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 .
Please note: applicants stated in the February 10, 2025 response that a complete set of formal drawings in black and white (24 pages) were filed. However, no drawings are present in the response received February 10, 2025.
Status of the Claims
Claims 1-22 were originally filed April 28, 2023.
The amendment received August 12, 2024 amended claims 1 and 6-17; canceled claims 2-5, 9, and 18; and added new claims 23-25.
The amendment received January 29, 2025 amended claims 1, 6, 7, 11, and 13; and canceled claims 2-5, 8-10, 12, 14-16, and 18.
The amendment received January 16, 2026 amended claim 1; canceled claims 6, 7, 11, and 13; and added new claim 26.
Claims 1, 17, and 19-26 are currently pending.
Claims 1, 17, and 23-26 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 1-19) in the reply filed on March 8, 2024. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 20-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim.
Applicants elected, without traverse, PLGA (species A, polymeric matrix), trametinib (species B, first agent), and dabrafenib (applicants incorrectly labeled as species C, second agent) as the species in the reply filed on March 8, 2024. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Please note: applicants neglected to elect species C (what the first agent alters and what the first agent is associated with) or species D (any and all additional components, the function of the components, and what the components are associated with). See the restriction requirement mailed on January 9, 2024; page 5. In order to advance prosecution, the species election is accepted. However, claims that do not read on the elected species (including species that were required but not elected) are withdrawn. Claims 4, 6, 7, 15, 16, 18, and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Applicants’ remarks regarding the species election have been considered. However, applicants failed to elect what the first agent and additional agent were associated with. Therefore, claims 6 and 7 are withdrawn. Claims 15 and 16 are withdrawn because the claims do not read on the elected species of dabrafenib. Claim 19 is withdrawn because applicants neglected to elect a carrier. The election of “any and all additional components” does not limit applicants to a single species of one additional component or to only the “additional agent”. Applicants are free to elect “all additional components” that are part of the polymeric conjugate. Therefore, the failure to elect a “carrier” has caused claim 19 to be withdrawn. It appears that applicants’ representative is confusing “any and all additional components” with the “additional agent”.
Since applicants have amended independent claim 1 with non-elected species to advance prosecution, the amendments have been accepted and are examined. However, applicants may not alter the election of species (e.g. carrier) after an Office Action has been mailed (e.g. election by original presentation). In addition, applicants may not traverse an election after an election without traverse.
In the future, if applicants’ representative “fails to understand what he is required to select”, applicants’ representative should call the examiner of record for clarification prior to submitting a response.
Priority
The present application is a CON of 16/079,123 filed August 23, 2018 (now U.S. Patent 11,666,656) which is a 371 (National Stage) of PCT/IL2017/050236 filed February 24, 2017 which claims the benefit of 62/299,423 filed February 24, 2016.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 17, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Irvine et al. U.S. Patent Application Publication 2014/0377334 published December 25, 2014 and Lacko et al. U.S. Patent Application Publication 2014/0045950 published February 13, 2014.
For present claims 1, 17, and 23-26, Irvine et al. teach compositions comprising PLGA nanoparticles comprising MEK and/or BRAF inhibitors wherein the MEK inhibitors include PD318088 and trametinib and the BRAF inhibitors include sorafenib, dabrafenib, and GDC-0879 and targeting molecules (please refer to the entire specification particularly paragraphs 6-8, 86-97, 105, 120, 136).
However, Irvine et al. does not specifically teach a targeting molecule for P-selectin.
For present claims 1, 17, and 23-26, Lacko et al. teach nanoparticles comprising a P-selectin targeting molecule and dasatinib, imatinib, and/or sorafenib (please refer to the entire specification particularly the abstract; paragraphs 5, 17, 20, 38, 51-54, 84, 86, 114, 116, 124).
The claims would have been obvious because the substitution of one known element (i.e. genus of targeting molecule) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Irvine et al. and Lacko et al. for claims 1, 17, and 23-26 were considered but are not persuasive for the following reasons.
Applicants contend, in the Opening Note (see page 5 of the response received January 16, 2026), that a synergistic effect is present for the nanoparticles comprising DBF and TRM. Applicants also contend in the Opening Note that p-selectin-PLGA-PEG nanoparticles have higher internalization rates.
Applicants contend that Irvine et al. focuses on targeting T cells, is completely silent with regard to two agents acting in synergy together, is silent with regard to selecting therapeutics that would treat melanoma including MEK and/or BRAF inhibitors, and is silent to combining therapeutic agents and targeting moieties to treat melanoma. Applicants contend that since Irvine et al. focuses mostly on T cell targeting and Lacko et al. does not, that the references are non-analogous art. Applicants contend that since Lacko et al. teaches one P-selectin targeting agent within 62 distinct amino acids, that one of skill in the art would not specifically choose a P-selectin targeting agent. Applicants contend that hindsight was utilized. Applicants contend that there is no motivation to combine the references. Applicants contend that since Lacko et al. teach approximately 230 therapeutic agents, that one of skill in the art would not specifically pick any of the MEK and/or BRAF inhibitors taught by Lacko et al. Applicants contend that the declaration previously provided negates the rejection of record.
Applicants’ arguments are not convincing since the teachings of Irvine et al. and Lacko et al. render the polymeric conjugate of the instant claims prima facie obvious.
The present claims are broader in scope than the results in Table 1 (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. In addition, while it appears that the IC50 is improved, cell viability is not synergistic (see Figure 1). It is unclear if the nanoparticles comprise P-selectin.
The present claims are broader in scope than the results in Figures 2A-2C (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. PGLA-PEG nanoparticles are not claimed. The nanoparticles do not comprise any of the claimed first or second agents.
Lacko et al. teaches targeting P-selectin and treating melanoma via targeted nanoparticles with therapeutics attached including dasatinib, imatinib, and/or sorafenib (i.e. all part of the Markush group for the first agent in present independent claim 1; please refer to the entire specification particularly the abstract; paragraphs 5, 54, 84, 114, 116, 124). Lacko et al. defines “targeting molecule” as all molecules capable of specifically binding to a particular target (please refer to the entire specification particularly paragraph 33 for the definition and paragraphs 38-71 for further discussion).
Irvine et al. teaches several of the therapeutics recited in the Markush groups for the first and second agents. Therapeutics of the same structure inherently have the same function (e.g. including a first agent and a second agent working in synergy). Therefore, the mere statement in the claims that the first and second agent work in synergy, does not alter the structure of the first and second agent. If the first and second agent are part of the prior art, the first and second agent would work in synergy (i.e. same structures have the same functions). Working in synergy is a functional limitation and not a structural limitation of the claimed polymeric conjugate.
"Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
The present claims are drawn to a product of a polymeric conjugate. The claims are NOT drawn to a method of treating melanoma.
Irvine et al. specifically teaches that PLGA polymeric particles can comprise RAF (i.e. BRAF) inhibitors and MEK inhibitors including sorafenib, dabrafenib, GDC-0879, PD318088, and trametinib which are all part of the Markush groups in present independent claim 1 (please refer to the entire specification particularly paragraphs 93-97, 105, 120, 136).
Again, the present claims are drawn to a product of a polymeric conjugate. The claims are NOT drawn to a method of treating melanoma.
Irvine et al. states that the compositions employ particles with targeting molecules on the surface that are specific for markers on target cells (please refer to the entire specification particularly paragraph 6). Irvine et al. states that the targeting molecules function to target the particle to a particular cell (please refer to the entire specification particularly paragraph 7). Irvine et al. teaches utilizing the particles to treat cancer (please refer to the entire specification particularly the Drawings; paragraph 8).
"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." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and 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. See 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) and Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998).
Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….". See In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
In order for a reference to be proper for use in an obviousness rejection under 35 USC 103, the reference must be analogous art to the claimed invention. See In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. See Bigio, 381 F.3d at 1325, 72 USPQ2d at 1212.
In response to applicant's argument that Irvine et al. and Lacko et al. are non-analogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992).
Both Irvine et al. and Lacko et al. are drawn to targeted drug delivery vehicles including nanoparticles with targeting molecules and therapeutics (e.g. both teach species within the Markush groups for first and/or second agents recited in independent claim 1) attached. Therefore, both Irvine et al. and Lacko et al. are in the same field of endeavor and both Irvine et al. and Lacko et al. are reasonably pertinent to the problem faced by the inventor.
When the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’"). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
Lacko et al. teaches P-selectin targeting and dasatinib, imatinib, and/or sorafenib (i.e. all part of the Markush group for the first agent in present independent claim 1; please refer to the entire specification particularly the abstract; paragraphs 5, 54, 84, 114, 116, 124).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). See the above rejection.
The claims would have been obvious because the substitution of one known element (i.e. genus of targeting molecule) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). Motivation is not required in the specific prior art references, but can be provided by one of ordinary skill in the art (see above). Here, a person of ordinary skill in the art would hold an advanced degree including a Ph.D. and/or M.D. One of skill in the art could readily ascertain which cells express P-selectin and it was known in the art prior to applicants effective filing date that melanoma cells expressed P-selectin (references will be provided upon request). At no time during prosecution, has the examiner of record suggested that T-cells have P-selectin. Irvine et al. teach targeting molecules and treating melanoma (please refer to the entire specification particularly 3, 7, 92, 137, 156, 158, 160). Lacko et al. teach targeting molecules and treating melanoma (please refer to the entire specification particularly paragraphs 33, 114, and 116).
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).
Regarding the previous Declaration, the Declaration only referred to dabrafenib and trametinib which is not commensurate in scope with the present claims. See MPEP § 716.02(d). It is also respectfully noted that Irvine et al. teach compositions comprising PLGA nanoparticles comprising MEK and/or BRAF inhibitors wherein the MEK inhibitors include trametinib and the BRAF inhibitors include dabrafenib and targeting molecules (please refer to the entire specification particularly paragraphs 6-8, 86-97, 105, 120, 136). Irvine et al. teaches several of the therapeutics recited in the Markush groups for the first and second agents. Therapeutics of the same structure inherently have the same function (e.g. including a first agent and a second agent working in synergy). "Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Regarding present claim 25, the prior art of record teaches the presently claimed combination of trametinib and dabrafenib in a single reference in combination with PLGA nanoparticles. Thus, the synergistic property would be present in a single reference. The utilization of a specific targeting molecule could be readily chosen by one of skill in the art dependent on which cells are to be targeted.
Claims 1, 17, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Surber U.S. Patent Application Publication 2015/0044288 published February 12, 2015; Irvine et al. U.S. Patent Application Publication 2014/0377334 published December 25, 2014; and Lacko et al. U.S. Patent Application Publication 2014/0045950 published February 13, 2014.
For present claims 1, 17, and 23-26, Surber teaches compositions comprising PLGA nanoparticles or microparticles comprising MEK inhibitors including trametinib and selumetinib in combination with BRAF inhibitors including vemurafenib, dabrafenib, sorafenib, GSC-0879, and LGX818 (please refer to the entire specification particularly paragraphs 249, 250, 253, 256, 259, 377, 443, 503-510, 514, 519, 523, 538-548).
However, Surber et al. do not teach a P-selectin targeting molecule.
For present claims 1, 17, and 23-26, Irvine et al. teach compositions comprising PLGA nanoparticles comprising MEK and/or BRAF inhibitors wherein the MEK inhibitors include PD318088 and trametinib and the BRAF inhibitors include sorafenib, dabrafenib, and GSC-0879 and targeting molecules (please refer to the entire specification particularly paragraphs 6-8, 86-97, 105, 120, 136).
For present claims 1, 17, and 23-26, Lacko et al. teach nanoparticles comprising a P-selectin targeting molecule and dasatinib, imatinib, and/or sorafenib (please refer to the entire specification particularly the abstract; paragraphs 5, 17, 20, 38, 51-54, 84, 86, 114, 116, 124).
The claims would have been obvious because a particular known technique (i.e. adding targeting molecules to nanoparticles comprising therapeutics to target specific cells) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (i.e. genus of targeting molecule) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Surber; Irvine et al.; and Lacko et al. for claims 1, 17, and 23-26 were considered but are not persuasive for the following reasons.
Applicants contend, in the Opening Note (see page 5 of the response received January 16, 2026), that a synergistic effect is present for the nanoparticles comprising DBF and TRM. Applicants also contend in the Opening Note that p-selectin-PLGA-PEG nanoparticles have higher internalization rates.
Applicants contend that Surber focuses on aerosolized inhalation formulations, does not provide guidance to specifically select MEK and/or BRAF inhibitors from an extensive list of anti-cancer agents, does not teach selecting two anti-cancer agents that act in synergy, or how a nebulization formulation would treat melanoma. Applicants state that Surber utilizes inhaled delivery of drug formulations to target desired anatomical sites which teaches away from utilizing a targeting moiety. Applicants contend that Irvine et al. only refers to systemic delivery. Applicants contend that there is no motivation to combine the references.
Applicants’ arguments are not convincing since the teachings of Surber; Irvine et al.; and Lacko et al. render the polymeric conjugate of the instant claims prima facie obvious.
The present claims are broader in scope than the results in Table 1 (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. In addition, while it appears that the IC50 is improved, cell viability is not synergistic (see Figure 1). It is unclear if the nanoparticles comprise P-selectin.
The present claims are broader in scope than the results in Figures 2A-2C (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. PGLA-PEG nanoparticles are not claimed. The nanoparticles do not comprise any of the claimed first or second agents.
The present claims are drawn to a polymeric conjugate. The present claims are NOT drawn to a method of treating melanoma. No where in the claims are aerosolized formulations negated. The polymeric compositions may be in any form for administration as presently claimed. In addition, even if the claims did negate aerosolized formulations, the claims would have to clearly delineate the structure which would be different in the claims.
Surber teaches compositions comprising PLGA nanoparticles or microparticles comprising MEK inhibitors including trametinib and selumetinib in combination with BRAF inhibitors including vemurafenib, dabrafenib, sorafenib, GDC-0879, and LGX818 (please refer to the entire specification particularly paragraphs 249, 250, 253, 256, 259, 377, 443, 503-510, 514, 519, 523, 538-548). The specific therapeutics disclosed by Surber are part of the Markush groups for the first and second agents recited in present independent claim 1. Therapeutics of the same structure inherently have the same function (e.g. including a first agent and a second agent working in synergy).
"Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
When the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’"). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
Irvine et al. teach utilizing targeting molecule on nanoparticles and Lacko et al. specifically teach utilizing targeting molecules that target P-selectin on nanoparticles (see the above rejection for paragraph numbers).
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).
Surber utilizes inhaled delivery to increase target organ dose, pharmacokinetic profile, safety profile, efficacy, and safety and to reduce patient resistance (please refer to the entire specification particularly paragraph 3). This does not preclude or dissuade one of skill in the art from also utilizing a targeting moiety.
"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." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and 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. See 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) and Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998).
Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….". See In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Systemic delivery includes pulmonary delivery.
Systemic Delivery means the administration of a drug product systemically in the body of the patient, including by intravenous, subcutaneous, oral or pulmonary administration. Administration of a drug product to the eye or its adnexa through a Drug Delivery System shall not be deemed to be Systemic Delivery.
Systemic administration refers to the delivery of a substance, such as a drug or nanoparticle, through various routes that allow it to enter the bloodstream and circulate throughout the body. This can include intraperitoneal injections, digestive tract or lung administration, transdermal administration, intranasal, intraperitoneal, retro-orbital sinus, and tail vein injections. The goal of systemic administration is to expose more tissues to the substance, but this also means that the substance will be widely dispersed throughout the body.
Furthermore, it is art recognized that melanoma may be treated with aerosol delivery. See Hu et al., 2011, Anticancer properties of 10-hydroxycamptothecin in a murine melanoma pulmonary metastasis model in vitro and in vivo, Toxicology in Vitro, 25: 513-520 and Posch et al., 2014, Low-dose inhalation of interleukin-2 bio-chemotherapy for the treatment of pulmonary metastases in melanoma patients, British Journal of Cancer, 110: 1427-1432.
The claims would have been obvious because a particular known technique (i.e. adding targeting molecules to nanoparticles comprising therapeutics to target specific cells) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (i.e. genus of targeting molecule) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). Motivation is not required in the specific prior art references, but can be provided by one of ordinary skill in the art (see above). Here, a person of ordinary skill in the art would hold an advanced degree including a Ph.D. and/or M.D. One of skill in the art could readily ascertain which cells express P-selectin and it was known in the art prior to applicants effective filing date that melanoma cells expressed P-selectin (references will be provided upon request). At no time during prosecution, has the examiner of record suggested that T-cells have P-selectin. Irvine et al. teach targeting molecules and treating melanoma (please refer to the entire specification particularly 3, 7, 92, 137, 156, 158, 160). Lacko et al. teach targeting molecules and treating melanoma (please refer to the entire specification particularly paragraphs 33, 114, and 116).
Regarding present claim 25, the prior art of record teaches the presently claimed combination of trametinib and dabrafenib in a single reference in combination with PLGA nanoparticles. Thus, the synergistic property would be present in a single reference. The utilization of a specific targeting molecule could be readily chosen by one of skill in the art dependent on which cells are to be targeted.
See the above arguments regarding Irvine et al. and Lacko et al.
Claims 1, 17, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al., 2015, Recent Advances in targeted nanoparticles drug delivery to melanoma, Nanomedicine: Nanotechnology, Biology, and Medicine, 11: 769-794 and Lacko et al. U.S. Patent Application Publication 2014/0045950 published February 13, 2014.
For present claims 1, 17, and 23-26, Li et al. teach PLGA particles comprising multiple melanoma therapies including dabrafenib and trametinib and active targeting ligands (please refer to the entire reference particularly the abstract; introduction; Figure 1; Tables 1, 3, and 4; “Combination therapy” section).
However, Li et al. does not specifically teach a targeting molecule for P-selectin.
For present claims 1, 17, and 23-26, Lacko et al. teach nanoparticles comprising a P-selectin targeting molecule and dasatinib, imatinib, and/or sorafenib (please refer to the entire specification particularly the abstract; paragraphs 5, 17, 20, 38, 51-54, 84, 86, 114, 116, 124).
The claims would have been obvious because the substitution of one known element (i.e. genus of active targeting ligands) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Li et al. and Lacko et al. for claims 1, 17, and 23-26 were considered but are not persuasive for the following reasons.
Applicants contend, in the Opening Note (see page 5 of the response received January 16, 2026), that a synergistic effect is present for the nanoparticles comprising DBF and TRM.
Applicants also contend in the Opening Note that p-selectin-PLGA-PEG nanoparticles have higher internalization rates.
Applicants contend that Li et al. do not teach any specific formulation, do not teach P-selectin, and do not teach a synergistic combination of MEK and/or BRAF inhibitors.
Applicants’ arguments are not convincing since the teachings of Li et al. and Lacko et al. render the polymeric conjugate of the instant claims prima facie obvious.
The present claims are broader in scope than the results in Table 1 (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. In addition, while it appears that the IC50 is improved, cell viability is not synergistic (see Figure 1). It is unclear if the nanoparticles comprise P-selectin.
The present claims are broader in scope than the results in Figures 2A-2C (Declaration filed August 12, 2024). Unexpected results must be commensurate in scope with the present claims. PGLA-PEG nanoparticles are not claimed. The nanoparticles do not comprise any of the claimed first or second agents.
The present claims are drawn to a polymeric conjugate. The present claims are NOT drawn to a method of treating melanoma.
Li et al. teach PLGA particles comprising multiple melanoma therapies including dabrafenib and trametinib (i.e. species in the Markush group as claimed in present independent claim 1) and active targeting ligands (please refer to the entire reference particularly the abstract; introduction; Figure 1; Tables 1, 3, and 4; “Combination therapy” section). Therefore, the same combination of dabrafenib and trametinib would necessarily have the same synergistic properties.
"Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Lacko et al. teach nanoparticles comprising a P-selectin targeting molecule and dasatinib, imatinib, and/or sorafenib (please refer to the entire specification particularly the abstract; paragraphs 5, 17, 20, 38, 51-54, 84, 86, 114, 116, 124).
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).
When the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’"). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
The claims would have been obvious because the substitution of one known element (i.e. genus of active targeting ligands) for another (i.e. species of a P-selectin targeting molecule) would have yielded predictable results (i.e. targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). Motivation can come from one of skill in the art and not expressly stated in the prior art references. In addition, one of skill in the art would hold an advanced degree including a Ph.D. and/or M.D.
In order for a reference to be proper for use in an obviousness rejection under 35 USC 103, the reference must be analogous art to the claimed invention. See In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. See Bigio, 381 F.3d at 1325, 72 USPQ2d at 1212.
Li et al. and Lacko et al. both teach nanoparticles with therapeutics and targeting moieties. Thus, the references are in the same field of endeavor and reasonably pertinent to the problem faced by the “inventor” (i.e. applicants).
Regarding present claim 25, the prior art of record teaches the presently claimed combination of trametinib and dabrafenib in a single reference in combination with PLGA nanoparticles. Thus, the synergistic property would be present in a single reference. The utilization of a specific targeting molecule could be readily chosen by one of skill in the art dependent on which cells are to be targeted.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 17, and 23-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,666,656 in view of Irvine et al. U.S. Patent Application Publication 2014/0377334 published December 25, 2014 and Lacko et al. U.S. Patent Application Publication 2014/0045950 published February 13, 2014.
U.S. Patent No. 11,666,656 claims polymeric conjugates comprising a matrix comprising a plurality of PLGA particles comprising selumetinib and dabrafenib and a targeting moiety.
U.S. Patent No. 11,666,656 does not teach trametinib.
Irvine et al. teach compositions comprising PLGA nanoparticles comprising MEK and/or BRAF inhibitors wherein the MEK inhibitors include PD318088 and trametinib and the BRAF inhibitors include sorafenib, dabrafenib, and GSC-0879 and targeting molecules (please refer to the entire specification particularly paragraphs 6-8, 86-97, 105, 120, 136).
U.S. Patent No. 11,666,656 does not teach a P-selectin targeting moiety.
Lacko et al. teach nanoparticles comprising a P-selectin targeting molecule and dasatinib, imatinib, and/or sorafenib (please refer to the entire specification particularly the abstract; paragraphs 5, 17, 20, 38, 51-54, 84, 86, 114, 116, 124).
The claims would have been obvious because the substitution of one known element (i.e. one cancer therapeutic; genus of active targeting molecule) for another (i.e. another cancer therapeutic; species of a P-selectin targeting molecule) would have yielded predictable results (i.e. nanoparticles with a specific combination of cancer therapeutics; targeting cells expressing P-selectin) to one of ordinary skill in the art at the time of the invention. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,666,656 in view of Irvine et al. and Lacko et al. for claims 1, 17, and 23-26 were considered but are not persuasive for the following reasons.
Applicants contend that the examiner should look to the arguments for the 35 USC 103 rejections and that the rejection should be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,666,656 in view of Irvine et al. and Lacko et al. renders obvious the polymeric conjugate of the instant claims. See the response to the 35 USC 103 rejection above. Applicants should address each rejection in full particularly when the rejections have different references applied (i.e. U.S. Patent No. 11,666,656). In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Patent Application Publications 2013/0310424 and 2014/0248211
Robert et al., 2015, Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib, The New England Journal of Medicine, 372(1): 30-39.
Additional art:
U.S. Patent Application Publication 2023/0201127
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.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658