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 .
Status of Claims
Claims 1-3, 14-18, 22-23 and 30-37 are pending following the Reply filed 01/02/2026. Claims 4-13 have been cancelled. Claims 1-3, 14-18 and 22-23 have been amended without introducing new matter. Claims 30-37 have been newly added without introducing new matter. Claims 1-3, 14-18, 22-23 and 30-37 have been examined on the merits.
Withdrawn
Any objection or rejection of claims 4-13 is moot because the claims are cancelled.
The objection to the specification is withdrawn in light of the amended specification filed 01/02/2026.
The objections of claim 14-15 are withdrawn in light of the amendments.
The scope of enablement rejection of claim 23 under 35 U.S.C. 112(a) is withdrawn in light of the amendments. The claim, as amended, is directed to a method of treating cancer, which is enabled by Applicant’s disclosure as previously discussed in the rejection.
The rejections under 35 U.S.C. 102 are withdrawn in light of the amendments. See Response to Arguments for further discussion.
Maintained Rejections and New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 14 and 37 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.
Claims 14 and 37 recite the limitation "the second protein" in line 1. There is insufficient antecedent basis for this limitation in the claim. Each claim depends from claim 1 which does not recite “a second protein”.
In the interest of compact prosecution, claim 14 is given its broadest reasonable interpretation, “wherein the conjugate comprises a second protein that is…” one of the listed proteins. Claim 37 is given its broadest reasonable interpretation, “wherein the conjugate comprises a second protein that is BRD.”
Claim Rejections - 35 USC § 103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claim(s) 1-3, 14, 18, 22, 30, 35 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herce (US 20230330238 A1; effectively filed 10/14/2020; previously cited) and further in view of Xu (U.S. 9,765,022 B2; previously cited).
Regarding claim 1, Herce teaches chimeric conjugates, i.e., proteolysis targeting chimeras (PROTACs) that target the degradation of host proteins involved in viral pathogenesis (see pg. 1, para. [0003]), wherein the chimera comprises a first moiety attached to a second moiety (see pg. 1, para. [0009]). Herce teaches the moieties may be peptides (see pg. 1, para. [0006]) and are “conjugated” to one another by a direct or indirect covalent or non-covalent interaction (see pg. 28, para. [0257]). Herce teaches the first moiety binds to a first protein targeted for degradation, and the second moiety binds to a second protein, wherein the second protein is a “protein degrader” (see pgs. 1-2, para. [0009]). Thus, Herce teaches a conjugate, comprising a PROTAC, and a first protein bound to a first moiety, wherein the PROTAC and the first moiety are covalently or non-covalently bonded to each other.
Examiner notes that as used herein, the “second protein” of Herce’s disclosure is equivalent to the “first protein” of the present claims (“the protein degrader”), and the “first protein” of Herce’s disclosure is equivalent to the “second protein” of the present claims (“the target protein”).
Herce teaches the second protein (“protein degrader”) may be a Von Hippel-Lindau (VHL) ligase (see pg. 2, para. [0020]).
Herce does not teach a membrane encapsulating the conjugate.
Xu teaches that to achieve a therapeutic effect, a drug must be delivered to its target site, but it is a challenge to deliver a drug that is susceptible to enzymatic degradation or cannot cross cell membranes to reach an intracellular target (see col. 1, lines 15-18). Xu teaches that conventional delivery methods include the use of target-specific delivery vehicles, such as liposomes, polymers, and inorganic nanoparticles (see col. 1, lines 19-22). However, these vehicles are often toxic or inefficient, and there is a need to develop an efficient and safe vehicle for delivering a drug to its target site (see col. 1, lines 24-25, 28-29).
Xu teaches that certain lipid-like compounds are efficient and safe vehicles for use in the delivery of pharmaceutical agents (see col. 1, lines 33-35), wherein the pharmaceutical agent is a small molecule, protein or a peptide, and the compound binds to the pharmaceutical agent to form a nanocomplex (see col. 5, lines 37-41). Xu teaches that the lipid-like compounds facilitate delivery of pharmaceutical agents by forming complexes, e.g., nanocomplexes, wherein the hydrophilic head of such a lipid-like compound binds to a moiety of a pharmaceutical agent that is oppositely charged while its hydrophobic moiety binds to a hydrophobic moiety of the pharmaceutical agent (see col. 16, lines 7-14). Xu teaches that such complexes can be prepared using procedures described in the art, generally by incubating a lipid-like compound and a pharmaceutical agent in a buffer, such as a sodium acetate buffer or phosphate buffered saline (PBS) (see col. 16, lines 15-20). In Xu’s Examples, the lipid-like compounds were prepared and evaluated for delivering a protein (i.e., saporin) into cell lines, and unexpectedly, disulfide lipid-like compound 80-O14B demonstrated much greater saporin delivery efficiency under all four studied conditions than its non-disulfide counterparts (see col. 24, lines 20-24).
Regarding the limitation, “a membrane encapsulating the conjugate”, in view of Applicant’s Examples disclosed in the instant specification, the same 80-O14B lipid nanoparticle was synthesized “according to known literature methods” (see pg. 18, lines 23-24) and was incubated with ARV-771 (PROTAC) and VHL protein in a sodium acetate solution for encapsulation (see pg. 19, lines 2-8). Thus, the membrane-encapsulated “nanoparticle” of the present disclosure uses the same lipid-like compound Xu teaches to form a “nanocomplex” and both are produced by the same process.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). In the instant case, the formation of a membrane by the lipid-like compound of 80-O14B is an inherent property that would necessarily be present when producing the nanoparticle of claim 1, which is prepared by the same process disclosed by Xu. Because the limitations of the claimed product are necessarily present in the prior art combination, the characteristic of the conjugate being “encapsulated” as asserted in the claim is inherently met by the combination of references. See MPEP 2112.
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Herce and Xu, because both references teach the delivery of therapeutic proteins for delivery into host cells. One would have recognized from Xu the advantages of using lipid-like compounds to deliver such therapeutics which can be a safe and efficient means to deliver PROTACs to intracellular host proteins targeted for degradation. As such, one would have been motivated to apply the combination, and it would have been within the ordinary skill in the art to apply the methods taught by Xu (i.e., incubation in a buffered solution) to the PROTACs taught by Herce to form the nanoparticles of the claim. There would have been a reasonable expectation of success, because Xu teaches that such nanocomplexes can be effective at delivering a wide range of molecules, including proteins, to host cells. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 2, Herce teaches that in certain embodiments the association between the conjugated entities is covalent (see pg. 28, para. [0257]).
Regarding claim 3, Herce teaches that in certain embodiments the association between the conjugated entities is non-covalent (see pg. 28, para. [0257]).
Regarding claim 14, Herce teaches the first protein is a bromodomain and extraterminal domain (BET) protein (see pg. 1, para. [0009]).
Regarding claim 18, Xu teaches the lipid-like compound comprising 80-O14B, as discussed above.
Regarding claim 22, Herce teaches a pharmaceutical composition comprising the chimeric conjugate and a pharmaceutically acceptable carrier (see pg. 4, para. [0032]).
Regarding claim 30, Herce teaches the “protein degrader” is a Von Hippel-Lindau (VHL) ligase, as discussed above.
Regarding claim 35, Herce teaches the “protein degrader” may be Cereblon (CRBN) (see pg. 2, para. [0020]).
Regarding claim 37, Herce teaches the first protein (“target protein”) is a bromodomain and extraterminal domain (BET) protein (see pg. 1, para. [0009]), and the BET protein may be a bromodomain (BRD) protein (see pg. 2, para. [0017]).
Claim(s) 1-2, 23 and 32-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ying (WO 2020206608 A1; published 10/15/2020; cited in the IDS filed 04/24/2023) and further in view of Xu.
Regarding claim 1, Ying teaches a protein degradation chimera comprising a first moiety capable of binding to a chaperone complex component, a second moiety that is capable of binding to a target protein, and a tether configured to covalently couple the first and second moieties, wherein the target protein is targeted for degradation (see Abstract). Hence, Ying teaches a first protein (chaperone complex component) bound to a proteolysis-targeting chimera (a protein degradation chimera), i.e., PROTAC, to form a conjugate, wherein the moiety bound to the first protein is covalently coupled to the proteolysis-targeting the chimera.
Ying teaches the chaperone complex component is HSP70 (heat shock protein 70) (see pg. 1, lines 35-39) which plays a key role in the triage of damaged and aberrant proteins for degradation via the ubiquitin-proteasome pathway (see pg. 9, lines 25-30). Hence, Ying teaches the first protein is a heat shock protein.
Ying does not teach a membrane encapsulating the conjugate.
Xu teaches that to achieve a therapeutic effect, a drug must be delivered to its target site, but it is a challenge to deliver a drug that is susceptible to enzymatic degradation or cannot cross cell membranes to reach an intracellular target (see col. 1, lines 15-18). Xu teaches that conventional delivery methods include the use of target-specific delivery vehicles, such as liposomes, polymers, and inorganic nanoparticles (see col. 1, lines 19-22). However, these vehicles are often toxic or inefficient, and there is a need to develop an efficient and safe vehicle for delivering a drug to its target site (see col. 1, lines 24-25, 28-29).
Xu teaches that certain lipid-like compounds are efficient and safe vehicles for use in the delivery of pharmaceutical agents (see col. 1, lines 33-35), wherein the pharmaceutical agent is a small molecule, protein or a peptide, and the compound binds to the pharmaceutical agent to form a nanocomplex (see col. 5, lines 37-41). Xu teaches that the lipid-like compounds facilitate delivery of pharmaceutical agents by forming complexes, e.g., nanocomplexes, wherein the hydrophilic head of such a lipid-like compound binds to a moiety of a pharmaceutical agent that is oppositely charged while its hydrophobic moiety binds to a hydrophobic moiety of the pharmaceutical agent (see col. 16, lines 7-14). Xu teaches that such complexes can be prepared using procedures described in the art, generally by incubating a lipid-like compound and a pharmaceutical agent in a buffer, such as a sodium acetate buffer or phosphate buffered saline (PBS) (see col. 16, lines 15-20). In Xu’s Examples, the lipid-like compounds were prepared and evaluated for delivering a protein (i.e., saporin) into cell lines, and unexpectedly, disulfide lipid-like compound 80-O14B demonstrated much greater saporin delivery efficiency under all four studied conditions than its non-disulfide counterparts (see col. 24, lines 20-24).
Regarding the limitation, “a membrane encapsulating the conjugate”, in view of Applicant’s Examples disclosed in the instant specification, the same 80-O14B lipid nanoparticle was synthesized “according to known literature methods” (see pg. 18, lines 23-24) and was incubated with ARV-771 (PROTAC) and VHL protein in a sodium acetate solution for encapsulation (see pg. 19, lines 2-8). Thus, the lipid-like compound of Xu is equivalent to the “nanoparticle” of the present disclosure, and the nanocomplex is formed using the same methods. Thus, the membrane-encapsulated “nanoparticle” of the present disclosure uses the same lipid-like compound Xu teaches to form a “nanocomplex” and both are produced by the same process.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). In the instant case, the formation of a membrane by the lipid-like compound of 80-O14B is an inherent property that would necessarily be present when producing the nanoparticle of claim 1, which is prepared by the same process disclosed by Xu. Because the limitations of the claimed product are necessarily present in the prior art combination, the characteristic of the conjugate being “encapsulated” as asserted in the claim is inherently met by the combination of references. See MPEP 2112.
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Ying and Xu, because both references teach the delivery of therapeutic proteins for delivery into host cells. One would have recognized from Xu the advantages of using lipid-like compounds to deliver such therapeutics which can be a safe and efficient means to deliver PROTACs to intracellular host proteins targeted for degradation. As such, one would have been motivated to apply the combination, and it would have been within the ordinary skill in the art to apply the methods taught by Xu (i.e., incubation in a buffered solution) to the PROTACs taught by Herce to form the nanoparticles of the claim. There would have been a reasonable expectation of success, because Xu teaches that such nanocomplexes can be effective at delivering a wide range of molecules, including proteins, to host cells. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 2, Ying teaches the first and second moieties are covalently coupled by a tether, as discussed above.
Regarding claim 23, Ying teaches a method for treating cancer, comprising administering a therapeutically effective amount of the protein degradation chimera to a patient in need thereof (see pg. 2, lines 14-16).
Regarding claim 32, Ying teaches the first protein is a heat shock protein, as discussed above.
Regarding claim 33, Ying teaches the heat shock protein is Hsp70, as discussed above.
Claim(s) 15, 17 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ying and Xu, as applied to claims 1-2 and 23 above, and further in view of Gustafson (previously cited).
Regarding claim 15, Ying teaches a first protein (chaperone complex component) which binds to a proteolysis-targeting chimera (a protein degradation chimera), i.e., PROTAC, to form a conjugate, wherein the moiety bound to the first protein is covalently coupled to the proteolysis-targeting chimera, as discussed above. Ying also teaches that many disadvantages are associated with conventional PROTAC molecules, such as resistance developed through E3 ligase mutation, and a need exists for improved/alternative methods and compositions for targeted protein degradation (see pg. 1, lines 20-22). Ying teaches embodiments wherein the chaperone complex component is HSP70 (see pg. 1, line 36). Ying teaches that Hsp90/Hsp70-based chaperone machinery plays a key role in the triage of damaged and aberrant proteins for degradation via the ubiquitin-proteasome pathway (see pg. 9, lines 25-30), and a number of E3 ligases, such as CHIP, have been shown to be closely associated with Hsp90 and Hsp70 (see pg. 9, lines 35-37). Ying teaches that the tumor-targeted protein degradation chimeras (T-PEACH) molecules of the disclosure demonstrate unique properties in being retained in tumors due to their binding affinity to the highly expressed chaperone complex of Hsp 90/70 (see pg. 2, lines 34-39).
Ying does not teach wherein the PROTAC is ARV-110, ARV-471, ARV-766, ARV-771, ARV-825, AR-LDD, DT2216, KT-474, KT-413, KT-333, NX-2127, NX-5948, CG001419, CFT8634, FHD-609, or SARD279.
Gustafson discloses that Androgen Receptor (AR)-dependent transcription is a major driver of prostate tumor cell proliferation (see Abstract) and teaches the development of several approaches for post-translational targeting of specific proteins to the ubiquitin-proteasome system (UPS) (see pg. 2, para. 1). Gustafson teaches the coupling of a hydrophobic tag to an androgen receptor agonist converts it to a potent Selective Androgen Receptor Degrader (SARD) capable of inducing >50% of AR degradation (DC50) at 1 µM, while retaining anti-proliferative activity in cell lines resistant to current standard-of-care drugs for castration-resistant prostate cancer (CRPC) (see pg. 2, para. 1 to pg. 3, para. 1). To induce AR degradation via a hydrophobic tagging approach, Gustafson designed a series of selective androgen receptor degraders (SARDs) (see pg. 3, para. 3) and investigated the possible involvement of Heat Shock Proteins (HSPs), given their known role in stabilizing misfolded proteins or targeting them for degradation by the UPS (see pg. 4, para. 1). Gustafson teaches that Hsp70 and the associated E3 ubiquitin ligase CHIP play a key role in targeting intractably misfolded proteins to the UPS, and hydrophobic tags lead to enhanced association with Hsp70 (see pg. 4, para. 1). Gustafson discloses that linking a hydrophobic tag-based degron to an AR agonist creates a novel class of anti-androgens (SARDs) that induce targeted AR degradation and override some resistance mechanisms to traditional prostate cancer drugs (see pg. 5, para. 4). Gustafson concludes that the hydrophobic tagging strategy adds to the emerging paradigm of induced protein degradation as a therapeutic strategy and may prove useful for the manipulation of disease-relevant proteins that have proven intractable to traditional small molecule approaches (see pg. 5, para. 5).
Gustafson teaches the coupling of a hydrophobic tag to an androgen receptor agonist converts it to a potent Selective Androgen Receptor Degrader (SARD) and discloses that a series of SARDs were designed, as discussed above. Hypothesizing that a SARD only needs to make a transient interaction with AR to enable its ubiquitination, Gustafson tested the activity of SARD279 against proliferating LNCaP cells, demonstrating that SARD279 is capable of degrading AR and inhibiting proliferation even in the presence of higher androgen levels (see pg. 5, para. 2).
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Ying and Gustafson, because both references teach protein targeting and degradation strategies utilizing E3 ligases involved in the UPS pathway to target specific proteins involved in tumor proliferation. One would have recognized from Gustafson the advantage of linking a hydrophobic tag to the protein degradation chimeras of Ying in order to more effectively target disease-associated proteins to the UPS. One would have been particularly motivated to apply this strategy to treat prostate cancer, because Ying teaches this to be an effective strategy in inhibiting androgen-dependent prostate cancer cell lines. As both references teach that Hsp70 and the associated E3 ubiquitin ligase CHIP play a key role in targeting proteins to the UPS, and Gustafson further teaches hydrophobic tags lead to enhanced association with Hsp70, one would have immediately envisaged from the disclosures the use of hydrophobic tags when designing a protein-targeting/degrading chimera. As both disclosures relate to the same components (e.g., Hsp70, CHIP, E3 ligase) and mechanisms (UPS, tumor-targeted protein degradation), and in light of Gustafson’s results using SARDs, including SARD279, one would have recognized there to be a reasonable expectation of success. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 17, Gustafson teaches the PROTAC, SARD279, as discussed above.
Regarding claim 34, Ying teaches the first protein is heat shock protein Hsp70, and Gustafson teaches the PROTAC, SARD279, as discussed above.
Claim(s) 15-16, 31 and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herce and Xu, as applied to claims 1-3, 14, 18, 22, 30, 35 and 37 above, and further in view of Raina (previously cited).
Regarding claim 15, Herce teaches a conjugate, comprising a PROTAC, and a first protein, wherein the PROTAC and the first protein are covalently or non-covalently bonded to each other, wherein the second protein is an E3 ligase, such as Von Hippel-Lindau (VHL), as discussed regarding claim 1. Herce teaches that the first protein (“target protein”) may be a bromodomain and extraterminal domain (BET) protein, as discussed regarding claim 14. Herce also teaches that the chimeras of the disclosure may be used to target a host protein, such as bromodomain 2, bromodomain 3, or bromodomain 4 (see Abstract) which are BET proteins (see pg. 1, para. [0003]).
Herce does not teach wherein the PROTAC is ARV-110, ARV-471, ARV-766, ARV-771, ARV-825, AR-LDD, DT2216, KT-474, KT-413, KT-333, NX-2127, NX-5948, CG001419, CFT8634, FHD-609, or SARD279.
Raina teaches that prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Raina teaches that although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Raina discloses that recently, inhibitors of bromodomain and extraterminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Raina demonstrates that ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. See Abstract.
Raina further discloses that few therapeutic options exist to treat CRPC, especially CRPC tumors expressing constitutively active androgen receptor (AR) splice variants that lack the ligand-binding domain and can effect androgen-independent transactivation of target genes (see pg. 7124, col. 2, “Significance”). Raina teaches that PROTACs, which are chimeric bifunctional small molecules that recruit an E3 ligase to force the destruction of a target protein of interest have been developed by Raina and others as BET protein-targeting agents, and Raina discloses a VHL-based BET targeting PROTAC, ARV-771, which shows high potency of BRD2/3/4 (bromodomain 2, 3, or 4) degradation in several prostate cancer cell lines and has an antiproliferative effect that is up to 500-fold more potent than other BET inhibitors (see pg. 7128, col. 1, para. 2 to col. 2, para. 1).
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Herce and Raina, because both references teach the use of PROTACs to target host proteins, such as BRD 2/3/4, to treat disease. One would have recognized from the results of Raina’s disclosure the advantage of selecting ARV-771 when using PROTAC technology to treat CRPC, because Raina teaches this PROTAC to have dramatically improved antiproliferative effects compared with previous strategies. One would have recognized that both disclosures teach the use of VHL-based PROTACs targeting BET proteins, and Raina further teaches the PROTAC, ARV-771, to be a highly effective solution to treat castration-resistant prostate cancer. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 16, Raina teaches the PROTAC, ARV-771, as discussed above.
Regarding claim 31, Herce teaches the “protein degrader” is a Von Hippel-Lindau (VHL) ligase, and Raina teaches the PROTAC, ARV-771, as discussed above.
Regarding claim 36, Herce teaches the “protein degrader” is CRBN, as discussed regarding claim 35. Raina discloses a CRBN-based PROTAC, ARV-825, which was as potent as ARV-771 in suppressing c-MYC (see pg. 7125, col. 1, para. 3), wherein c-MYC suppression is associated with inhibitor activity against CRPC cells (see pg. 7126, col. 1, para. 2). Hence, it would have been obvious to have selected the CRBN-based PROTAC, ARV-825.
Response to Arguments
Regarding the rejections under 35 U.S.C. 102(a)(2) in view of Herce, Applicant argues that claim 1 has been amended to recite the features of former claim 18, which was not rejected as being anticipated by Herce. Therefore, claim 1 and its dependents are not anticipated by Herce.
Applicant’s arguments have been fully considered and they are persuasive.
Specifically, the examiner agrees that Herce does not teach all of the features required by the claims. Accordingly the rejection has been withdrawn.
Regarding the rejections under 35 U.S.C. 102(a)(1) in view of Ying, Applicant argues that claim 1 has been amended to recite the features of former claim 18, which was not rejected as being anticipated by Ying. Therefore, claim 1 and its dependents are not anticipated by Ying.
Applicant’s arguments have been fully considered and they are persuasive.
Specifically, the examiner agrees that Ying does not teach all of the features required by the claims. Accordingly the rejection has been withdrawn.
Regarding the rejection of claim 18, whose features have now been incorporated into amended claim 1, under 35 U.S.C. 103 in view of Herce and Xu, Applicant argues that, the combination of Herce et al. and Xu et al. discloses PROTACs that bind to a viral protein and a degrader protein. In contrast, the instant application and claims teach that the PROTAC and the degrader protein (e.g., VHL or Hsp70) are complexed (i.e., bonded covalently or non-covalently) to one another prior to encapsulation of the complex. Specification, pg. 20, ¶ 2. Thus, the PROTAC of the prior art combination does not form a ternary complex with the target proteins until after the PROTAC has been internalized by the cell and are silent regarding the pre-complexing of a PROTAC and a degrader protein prior to encapsulation in a lipid nanoparticle.
Applicant's arguments have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “a ternary complex”, “pre-complexing of a PROTAC and a degrader protein” and “complexed prior to encapsulation”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant further argues that Xu discloses the use of approximately 55 compositions comprising one of several cationic lipids and a biomolecule (e.g., saporin or an siRNA), optionally with one or more adjuvants (e.g., cholesterol, DOPE, and/or PEG). Xu et al., Cols. 19 & 20. Specifically, Xu discloses that compositions 33-35 comprise cholesterol, DOPE, as well as the protein. Therefore, the compositions disclosed in the combination of Herce et al. and Xu et al. each require the presence of cholesterol and DOPE to be effective for protein delivery. Therefore, in view of the cited combination of references, one of ordinary skill in the art would be motivated to include cholesterol and DOPE in any subsequent composition to have a reasonable expectation of success. However, no such requirement is recited in the present claims.
Applicant’s arguments have been fully considered but they are not persuasive.
First, the claims recite open language, i.e., “A nanoparticle… comprising a conjugate comprising a proteolysis-targeting chimera (PROTAC), a first protein, and a membrane encapsulating the conjugate…” which does not exclude additional elements. See MPEP 2111.03(I) which states:
The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps… Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) ("Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.)… Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("comprising" leaves "the claim open for the inclusion of unspecified ingredients even in major amounts"). In Gillette Co. v. Energizer Holdings Inc., 405 F.3d 1367, 1371-73, 74 USPQ2d 1586, 1589-91 (Fed. Cir. 2005), the court held that a claim to "a safety razor blade unit comprising a guard, a cap, and a group of first, second, and third blades" encompasses razors with more than three blades because the transitional phrase "comprising" in the preamble and the phrase "group of" are presumptively open-ended. "The word ‘comprising’ transitioning from the preamble to the body signals that the entire claim is presumptively open-ended." Id.
In this case, whether or not cholesterol and DOPE are required for the success of the invention, these elements are not excluded by the claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It should be noted that this also applies to negative limitations.
Moreover, Xu does not necessarily require cholesterol and DOPE, and discloses these elements to be optional, as acknowledged by Applicant. “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 MPEP 2123. In the instant case, Xu’s examples disclose that the lipid-like compound “optionally” included cholesterol and DOPE (see col. 19, lines 22-26) and “Composition 41”, for example, did not comprise these elements at all (see col. 21, line 23; and col. 22, lines 34-38). Therefore, Xu teaches that the inclusion of these adjuvants is optional and discloses embodiments wherein these features are not present.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651