claim 70 further recites the case wherein the knottin peptide is an integrin- binding knottin peptide comprising an amino acid sequence having 80% or greater identity to the amino acid sequence set forth in SEQ ID NO:7 or SEQ ID NO:8. Cochran discloses SEQ ID NO: 32 which is identical to Applicant SEQ ID NO: 7: GCPQGRGDWAPTSCKQDSDCRAGCVCGPNGFCG (Cochran et al., para. [0085]). Cochran also discloses SEQ ID NO: 26, which reads on Applicant SEQ ID NO: 8: GCPRPRGDNPPLTCKQDSDCLAGCVCGPNGFCG, in the case where Xaa is Phe (Cochran et al., para. [0085]). Consequently, claim 70 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 71, claim 65 is obvious as described above. Claim 71 further recites the case wherein the cell surface molecule is present on a cancer cell. Cochran discloses that: “
The αvβ3 integrin receptor is over-expressed on many solid tumor cells making it an important cancer target.” (Cochran, para. [0102]). Consequently, claim 71 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 72, claim 65 is obvious as described above. Claim 72 further recites the case wherein the lysosomal targeting molecule is a mannose-6-phosphate receptor (M6PR) or an asialoglycoprotein receptor (ASGPR). Banik discloses that a lysosome targeting receptor of interest is cation-independent mannose-6-phosphate receptor (CI-M6PR) (Banik et al. page 1, para. 4). Consequently, claim 72 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 75, claim 65 is obvious as described above. Claim 75 further recites a method: “An in vitro or in vivo method of degrading a cell surface molecule, comprising: contacting the cell surface molecule with the bifunctional molecule of claim 65 under conditions in which the lysosomal targeting molecule shuttles the cell surface molecule to the lysosome for degradation.”
Banik discloses that the method of contacting a cell surface molecule with a bifunctional molecule features a target binding motif and a poly(M6Pn) motif successfully traffics the target to the lysosome: : “We next asked if LYTACs could be used to accelerate the degradation of membrane-associated extracellular proteins” (Banik et al., page 3, para. 4) and “EGFR degradation was also observed in breast cancer (BT474, MDA-MB-361) and lung cancer (A549 cell lines (Fig. S14) (Banik et al., page 4, para. 1).
Consequently, claim 75 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected
Regarding claim 77, claim 65 is obvious as described above. Claim 77 further recites a pharmaceutical composition comprising: the bifunctional molecule of claim 65; and a pharmaceutically acceptable carrier. Cochran discloses the usage of pharmaceutical compositions: “The present fusion proteins may be administered in vitro, such as in cell culture studies, or to cells intended for transplant, but may also be administered in vivo. A variety of formulations and dosing regiments used for therapeutic proteins may be employed. The pharmaceutical compositions may contain, in addition to the CFP, suitable pharmaceutically acceptable carriers, biologically compatible vehicles and additives which are suitable for administration to an animal (for example, physiological saline) and eventually comprising auxiliaries (like excipients, stabilizers or diluents) which facilitate the processing of the active fusion proteins into preparations which can be used pharmaceutically.” (Cochran, para. [0111]). Consequently, claim 77 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 78, claim 77 is obvious as described above. Claim 78 further discloses the case wherein the pharmaceutical composition is formulated for parenteral administration. Cochran discloses parenteral administration: “Any accepted mode of administration can be used and determined by those skilled in the art to establish the desired blood levels of then fusion protein. For example, administration may be by various parenteral routes such as subcutaneous, intravenous, epidural, topical, intradermal, intrathecal, direct intraventricular, intraperitoneal, transdermal (e.g. in slow release formulations), intramuscular, intraperitoneal, intranasal, intrapulmonary (inhaled), intraocular, oral, or buccal routes.” (Cochran et al., para. [0113]). Consequently, claim 78 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 79, claim 77 is obvious as described above. Claim 79 further discloses a method comprising administering to an individual in need thereof the pharmaceutical composition of claim 77. Cochran discloses that: “The αvβ3 integrin receptor is over-expressed on many solid tumor cells making it an important cancer target.” (Cochran, para. [0102]). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the composition of claim 77 to a person with a solid tumor overexpressing an integrin receptor for the purposes of downregulating the receptor. A person of ordinary skill in the art would have a reasonable expectation of success because of the results described in Banik regarding the results with respect to membrane-associated proteins (Banik et al., page 3, para. 4). Consequently, claim 79 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 80, claim 77 is obvious as described above. Claim 80 further discloses a method of treating cancer comprising administering to an individual having cancer an effective amount of the pharmaceutical composition of claim 77. Cochran discloses that: “The αvβ3 integrin receptor is over-expressed on many solid tumor cells making it an important cancer target.” (Cochran, para. [0102]). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the composition of claim 77 to a person with a solid tumor overexpressing an integrin receptor for the purposes of downregulating the receptor. A person of ordinary skill in the art would have a reasonable expectation of success because of the results described in Banik regarding the results with respect to membrane-associated proteins (Banik et al., page 3, para. 4). Consequently, claim 80 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Claims 73, 74, 76 are rejected under 35 U.S.C. 103 as being unpatentable in view of Cochran et al. (Cochran et al. US20140073518, published 3/13/2014 (2014)) in view of Banik et al. (Banik, et al. https://chemrxiv.org/engage/chemrxiv/article-details/60c745e6337d6ca40ee27078, posted Mar 2019 (2019)) and Rathinam et al. (Rathinam, et al. Cancer and Metastasis Reviews 29.1: 223-237 (2010)) as evidenced by Barczyk et al. (Barczyk, et al. Cell and tissue research 339.1: 269-280 (2010)).
Regarding claim 73, claim 73 recites a bifunctional molecule comprising: a first moiety that specifically binds an integrin; and a second moiety that specifically binds a lysosomal targeting molecule.
Cochran discloses “a knottin polypeptide having therein a knottin scaffold comprising therein a binding loop having a non-native sequence for binding to a first target; ..” as part of a fusion protein. (Cochran, claim 1). Furthermore, these knottin polypeptides may be engineered to bind to one or more of (a) alpha v beta 3 integrin, (b) alpha v beta 5 integrin, and (c) alpha 5 beta 1 integrin (Cochran, claim 12). Integrins are known to be cell surface molecules as evidenced by Baczyk (Barczyk, page 272, Fig. 3). Lastly, Cochran discloses that the non-native sequence binding loop is an engineered loop: “The spacing between Cys residues is important in the present invention, as is the molecular topology and conformation of the engineered loop. The engineered loop may contain RGD to provide an integrin binding loop.” (Cochran, para. [0068]).
Cochran discloses that the knottin peptide may be in a fusion product with a receptor tyrosine kinase Ig1 domain: “ In certain aspects of the invention, the second polypeptide is a receptor tyrosine kinase Ig1 domain.” (Cochran, para. [0015]). However, Cochran does not disclose a second moiety that specifically binds a lysosomal targeting molecule.
However, Banik discloses a conjugate that are “capable of binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein” (Banik et al., page 1, para. 1). The purpose of this conjugate is to target therapeutic targets for destruction by the lysosome: “Therefore a general strategy for targeting secreted and plasma membrane proteins for degradation remains an unmet need that could dramatically impact human health.” (Banik et al., page 1, para. 2).
Banik discloses that a lysosome targeting receptor of interest is cation-independent mannose-6-phosphate receptor (CI-M6PR) (Banik et al. page 1, para. 4). Banik also discloses that this receptor endogenously transports proteins bearing N-glycans capped with mannose-6-phosphate (M6P) residues to lysosomes (Banik et al., page 1, para. 4). Banik discloses that this motif can be used to create a lysosome targeting chimera (LYTAC) platform (Banik et al., page 2, para. 1). Lastly, this strategy was shown to be effective at trafficking membrane-associated proteins of interested to the lysosome: “We next asked if LYTACs could be used to accelerate the degradation of membrane-associated extracellular proteins” (Banik et al., page 3, para. 4) and “EGFR degradation was also observed in breast cancer (BT474, MDA-MB-361) and lung cancer (A549 cell lines (Fig. S14) (Banik et al., page 4, para. 1).
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 integrin-targeting knotting peptide of Cochran with the lysosome targeting receptor agonist (proteins bearing N-glycans capped with mannose-6-phosphate (M6P)) of Banik to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to make such a combination because overexpression of integrins is known to be involved with many cancer types, such as breast cancer as described by Rathinam: “ In MDA-MB-231 human breast cancer cells, a critical sequence of an RNA aptamer, termed OPN-R3, ablates cell surface binding of OPN to αvβ3 integrin receptors to reduce metastases [60]. Overexpression of both OPN and pSTAT3 enhances breast tumor progression, so they might be important targets for a therapeutic approach to reduce breast cancer progression.”(Rathinam, page 227, col. 2, para. 2).
A person of ordinary skill in the art would have had a reasonable expectation of success for this fusion product because Banik et al. describes how this lysosomal trafficking approach works for several membrane-associated proteins. The results for EGFR are described above. CD71 was successfully degraded: “Upon incubation of Jurkat cells with a mouse-anti-CD71 antibody and AB-1, signification degradation of CD71 was observed (>80%, Fig. 4I)” (Banik, et al., page 4, para. 3) PD-L1 was also successfully degraded: “After 36 hours, 50% downregulation of PD-L1 was observed” (Banik et al., pages 5, para. 1).
Consequently, claim 73 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 74, claim 73 is obvious as described above. Claim 74 further recites wherein the integrin is selected from the group consisting of: αvβ1 intregin, αvβ3 intregin, αvβ5 intregin, αvβ6 intregin, α5β1 intregin, and any combination thereof. Cochran discloses a knottin polypeptide that: “contains a sequence that mediates binding to one or more of (a) alpha v beta 3 integrin, (b) alpha v beta 5 integrin, and (c) alpha 5 beta 1 integrin.” (Cochran et al., claim 6). Consequently, claim 74 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al. and rejected.
Regarding claim 76, claim 73 is obvious as described above. Claim 76 further recites: “An in vitro or in vivo method of degrading an integrin, comprising: contacting the integrin with the bifunctional molecule of claim 73 under conditions in which the lysosomal targeting molecule shuttles the integrin to the lysosome for degradation.”
Banik discloses that the method of contacting a cell surface molecule with a bifunctional molecule features a target binding motif and a poly(M6Pn) motif successfully traffics the target to the lysosome: : “We next asked if LYTACs could be used to accelerate the degradation of membrane-associated extracellular proteins” (Banik et al., page 3, para. 4) and “EGFR degradation was also observed in breast cancer (BT474, MDA-MB-361) and lung cancer (A549 cell lines (Fig. S14) (Banik et al., page 4, para. 1). A person of ordinary skill in the art would have a reasonable expectation that a LYTAC system using a poly (M6Pn) and a targeting motif for integrins would produce at least some level of accelerated degradation based on the results Banik. Consequently, claim 75 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected
Regarding claim 81, claim 73 is obvious as described above. Claim 81 further recites a pharmaceutical composition comprising: the bifunctional molecule of claim 73; and a pharmaceutically acceptable carrier. Cochran discloses the usage of pharmaceutical compositions: “The present fusion proteins may be administered in vitro, such as in cell culture studies, or to cells intended for transplant, but may also be administered in vivo. A variety of formulations and dosing regiments used for therapeutic proteins may be employed. The pharmaceutical compositions may contain, in addition to the CFP, suitable pharmaceutically acceptable carriers, biologically compatible vehicles and additives which are suitable for administration to an animal (for example, physiological saline) and eventually comprising auxiliaries (like excipients, stabilizers or diluents) which facilitate the processing of the active fusion proteins into preparations which can be used pharmaceutically.” (Cochran, para. [0111]). Consequently, claim 81 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 82, claim 81 is obvious as described above. Claim 82 further discloses the case wherein the pharmaceutical composition is formulated for parenteral administration. Cochran discloses parenteral administration: “Any accepted mode of administration can be used and determined by those skilled in the art to establish the desired blood levels of then fusion protein. For example, administration may be by various parenteral routes such as subcutaneous, intravenous, epidural, topical, intradermal, intrathecal, direct intraventricular, intraperitoneal, transdermal (e.g. in slow release formulations), intramuscular, intraperitoneal, intranasal, intrapulmonary (inhaled), intraocular, oral, or buccal routes.” (Cochran et al., para. [0113]). Consequently, claim 82 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 83, claim 81 is obvious as described above. Claim 83 further discloses a method comprising administering to an individual in need thereof the pharmaceutical composition of claim 81. Cochran discloses that: “The αvβ3 integrin receptor is over-expressed on many solid tumor cells making it an important cancer target.” (Cochran, para. [0102]). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the composition of claim 81 to a person with a solid tumor overexpressing an integrin receptor for the purposes of downregulating the receptor. A person of ordinary skill in the art would have a reasonable expectation of success because of the results described in Banik regarding the results with respect to membrane-associated proteins (Banik et al., page 3, para. 4). Consequently, claim 83 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Regarding claim 84, claim 81 is obvious as described above. Claim 84 further discloses a method of treating cancer comprising administering to an individual having cancer an effective amount of the pharmaceutical composition of claim 81. Cochran discloses that: “The αvβ3 integrin receptor is over-expressed on many solid tumor cells making it an important cancer target.” (Cochran, para. [0102]). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the composition of claim 77 to a person with a solid tumor overexpressing an integrin receptor for the purposes of downregulating the receptor. A person of ordinary skill in the art would have a reasonable expectation of success because of the results described in Banik regarding the results with respect to membrane-associated proteins (Banik et al., page 3, para. 4). Consequently, claim 84 is obvious over Cochran et al. in view of Banik et al. and Rathinam et al. as evidenced by Barczyk et al and rejected.
Conclusion
No claim is allowed.
Claims 65-84 are rejected.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654