DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions and Claim Status
Applicant's election with traverse of Group 2 and the species of compound 45-164 in the reply filed on 6/15/26 is acknowledged. The traversal is on the ground(s) that there is no undue burden to search all claims. This is not found persuasive because burden is not necessarily the standard for this 371 application. Further, Groups 1 and 2 require different structures which would require different searches. A search of a method of making is not the same as a search of a method of administering. With respect to the species, there are many possible species (see claim 1).
The requirement is still deemed proper and is therefore made FINAL.
Claims 3-4 and 9-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/15/26.
Claims to the elected species are rejected as set forth below. Any relevant art uncovered during the search for the elected species is cited herein in order to advance prosecution.
Claims 1-2 and 5-8 are being examined.
Priority
The priority information is found in the filing receipt of 9/14/23. There is no translation of foreign priority documents of record at this time.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/20/23, 9/13/23 and 3/22/23 have been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2 and 5-8 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.
At numerous locations claim 1 recites ‘preferably’ or ‘more preferably’. MPEP 2173.05(d) states that preferences are properly set forth in the specification not the claims and that preferences in the claims can lead to confusion as to whether or not the narrower range is a limitation. Regarding claim 1, the phrases "preferably" or “more preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Dependent claims 5-8 do not clarify the claim scope.
The V variable of claim 1 refers to Y1 and Y0. Although Y1 and Y0 are later defined, it is unclear if they are the same as Y1 and Y0.
Claim 1 recites T and claim 2 recites iRGD-PPT or PPT-iRGD. Page 29 of the specification recites a structure for PPT-iRGD. The first option for T of claim 1 and the structure for PPT-IRGD of claim 2 (as defined on page 29 of the specification) is unclear. The structure is not legible and the bonds and/or stereochemistry are not clear. For example the bond in the proline that is attached to the free cysteine is not clear. While the 2nd structure for T in claim 1 clearly shows dashes at such location, the corresponding location in the first option for T is unclear. It is also unclear at other locations within the first structure for T of claim 1 and PPT-iRGD as defined on page 29 of the specification if any stereochemistry is required. It is not clear if claim 2 is a proper dependent claim. Claim 2 recites ‘the polyethylene glycol conjugated drug is selected from:’ and then presents a table. The first line of the Table recites:
N
o.
It is unclear what such entry means.
At numerous locations claim 7 recites ‘preferably’ or ‘more preferably’. MPEP 2173.05(d) states that preferences are properly set forth in the specification not the claims and that preferences in the claims can lead to confusion as to whether or not the narrower range is a limitation. Regarding claim 7, the phrases "preferably" or “more preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Claim 7 recites that N is G. It is unclear if G is a variable group or Gly or something else.
Claim 8 recites ‘the polyethylene glycol conjugated drug is selected from:’ and then recites one specific compound. When the language ‘is selected from’ is used, there are usually more than one option. It is unclear if claim 8 is drawn to a specific formula or if there are actually other possibilities.
Claim 8 refers to ‘polyethylene glycol conjugated drug’. However, claim 1 recites a polyethylene glycol conjugated drug of formula I while claim 6 refers to a polyethylene glycol conjugated drug of formula A. It is unclear which polyethylene glycol conjugated drug is being referenced.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
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 1-2 and 5-8 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
(1) Scope of the invention/Partial structure/disclosure of drawings:
Claim 1 recites a drug synergist of formula I. Claim 1 does not refer to what drug is being synergized so the scope of possible drugs is immense and could be for treating any range of ailments including viral, bacterial, genetic or neurodegenerative diseases or disorders. As discussed above the claims are unclear. Claims 2 and 5 do not provide any information about the drug. Although certain claims refer to the drug (claim 6) such claims encompass a wide range of possible synergists (see formula I).
The specification (example 2) recites a specific example with a specific compound and drug.
(2) Level of skill and knowledge in the art/predictability in the art:
The level of skill in the art is high.
The specification teach that an internalization RGD polypeptide has tumor targeting abilities (page 2 2nd paragraph).
Claim 1 recites a drug synergist of formula I. Claim 1 does not refer to what drug is being synergized so the scope of possible drugs is immense and could be for treating any range of ailments including viral, bacterial, genetic or neurodegenerative diseases or disorders.
One would not recognize tumor targeting as being an effective drug synergist for drugs that target viral, bacterial, genetic or neurodegenerative diseases or disorders.
(3) Physical and/or chemical properties and (4) Functional characteristics:
Claim 1 and dependent claims require a synergist activity.
The specification teach that an internalization RGD polypeptide has tumor targeting abilities (page 2 2nd paragraph).
There is no specific disclosed correlation between structure and function particularly related to what structures are adequate to result in the functions as recited in the claims particularly for. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus and that there is a lack of the predictability in the art thus that the applicant was not in possession of the claimed genus.
(5) Method of making the claimed invention/actual reduction to practice:
The specification (example 2) describes a specific compound and drug. It is not clear from the data provided that the results are actually synergistic (ss MPEP 716.02a).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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) 1-2 and 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO 2021/104120; 06-2021) in view of Peng et al. (‘Enhancing accumulation and penetration of HPMA copolymer-doxorubicin conjugates in 2D and 3D prostate cancer cells via iRGD conjugation with an MMP-2 cleavable spacer’ JACS v137 2015 pages 6726-6729; ‘Peng’) in view of Cui et al. (WO 2021/158780; 08-2021; ‘Cui’).
Li et al. (WO 2021/104120) is not in the English language. All references herein will be to the English language version US 2023/0088403 (‘Li’).
Li teach polyethylene glycol conjugate medicaments including those of formula I (abstract). Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002). Li teach conjugates with excellent tumor inhibition activity (section 0005). Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Li teach an example of a compound that is named 49-166 (page 718).
Li does not teach the T component of claim 1.
Peng teach the tumor homing and penetrating cyclic peptide iRGD and its use to enhance accumulation and penetration of medicines in tumor tissue (abstract). Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3).
Cui also teach the use of an iRGD segment and MMP-2 responsive substrate to improve treatment efficacy and reduced side effects (section 0069 and claims 14 and 16) and recite PLGLAG-cyl[CRGDRGPDC] (section 0127 for example). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Li because Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002) and teach conjugates with excellent tumor inhibition activity (section 0005). Since Peng and Cui teach components that enhance accumulation and penetration and improve treatment efficacy and reduce side effects specifically for tumor treatment one would have been motivated to use such components based on the advantageous effects. Specifically one would have been motivated to make PLGLAG-cyl[CRGDRGPDC] containing compounds based on the known beneficial effects. Further, based on the specific teachings of Li, one would have been motivated to make compounds and compounds suggested by Li. One would have had a reasonable expectation of success because Li expressly teach a compound and method of synthesis (example 32 sections 0926-0946).
In relation to the conjugate of formula I of claims 1-2, as discussed above the claims are unclear. However, Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Thus, Li suggests compound of formula I as currently interpreted. Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088). Thus, Peng and Cui suggest instant T as currently interpreted.
In relation to the polymer drug of claims 5-8, Li teach an example of a compound that is named 49-166 (page 718) which is recited in claim 8.
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 1-2 and 5-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11793881 in view of Li et al. (WO 2021/104120; 06-2021) in view of Peng et al. (‘Enhancing accumulation and penetration of HPMA copolymer-doxorubicin conjugates in 2D and 3D prostate cancer cells via iRGD conjugation with an MMP-2 cleavable spacer’ JACS v137 2015 pages 6726-6729; ‘Peng’) in view of Cui et al. (WO 2021/158780; 08-2021; ‘Cui’).
11793881 recites polyethylene glycol conjugated drugs of formula I (claim 1) and methods of treating cancer (claim 21). 11793881 recites a specific compound (columns 1565-1566).
11793881 does not recite instant T.
Li et al. (WO 2021/104120) is not in the English language. All references herein will be to the English language version US 2023/0088403 (‘Li’).
Li teach polyethylene glycol conjugate medicaments including those of formula I (abstract). Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002). Li teach conjugates with excellent tumor inhibition activity (section 0005). Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Li teach an example of a compound that is named 49-166 (page 718).
Peng teach the tumor homing and penetrating cyclic peptide iRGD and its use to enhance accumulation and penetration of medicines in tumor tissue (abstract). Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3).
Cui also teach the use of an iRGD segment and MMP-2 responsive substrate to improve treatment efficacy and reduced side effects (section 0069 and claims 14 and 16) and recite PLGLAG-cyl[CRGDRGPDC] (section 0127 for example). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 11793881 because 11793881 teach methods of treating cancer (claim 21) and teach specific compounds (columns 1565-1566). Since Li, Peng and Cui teach either similar conjugates or components that enhance accumulation and penetration and improve treatment efficacy and reduce side effects specifically for tumor treatment one would have been motivated to use such components based on the advantageous effects. Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002) and teach conjugates with excellent tumor inhibition activity (section 0005). Specifically one would have been motivated to make PLGLAG-cyl[CRGDRGPDC] containing compounds based on the known beneficial effects. Further, based on the specific teachings of Li, one would have been motivated to make compounds and compounds suggested by Li. One would have had a reasonable expectation of success because Li expressly teach a compound and method of synthesis (example 32 sections 0926-0946) and 11793881 recites methods of treating cancer (claim 21).
In relation to the conjugate of formula I of claims 1-2, as discussed above the claims are unclear. However, Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Thus, Li suggests compound of formula I as currently interpreted. Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088). Thus, Peng and Cui suggest instant T as currently interpreted.
In relation to the polymer drug of claims 5-8, 11793881 recites a specific compound (columns 1565-1566). Li teach an example of a compound that is named 49-166 (page 718) which is recited in claim 8.
Claims 1-2 and 5-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18561169 (169) in view of Li et al. (WO 2021/104120; 06-2021) in view of Peng et al. (‘Enhancing accumulation and penetration of HPMA copolymer-doxorubicin conjugates in 2D and 3D prostate cancer cells via iRGD conjugation with an MMP-2 cleavable spacer’ JACS v137 2015 pages 6726-6729; ‘Peng’) in view of Cui et al. (WO 2021/158780; 08-2021; ‘Cui’).
This is a provisional nonstatutory double patenting rejection.
169 recites a conjugate of a specific structure (claim 6 beginning in page 27). 169 recites for treating cancer (claim 11).
169 does not recite instant T.
Li et al. (WO 2021/104120) is not in the English language. All references herein will be to the English language version US 2023/0088403 (‘Li’).
Li teach polyethylene glycol conjugate medicaments including those of formula I (abstract). Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002). Li teach conjugates with excellent tumor inhibition activity (section 0005). Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Li teach an example of a compound that is named 49-166 (page 718).
Peng teach the tumor homing and penetrating cyclic peptide iRGD and its use to enhance accumulation and penetration of medicines in tumor tissue (abstract). Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3).
Cui also teach the use of an iRGD segment and MMP-2 responsive substrate to improve treatment efficacy and reduced side effects (section 0069 and claims 14 and 16) and recite PLGLAG-cyl[CRGDRGPDC] (section 0127 for example). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 169 because 169 teach methods of treating cancer (claim 11) and teach specific compounds (claim 6 beginning in page 27). Since Li, Peng and Cui teach either similar conjugates or components that enhance accumulation and penetration and improve treatment efficacy and reduce side effects specifically for tumor treatment one would have been motivated to use such components based on the advantageous effects. Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002) and teach conjugates with excellent tumor inhibition activity (section 0005). Specifically one would have been motivated to make PLGLAG-cyl[CRGDRGPDC] containing compounds based on the known beneficial effects. Further, based on the specific teachings of Li, one would have been motivated to make compounds and compounds suggested by Li. One would have had a reasonable expectation of success because Li expressly teach a compound and method of synthesis (example 32 sections 0926-0946) and 169 recites for treating cancer (claim 11).
In relation to the conjugate of formula I of claims 1-2, as discussed above the claims are unclear. However, Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Thus, Li suggests compound of formula I as currently interpreted. Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088). Thus, Peng and Cui suggest instant T as currently interpreted.
In relation to the polymer drug of claims 5-8, 169 recites a conjugate of a specific structure (claim 6 beginning in page 27). Li teach an example of a compound that is named 49-166 (page 718) which is recited in claim 8.
Claims 1-2 and 5-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18016909 (909) in view of Li et al. (WO 2021/104120; 06-2021) in view of Peng et al. (‘Enhancing accumulation and penetration of HPMA copolymer-doxorubicin conjugates in 2D and 3D prostate cancer cells via iRGD conjugation with an MMP-2 cleavable spacer’ JACS v137 2015 pages 6726-6729; ‘Peng’) in view of Cui et al. (WO 2021/158780; 08-2021; ‘Cui’).
This is a provisional nonstatutory double patenting rejection.
909 recites polyethylene glycol conjugated drugs (claim 1). 909 recites a specific T group (page 7 of 1/5/26 claims). 909 recites for treating cancer (claim 16).
909 does not appear to recite a specific example that reads on the claims.
Li et al. (WO 2021/104120) is not in the English language. All references herein will be to the English language version US 2023/0088403 (‘Li’).
Li teach polyethylene glycol conjugate medicaments including those of formula I (abstract). Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002). Li teach conjugates with excellent tumor inhibition activity (section 0005). Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Li teach an example of a compound that is named 49-166 (page 718).
Peng teach the tumor homing and penetrating cyclic peptide iRGD and its use to enhance accumulation and penetration of medicines in tumor tissue (abstract). Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3).
Cui also teach the use of an iRGD segment and MMP-2 responsive substrate to improve treatment efficacy and reduced side effects (section 0069 and claims 14 and 16) and recite PLGLAG-cyl[CRGDRGPDC] (section 0127 for example). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 9099 because 9099 teach methods of treating cancer (claim 16). Since Li, Peng and Cui teach either similar conjugates or components that enhance accumulation and penetration and improve treatment efficacy and reduce side effects specifically for tumor treatment one would have been motivated to use such components based on the advantageous effects. Li teach polymer-anticancer drugs to protect from degradation and to enhance the half-life and bioavailability of the drug (section 0002) and teach conjugates with excellent tumor inhibition activity (section 0005). Specifically one would have been motivated to make PLGLAG-cyl[CRGDRGPDC] containing compounds based on the known beneficial effects. Further, based on the specific teachings of Li, one would have been motivated to make compounds and compounds suggested by Li. One would have had a reasonable expectation of success because Li expressly teach a compound and method of synthesis (example 32 sections 0926-0946) and 909 recites for treating cancer (claim 16).
In relation to the conjugate of formula I of claims 1-2, as discussed above the claims are unclear. However, Li provides details about the conjugate in the claims and sections 0007-0055. Li recognizes that j2 and j3 can be 0 (section 0026). Li teach that j1 can be 4 (section 0025). Li teach that M can be specific variables including the first compound of the 2nd column of page 2. Li teach that Z1 and Z0 can be specific options (see the 2nd to last option of section 0055). Li teach that W1 can be z1(zo-(q)2)2 (section 0014). Li teach that PEG can have a variety of molecular weights (section 0008). Li recognizes that L1, A2 and Y can be direct bonds (sections 0012-0013 and 0022). Thus, Li suggests compound of formula I as currently interpreted. Peng teach the iRGD sequence as CRGDKGPDC (page 6726 first complete paragraph of column 2). Peng teach that the polymer was conjugated via PLGLAG peptide spacer which is cleaved in the tumor microenvironment (pages 6726-6727 connecting paragraph and figure 3). Cui teach that suitable linkers include disulfide groups and maleimides (section 0088). Thus, Peng and Cui suggest instant T as currently interpreted.
In relation to the polymer drug of claims 5-8, Li teach an example of a compound that is named 49-166 (page 718) which is recited in claim 8.
Conclusion
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
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