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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 18, 2026 has been entered.
Applicants' arguments, filed March 18, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Claim Interpretation
Claims 38, 39, and 48 – 54 clearly recite the behavior of the claimed shielding agent after administration, namely that the shielding agent binds to PSMA (prostate-specific membrane antigen) expressing non-cancerous cells in various locations throughout the body. Such behavior is determined by the structure of the administered shielding agent. The combination of applied prior art renders obvious the elected species as discussed in greater detail below that is amongst the structures recited in the instant claims. There is no evidence of record that the elected species does not bind to PSMA on these non-cancerous cells and therefore these claims are not patentably distinguished over prior art that renders obvious the administration of such compounds to a subject in need of cancer treatment as claimed even if the prior art does not explicitly describe such binding behavior. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 47 and 51 – 54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims 47 and 51, from which claims 52 – 54 depend, recites a generic step of blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell using any compound, in contrast to claim 48 that recites that the shielding agent binds to PSMA expressed on a non-cancerous cell, specifying the compound that blocks such binding. Therefore the scope of the compounds that block such binding is defined solely by function in claims 47 and 51 – 54.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus. Not every species within a genus must be disclosed and the written description requirement can be satisfied by the disclosure of a representative number of species within the claimed genus.
The specification as filed indicates that in some embodiments the shielding agents are examples of compounds that can block such binding (¶¶ [0104] and [0105]). Some examples are given, particularly in table 1. There is also an incorporation by reference statement to two journal articles at ¶ [0104] of the PGPub of the instant application, and if those compounds have this function, this results in an improper incorporation by reference as the scope of compounds that have this function is essential subject matter and essential subject matter can only be incorporated by reference to U.S. patent documents.
But the scope of the rejected claims is broader than the compounds disclosed in the application as filed and while there some different common structures in the compounds disclosed, these compounds are not a representative number of species within the claimed genus of compounds or actions that can be taken to block the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell as required by these claims.
The dependent claims fall therewith.
Claim Rejections - 35 USC § 112 – New Matter
Claims 47 and 51 – 54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The disclosure as originally filed does not disclose the use of any compound or method to block the binding of the radiolabeled therapeutic that binds to PSMA expressed on a non-cancerous cells. ¶¶ [0104] and [0105] disclose that the shielding agents can have such an effect but the scope of the rejected claims is broader, encompassing any compound that has such a property.
If Applicant is in disagreement with the Examiner regarding support for the amended claims, Applicant is respectfully requested to point to page and line number wherein support may be found for the instant invention.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 47 – 49 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.
As discussed in the application as filed, the arguments and instant claim 48, the shielding compound such as those recited in claim 2 bind to PMSA (prostate specific membrane antigen) expressed on a non-cancerous cell, an inherent characteristic arising from the structure of the claimed compounds, which are completely specified by the claims.
Claim 47 depends from claim 2 that requires the administration of a shielding agent. However, claim 47 recites that the method “further comprises blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell” (emphasis added). The shielding agents of claim 2 inherently have this ability, but the phrasing of “further comprises” suggests that claim 47 requires administration of something more in addition to that required by claim 2. This phrasing seems to indicate that additional step and/or compound beyond those already required by claim 2 is required. Does claim 47 require the administration of any compound, not necessarily one of the shielding agents of claim 2, to the subject in addition to the two compounds required by claim 2? Such a step does not appear to be supported by the disclosure as originally filed both in terms of new matter and written description for the full scope of actions and/or compounds that can be taken to block the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell.
The dependent claims fall therewith.
Please clarify.
Claims 51 – 54 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.
The step of “sequentially administering to the patient a therapeutically effective amount of a radiolabeled therapeutic that binds prostate specific membrane antigen (PSMA) in combination with an effective amount of a shielding agent that binds PSMA” (emphasis added) recited in calm 51 is not clear.
If the two agents are administered sequentially, one must be administered before the other and either order of administration would be encompassed. But the phrase then goes on to refer to a “combination” which would appear to be a composition that contains both ingredients, which cannot be administered sequentially, as the administration of the composition containing both ingredients results in all the elements of the composition being delivered at the same time.
Therefore it is not clear if two sequential administration steps, one for the radiolabeled therapeutic that binds to PSMA and one for the shielding agent, is required by claim 51 or if a single administration step of a composition containing both the radiolabeled therapeutic that binds to PSMA and shielding agent falls within the scope of the claims.
The dependent claims fall therewith.
Please clarify.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 4 – 6, 38, 39 and 47 – 54 were rejected under 35 U.S.C. 103 as being unpatentable over Slusher et al. (US 2017/0226141) in view of Koseki et al. (Bull Chem Soc Jpn, 2016) and Eder et al. (US 2016/0228587). This rejection is MAINTAINED for the reasons of record set forth herein.
Slusher et al. discloses compounds of formula (I) or (II) (¶ [0005] onward) and methods of treating a disease or condition comprising administering to a subject in need of such treatment a compound of formula (I) or pharmaceutical compositions thereof (¶ [0018]). The disease or condition can be cancer (¶ [0019]) and in some aspects the disease or condition results in excess PSMA activity and the method further comprises inhibiting the excess PSMA activity when the compound of formula (I) or (II) is administered (¶ [0021]; see also claims 28 – 32). Compounds of formula (I) are shown at ¶ [0005] and when R1 = R3 = R4 = H and R2 = alkyl chain, such compounds are structurally homologous to the elected shielding agent and the other phosphate containing compounds of instant claims such as claims 2 and 8. In particular embodiments, “alkyl” refers to C1-20, inclusive, carbon chains (¶ [0133]). 2-PMPA is a highly polar compound with multiple carboxylates and a zinc binding phosphonate group with negligible oral bioavailability (¶ [0055]). This issue can be solved by making the polar groups less polar although typical groups such as the lower alkyls methyl, ethyl and propyl were not successful due to the excess stability of these groups so alternative groups were used to provide the right balance of lability in vitro and highest doses delivered after oral administration (¶ [0055]). The compounds disclosed are effective over a wide dosage range with the exact dosage depending upon the route of administration, the subject to be treated and the preference and experience of the attending physician and some example ranges such as 0.01 – 1000 mg are given (¶ [0102]).
Compounds of formula (I) with an alkyl chain as R2 are not explicitly disclosed that can be viewed as containing a fatty acid ester moiety.
Koseki et al. discloses that nanodrugs have received considerable attention due to their potential application cancer therapy as they can accumulate in within tumors with leak vasculature (p 540, col 1). The use of pure nanodrugs can overcome issues such as low drug loading ratios and side effects from the nanocarriers or metabolites when nanocarriers are used (p 540, col 1). Prodrug molecules with hydrophobic substituent groups are used as nano-prodrugs (p 540, col 2, ¶ 1). The fatty acid carbon chain length was expected to alter the particle size and also the hydrolysis rate due to the protective effect of the ester bond on the bulky substituent group (p 540, col 2, ¶ 1). The model compound used was the well-known anti-cancer agent SN-38 and was esterified with C6, C10, C14, C18 or C18:1 fatty acids (p 543, col 1, ¶ 2 and figure 1). All of the prepared ester linked prodrugs showed higher cytotoxicity than the clinically used prodrug of SN-38 called irinotecan with decreasing cytotoxicity as the fatty acid carbon chain length increased (p 543, col 2, ¶ 2). When looking at cellular uptake of the SN-38 nano-prodrugs, increasing fatty acid chain length resulted in increased cellular uptake indicating that lipophilicity affected cellular uptake efficiency (p 544, col 1, ¶ 2 and table 1). Prodrugs with fatty acid chain longer than 10 were more resistant hydrolysis in the presence of porcine level esterase (PLE) and the nano-prodrugs with C2, C6 and C10 fatty acid chains were readily hydrolyzed within 0.5 hours, suggesting that fatty acid chain length affects the hydrolysis rate within cancer cells (¶ bridging p 544 and 545). The in vitro cytotoxicity was critically dependent on the hydrolysis rate and the nano-prodrugs should be designed to resist hydrolysis in the blood and circulate for a longer time to increase the possibility of interaction with cancer sites and the results suggest longer chain fatty acids produced more hydrolysis-resistant nano-prodrugs that could be promising candidates for cancer therapy (p 545, col 1, ¶ 2).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a compound of formula (I) of Slusher et at. with a longer alkyl chain such as C12 which fall within the scope of compounds of formula (I) of Slusher et al. and can aid in the formation of particles of the compound as taught by Koseki et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such compounds fall within the scope of formula (I) of Slusher et al. and can be administered to treat diseases or conditions such as cancer and/or those resulting in excess PMSA activity. Koseki et al. uses longer alkyl chains than those that were disclosed as not effective in Slusher et al. and one of ordinary skill in the art would optimize the alkyl chain length in the compounds of formula (I) in Slusher et al. As taught by Koseki et al., the fatty acid chain length affects cytotoxicity, cellular uptake and ester hydrolysis that is critical to the toxicity of the administered agent. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal fatty acid chain length when preparing a compound of formula (I) that can then be administered to a subject to treat a disease such as cancer as taught by Slusher et al. There is no evidence of record that the doses of such a compound used to treat cancer do not fall within the range of an effective amount of shielding agent as required by the instant claims as one of ordinary skill in the art would optimize the dosage of the drug using the considerations discussed by Slusher et al. such as the route of administration, the subject to be treated and the preference and experience of the attending physician.
The administration of a radiolabeled therapeutic such as the 117Lu containing compound of instant claims 2 and 51 is not disclosed.
Eder et al. discloses radiopharmaceuticals and their use as imaging agents or to treat various disease states of prostate cancer (whole document, e.g., abstract). Prostate cancer (PCa) is the leading cancer in the US and European population but there is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer (¶ [0004]). Androgen-independent prostate cancer is used synonymously with castration resistant prostate cancer (CRPC) and CRPC is the preferred and recommended term (see p 189, col 1, ¶ 1 of Bellmunt et al., Ther Adv Med Oncol, 2010). Almost all PCs become androgen independent over time, increasing the importance of PMSA which has abundant and restricted expression to prostate expression at all stages of the disease (¶ [0007]). The object of the invention is to provide ligands that interact with PMSA and carry appropriate radionuclides which provide a promising and novel targeting option for detection, treatment and management of prostate cancer (¶ [0012]). The cancer can be prostate cancer or prostate cancer metastasis to organs such as lung and liver (¶ [0078]). Preferred compounds of the invention include the compound MB17 on the lower right portion of p 6 which is the radiolabeled compound of the instant claims. Human therapy with a Lu-177 labeled version of MB17 was administered to patients in example 10 at ¶ [0128].
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject with prostate cancer that such as one with metastatic cancer that has become castration resistant/androgen independent with a radiolabeled compound such as the 177Lu-MB17 of Eber et al. in combination with the compound of formula (I) of Slusher et al. and Koseki et al. of a fatty acid prodrug of 2-PMPA. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Both agents are taught for the treatment of PMSA associated conditions and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer with both agents since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition. “Selection of any order of process steps is prima facia obvious in the absence of new or unexpected results.” See MPEP § 2144.04, IV. Therefore it would have been obvious to give one drug before the other (sequential administration) or to administer them together in a single combination to minimize the number of administration steps required to deliver both agents to a subject. There is no evidence of record as to new or unexpected results arising from the order of administration of the two different compounds.
As to the location of binding of the shielding agent of the instant claims upon administration, this necessarily flows from the structure of the compound that determines the in vivo binding behavior of each compound when administered. While binding to PSMA expressed on non-cancerous cells such as those of the tissues recited in claims 39 and 49 is not explicitly disclosed by the prior art, that is not required to render the claims obvious as the therapeutic activities of both compounds renders obvious administration of both agents to a subject with cancer such as prostate cancer. The administration of both of the claimed compounds to a subject having cancer that expresses PSMA, the binding target of the compounds being administered for the administered active agents, is rendered obvious. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Therefore the explicit recitation in the claims of a compound such as the shielding agent blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell does not patentably distinguish the instant claims over the applied prior art.
Applicants traverse this rejection on the grounds that a person of ordinary skill in the art would not have been motivated to combine Slusher or modified Slusher to arrive at the claimed invention with any reasonable expectation of success. Slusher provides no suggestion that the disclosed prodrug compounds would behave as a shielding agent, particularly in combination with an additional therapeutic agent such as a radiolabeled therapeutic agent. As the claims are presently amended, the effect by the claimed radiolabeled therapeutic and shielding agent is described in the specification and examples, with one graph showing the results from one figure reproduced in the remarks. There is a greater decrease in the biodistribution of compounds Ia-Lu in the kidney with shielding agents 1d and 1m than in the tumor tissue. This enhanced selectivity effect is because the shielding agent preferentially decreases the binding of the radioligand to non-target (non-tumor) tissue. This effect is not what would have been contemplated by the person of ordinary skill as both references contemplate the therapeutic effect of the compositions as a result of binding to PSMA.
These arguments are unpersuasive. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (see MPEP 2144(IV)). The relevant question for obviousness is if one of ordinary skill in the art would have been motivated to administer both the radiolabeled compound, 177Lu-MB17 of Eber et al. and a compound as set forth in claim 2 that the instant application labels as a shielding agent that are also lipid prodrugs on 2-PMPA as taught by Slusher et al. and Koseki et al. to a subject with cancer that expresses PSMA such as prostate cancer. One of ordinary skill in the art would be motivated as both agents are taught for the same purpose in the art as discussed above. That the instant claims administer compounds of the same structure for “shielding” rather than a therapeutic effect does not patentably distinguish the instant claims as the same compounds are administered to the same patient population as claimed and there is no evidence that therapeutic doses do not provide the required blocking effect on non-cancerous cells expressing PSMA.
Applicants also argue that this combination provides improved therapy for the treatment of PSMA expressing cancer based on enhanced selectivity of the radiotherapeutic to the target tumor. Evidence of secondary considerations can show nonobviousness. The effect provided by the combination in the claims is supported by evidence in the specification with specific shielding agents providing an enhanced ratio of tumor to kidney biodistributions, showing the surprising improvement in the selective targeting of cancer cells over non-cancer cells that could not have been reasonably predicted based on the alleged combination of prior art.
These arguments are unpersuasive. Please see MPEP 716.02 et seq. for a complete discussion of unexpected results. Applicants bear the burden of establishing what the expected results would be to determine if the observed results are in fact unexpected. Both compounds are taught to bind to PSMA and there must be differences between PSMA on tumor cells and those on non-cancer cells to give rise to stated differential binding. Given the differences in the structures of the two different compounds administered that determine their binding behavior, the evidence of record has not established that one of ordinary skill in the art would expect both compounds to bind identically to tumor and non-tumor PSMA expressing cells has not been established. The evidence must also be reasonably commensurate in scope with the claims. The Examiner was unable to locate any data for the enantiomers of compound 1d in claims and several of compounds recited in claim 51. Finally, the evidence of record in support of the alleged unexpected results must be weighed against the prima facie case of obviousness. When the record as a whole is evaluated and weighed against the prima facie case of obviousness, the evidence in support of the alleged unexpected results does not outweigh the prima facie case of obviousness and the rejection is maintained.
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.
The provisional nonstatutory double patenting rejections over U.S. Application Nos. 17/737,471, 17/904,442, 18/958,358, 18/958,394 and 18/958,413 have been withdrawn as each of these applications have been abandoned.
Regarding the remaining rejections from the previous Office Action that have not been withdrawn, Applicants traverse on the same grounds set forth above regarding Slusher, Koseki and Eder above.
As discussed in greater detail above, the arguments regarding Slusher, Koseki and Eder above are not persuasive and the previous rejections are maintained for the reasons of record.
Claims 2, 4 – 6, 38, 39 and 47 – 54 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 and 11 of U.S. Patent No. 9,988,407 [This is the patent that issued from the application of PGPub 2017/0226141 used in the obviousness rejection above] in view of Koseki et al. (Bull Chem Soc Jpn, 2016) and Eder et al. (US 2016/0228587). This rejection is MAINTAINED for the reasons of record set forth herein.
The claims of US’407 recite compounds of formula (I) as defined in claim 1. These compounds can be used in a method for treating a disease or condition such as colon cancer or prostate cancer (claim 9).
That R2 is an alkyl and R1 = R3 = R4 = H which results in a shielding compound as in instant claim 2 is not explicitly claimed.
Koseki et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a compound of formula (I) of US’407 with a longer alkyl chain such as C12 which fall within the scope of compounds of formula (I) of US’407 and can aid in the formation of particles of the compound as taught by Koseki et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such compounds fall within the scope of formula (I) of US’407 and can be administered to treat diseases or conditions such as cancer and/or those resulting in excess PMSA activity. One of ordinary skill in the art would optimize the alkyl chain length in the compounds of formula (I) in US’407. As taught by Koseki et al., the fatty acid chain length affects cytotoxicity, cellular uptake and ester hydrolysis that is critical to the toxicity of the administered agent. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal fatty acid chain length when preparing a compound of formula (I) that can then be administered to a subject to treat a disease such as cancer as claimed in US’407. There is no evidence of record that the doses of such a compound used to treat cancer do not fall within the range of an effective amount of shielding agent as required by the instant claims as one of ordinary skill in the art would optimize the dosage of the drug using the considerations discussed by Slusher et al. such as the route of administration, the subject to be treated and the preference and experience of the attending physician
The administration of a radiolabeled therapeutic such as the 117Lu containing compound of the instant claims such as for the treatment of metastatic castration resistant prostate cancer is not disclosed.
Eder et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject with prostate cancer that such as one with metastatic cancer that has become castration resistant/androgen independent with a radiolabeled compound such as the 177Lu-MB17 of Eber et al. in combination with the optimized compounds of formula (I) of US’407 and Koseki et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Both agents are taught for the treatment of PMSA associated conditions and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer such as metastatic castration resistant prostate cancer with both agents since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition. “Selection of any order of process steps is prima facia obvious in the absence of new or unexpected results.” See MPEP § 2144.04, IV. Therefore it would have been obvious to give one drug before the other (sequential administration) or to administer them together in a single combination to minimize the number of administration steps required to deliver both agents to a subject. There is no evidence of record as to new or unexpected results arising from the order of administration of the two different compounds.
As to the location of binding of the shielding agent of the instant claims upon administration, this necessarily flows from the structure of the compound that determines the in vivo binding behavior of each compound when administered. While binding to PSMA expressed on non-cancerous cells such as those of the tissues recited in claims 39 and 49 is not explicitly disclosed by the prior art, that is not required to render the claims obvious as the therapeutic activities of both compounds renders obvious administration of both agents to a subject with cancer such as prostate cancer. The administration of both of the claimed compounds to a subject having cancer that expresses PSMA, the binding target of the compounds being administered for the administered active agents, is rendered obvious. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Therefore the explicit recitation in the claims of a compound such as the shielding agent blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell does not patentably distinguish the instant claims over the applied prior art.
Claims 2, 4 – 6, 38, 39 and 47 – 54 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30 - 49 of copending Application No. 18/906,001 in view of Slusher et al. (US 2017/0226141) and Koseki et al. (Bull Chem Soc Jpn, 2016) and optionally further in view of Eder et al. (US 2016/0228587). This rejection is MAINTAINED for the reasons of record set forth herein.
The claims of US’ 001 recite compounds B-L-D that are encompassed by the therapeutic agent of the instant claims. B is a PSMA binding region, L is a linker and D is radioactive isotope of metal coordinated to a chelating group, reading on the therapeutic agent of the instant claims.
Co-administration with a compound such as the shielding agents of the instant claims is not claimed.
Slusher et al. and Koseki et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to compound of formula (I) of Slusher et at. with a longer alkyl chain such as C12 which fall within the scope of compounds of formula (I) of Slusher et al. and can aid in the formation of particles of the compound as taught by Koseki et al. which is administered with the therapeutic agents of US’001. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such compounds fall within the scope of formula (I) of Slusher et al. and can be administered to treat diseases or conditions such as cancer and/or those resulting in excess PMSA activity. Koseki et al. uses longer alkyl chains than those that were disclosed as not effective in Slusher et al. and one of ordinary skill in the art would optimize the alkyl chain length in the compounds of formula (I) in Slusher et al. As taught by Koseki et al., the fatty acid chain length affects cytotoxicity, cellular uptake and ester hydrolysis that is critical to the toxicity of the administered agent. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal fatty acid chain length when preparing a compound of formula (I) that can then be administered to a subject to treat a disease such as cancer as taught by Slusher et al. There is no evidence of record that the doses of such a compound used to treat cancer do not fall within the range of an effective amount of shielding agent as required by the instant claims as one of ordinary skill in the art would optimize the dosage of the drug using the considerations discussed by Slusher et al. such as the route of administration, the subject to be treated and the preference and experience of the attending physician. The person of ordinary skill in the art also would have been motivated to use the combination of agents and reasonably would have expected success because the agents are useful for the treatment of conditions associated with PMSA such as prostate cancer. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Both agents are taught for the treatment of PMSA associated conditions and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer with both agents as in US’001 and Slusher et al. in combination with Koseki et al. since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition.
The treatment of specific types of prostate cancer is not claimed.
Eder et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject with prostate cancer that such as one with metastatic cancer that has become castration resistant/androgen independent with a radiolabeled compound such as the 177Lu-MB17 of Eber et al. (the compound of instant claim 3) in combination with the optimized compounds of formula (I) of Slusher et al. and Koseki et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease including the castration resistant form of metastatic prostate cancer. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer such as metastatic castration resistant prostate cancer with both agents since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition. “Selection of any order of process steps is prima facia obvious in the absence of new or unexpected results.” See MPEP § 2144.04, IV. Therefore it would have been obvious to give one drug before the other (sequential administration) or to administer them together in a single combination to minimize the number of administration steps required to deliver both agents to a subject. There is no evidence of record as to new or unexpected results arising from the order of administration of the two different compounds.
As to the location of binding of the shielding agent of the instant claims upon administration, this necessarily flows from the structure of the compound that determines the in vivo binding behavior of each compound when administered. While binding to PSMA expressed on non-cancerous cells such as those of the tissues recited in claims 39 and 49 is not explicitly disclosed by the prior art, that is not required to render the claims obvious as the therapeutic activities of both compounds renders obvious administration of both agents to a subject with cancer such as prostate cancer. The administration of both of the claimed compounds to a subject having cancer that expresses PSMA, the binding target of the compounds being administered for the administered active agents, is rendered obvious. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Therefore the explicit recitation in the claims of a compound such as the shielding agent blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell does not patentably distinguish the instant claims over the applied prior art.
This is a provisional nonstatutory double patenting rejection.
Claims 2, 4 – 6, 38, 39 and 47 – 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 38 - 57 of copending Application No. 18/999,436 in view of Slusher et al. (US 2017/0226141) and Koseki et al. (Bull Chem Soc Jpn, 2016).
The claims of US’436 recite a method of treating castration resistant prostate cancer with compound 1 of claim 38 labeled with 177Lu (claim 1), which is compound Ia of instant claim 2.
Co-administration with a compound such as the shielding agents of instant claim 2 is not claimed.
Slusher et al. and Koseki et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to compound of formula (I) of Slusher et at. with a longer alkyl chain such as C12 which fall within the scope of compounds of formula (I) of Slusher et al. and can aid in the formation of particles of the compound as taught by Koseki et al. which is administered with the therapeutic agents of US’457. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such compounds fall within the scope of formula (I) of Slusher et al. and can be administered to treat diseases or conditions such as cancer and/or those resulting in excess PMSA activity. Koseki et al. uses longer alkyl chains than those that were disclosed as not effective in Slusher et al. and one of ordinary skill in the art would optimize the alkyl chain length in the compounds of formula (I) in Slusher et al. As taught by Koseki et al., the fatty acid chain length affects cytotoxicity, cellular uptake and ester hydrolysis that is critical to the toxicity of the administered agent. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal fatty acid chain length when preparing a compound of formula (I) that can then be administered to a subject to treat a disease such as cancer as taught by Slusher et al. There is no evidence of record that the doses of such a compound used to treat cancer do not fall within the range of an effective amount of shielding agent as required by the instant claims as one of ordinary skill in the art would optimize the dosage of the drug using the considerations discussed by Slusher et al. such as the route of administration, the subject to be treated and the preference and experience of the attending physician. The person of ordinary skill in the art also would have been motivated to use the combination of agents and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Both agents are taught for the treatment of PMSA associated conditions and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer with both agents as in US’457 and Slusher et al. in combination with Koseki et al. since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition. “Selection of any order of process steps is prima facia obvious in the absence of new or unexpected results.” See MPEP § 2144.04, IV. Therefore it would have been obvious to give one drug before the other (sequential administration) or to administer them together in a single combination to minimize the number of administration steps required to deliver both agents to a subject. There is no evidence of record as to new or unexpected results arising from the order of administration of the two different compounds.
As to the location of binding of the shielding agent of the instant claims upon administration, this necessarily flows from the structure of the compound that determines the in vivo binding behavior of each compound when administered. While binding to PSMA expressed on non-cancerous cells such as those of the tissues recited in claims 39 and 49 is not explicitly disclosed by the prior art, that is not required to render the claims obvious as the therapeutic activities of both compounds renders obvious administration of both agents to a subject with cancer such as prostate cancer. The administration of both of the claimed compounds to a subject having cancer that expresses PSMA, the binding target of the compounds being administered for the administered active agents, is rendered obvious. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Therefore the explicit recitation in the claims of a compound such as the shielding agent blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell does not patentably distinguish the instant claims over the applied prior art.
This is a provisional nonstatutory double patenting rejection.
Claims 2, 4 – 6, 38, 39 and 47 – 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of copending Application No. 19/538,457 in view of Slusher et al. (US 2017/0226141) and Koseki et al. (Bull Chem Soc Jpn, 2016) and optionally further in view of Eder et al. (US 201620160228587).
The claims of US’457 recite a method of treating PMSA expressing cancer with a combination therapy of a radiolabeled compound of Formula Ia as in claim 1, a PD-1 inhibitor and a CTLA-4 inhibitor. The radionuclide can be 177Lu (claims 8 and 9).Further anti-cancer agents can also be administered (claim 3). The PMSA expressing cancer can be prostate cancer (claim 5).
Co-administration with a compound such as the shielding agents of instant claim 2 is not claimed.
Slusher et al. and Koseki et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to compound of formula (I) of Slusher et at. with a longer alkyl chain such as C12 which fall within the scope of compounds of formula (I) of Slusher et al. and can aid in the formation of particles of the compound as taught by Koseki et al. which is administered with the therapeutic agents of US’457. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such compounds fall within the scope of formula (I) of Slusher et al. and can be administered to treat diseases or conditions such as cancer and/or those resulting in excess PMSA activity. Koseki et al. uses longer alkyl chains than those that were disclosed as not effective in Slusher et al. and one of ordinary skill in the art would optimize the alkyl chain length in the compounds of formula (I) in Slusher et al. As taught by Koseki et al., the fatty acid chain length affects cytotoxicity, cellular uptake and ester hydrolysis that is critical to the toxicity of the administered agent. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal fatty acid chain length when preparing a compound of formula (I) that can then be administered to a subject to treat a disease such as cancer as taught by Slusher et al. There is no evidence of record that the doses of such a compound used to treat cancer do not fall within the range of an effective amount of shielding agent as required by the instant claims as one of ordinary skill in the art would optimize the dosage of the drug using the considerations discussed by Slusher et al. such as the route of administration, the subject to be treated and the preference and experience of the attending physician. The person of ordinary skill in the art also would have been motivated to use the combination of agents and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. Both agents are taught for the treatment of PMSA associated conditions and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer with both agents as in US’457 and Slusher et al. in combination with Koseki et al. since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition.
The treatment of specific types of prostate cancer is not claimed.
Eder et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject with prostate cancer that such as one with metastatic cancer that has become castration resistant/androgen independent with a radiolabeled compound such as the 177Lu-MB17 of Eber et al. in combination with the optimized compounds of formula (I) of Slusher et al. and Koseki et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because for agents are useful for the treatment of conditions associated with PMSA such as prostate cancer and Eder et al. discloses that PMSA is abundantly expressed on prostate cancer cells at all stages of the disease including the castration resistant form of metastatic prostate cancer. Therefore the person of ordinary skill in the art would have been motivated to treat a subject with prostate cancer such as metastatic castration resistant prostate cancer with both agents since one of ordinary skill in the art would reasonably expect each to be useful for the treatment of the same condition. “Selection of any order of process steps is prima facia obvious in the absence of new or unexpected results.” See MPEP § 2144.04, IV. Therefore it would have been obvious to give one drug before the other (sequential administration) or to administer them together in a single combination to minimize the number of administration steps required to deliver both agents to a subject. There is no evidence of record as to new or unexpected results arising from the order of administration of the two different compounds.
As to the location of binding of the shielding agent of the instant claims upon administration, this necessarily flows from the structure of the compound that determines the in vivo binding behavior of each compound when administered. While binding to PSMA expressed on non-cancerous cells such as those of the tissues recited in claims 39 and 49 is not explicitly disclosed by the prior art, that is not required to render the claims obvious as the therapeutic activities of both compounds renders obvious administration of both agents to a subject with cancer such as prostate cancer. The administration of both of the claimed compounds to a subject having cancer that expresses PSMA, the binding target of the compounds being administered for the administered active agents, is rendered obvious. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Therefore the explicit recitation in the claims of a compound such as the shielding agent blocking the binding of the radiolabeled therapeutic to PSMA expressed on a non-cancerous cell does not patentably distinguish the instant claims over the applied prior art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Nissa M Westerberg/Primary Examiner, Art Unit 1618
Prosecution Insights