*DETAILAED ACTION*
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a continuation of 16/498,595 filed on 09/27/2019, which is a 371 of PCT/US18/25059 filed on 03/29/2018, which claims benefit in provisional application 62/478,457 filed on 03/29/2017 and in provisional application 62/513,248 filed on 05/31/2017.
Claim Status
Claims 76-95 are pending and examined. Claims 1-75 were canceled.
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 76-95 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.
Claim 76 recites the limitation "the reversible thermal gel polymer" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim. The claim provides support for “the reversible thermal gel polymers”.
Claim 76 recites the limitation "the subject" in the last line of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 84 recites “aneurysm-related condition or process”. The claim is indefinite because the scope of the conditions and processes encompassed by the phrase is unknown. The specification was reviewed and it does not mention the phrase nor provide any clarification about its meaning.
Claim 94 recites the limitation "the target medium" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 77-83, 85-93, and 95 are indefinite because the claims depend from an indefinite base claim.
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.
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.
Claims 76, 78, 83, and 94 are rejected under 35 U.S.C. 103 as being unpatentable over Park (WO 2015/106149 A2 Published July 16, 2015 – of record in IDS dated 04/05/2024).
The claims encompass a method of using reversible thermal gel polymers.
The teachings of Park are related to polymers having reverse thermal gelling properties and transform from liquid to a gel near or below body temperature, such as a skin temperature in an operating room. The polymers can be applied to a surface, such as a surface of skin proximate an incision site prior to surgery, to provide a relatively sterile area near the site (Abstract). The polymer is a block copolymer comprising a reverse thermal gel block (a PSHU-PNIPAAm block) and an antimicrobial functional group block comprising quaternized amine group (page 2 lines 5-13). The polymer structure is shown in line 20 on page 3. In an exemplary embodiment, an antimicrobial reverse thermal gel composition includes a copolymer comprising an antimicrobial functional group block and a reverse thermal gel block or portion. The composition can comprise, consist essentially of, or consist of the copolymer and a carrier, which can consist of, consist essentially of, or comprise a diluent, e.g., water or ethanol. The composition can include, for example, about 2 wt. % to about 20 wt. % polymer in solution (page 4 lines 1-8).
Regarding claim 76, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed a composition comprising 2-20 wt. % of a polymer having a thermosensitive block PNIPAAm-NH-PSHU and an antimicrobial block Q-PSHU and utilized the composition in a method of mitigating the risk of infection to the patient comprising applying the composition to the skin of the patient prior to surgery, with a reasonable expectation of success because Park teaches a composition comprising 2-20 wt. % of polymers having a thermosensitive block PNIPAAm-NH-PSHU and an antimicrobial block Q-PSHU wherein the composition is useful for applying to a surface of skin proximate an incision site prior to surgery, to provide a relatively sterile area near the site mitigating the risk of infection (page 5 lines 17-25). It would have been obvious to have formed the composition to have a viscosity of less than 50 cP before transition to a gel because Park teaches that the composition has a viscosity below 50 cP before transition to a gel (page 10 lines 8-12). The claimed polymer is obvious because Park’s polymer comprises a block Q-PSHU, which meets the limitation of a first block comprising first repeating units wherein each repeating unit independently comprises a hydrophilic group. Quaternized amine group is hydrophilic. Park’s polymer comprises PNIPAAm-NH-PSHU which meets the limitation of a second polymer block comprising second repeating units wherein each second repeating unit independently comprises a thermosensitive group. PNIPAAm is a thermosensitive group.
The claimed concentration range is obvious because it overlaps with Park’s concentration range of 2-20 wt. %.
The claimed viscosity range is obvious because it is encompassed by Park’s viscosity range of 50 cP and less.
Regarding claim 78, providing sterility and mitigating the risk of infection is considered a therapeutic process.
Regarding claim 83, it would have been obvious to have stored the composition at a temperature below 30°C prior to use because Park teaches that the formulation has a viscosity of
less than 50 cP at a temperature of 30°C or less or below a skin temperature prior to or during surgery. The purpose of the composition is to gel at the surgical site, therefore it would have been obvious to use the composition in liquid form and the skilled artisan would have recognized that the composition would have to be stored at a temperature below skin temperature such as less than 30°C in order to be usable for its intended purpose. The claimed temperature range is obvious because it encompasses less than 30°C.
Regarding claim 94, Park’s polymer comprise antimicrobial quaternized amine groups, therefore Park’s method delivers a drug to the skin where surgical incision is made.
Claims 76-78, 83, 94, and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng (US 2005/0020719 A1 Published January 27, 2005).
The claims encompass a method of using reversible thermal gel polymers.
The teachings of Cheng are related to gellable copolymer compositions comprising a copolymer in a solvent. The copolymer has an architecture A(B)n where n is greater than 1. The composition forms a gel under environmental conditions in which B is insoluble through formation of B aggregates. Block copolymers comprising polyethylene glycol (PEG) and poly(N-iso-propylacrylamide) (PNIPAAm) having a liquid form at ambient temperature under aqueous conditions and a gel form at body temperature are disclosed (Abstract). The composition contains the polymer and a solvent where the polymer is present in a concentration range of 10-25% by weight (paragraph 0063). For compositions having an LCST between ambient temperature and body temperature, the environmental condition that triggers gel formation is beating to body temperature. Thus, inserting the composition into the body causes the biologically active molecule to be trapped in the gel at the site of application, and sustained release from the site would then result (paragraph 0067). The composition may be injected into a blood vessel to block blood flow in that vessel. Such an application may be useful upstream of a tumor to block blood flow to the tumor. It may also be used as a temporary sealant during surgery (paragraph 0071). Example 9 teaches a composition formed using polymers having AB and AB4architecture. The composition comprises a total of 15 wt. % copolymer in physiological saline. The proportion of AB to AB4 is 2:3. The resulting composition is liquid at ambient temperature, and converts to a gel when injected into a subcutaneous site of a subject. This change is due to the change from ambient temperature to body temperature (Paragraph 0130).
Regarding claim 76, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have practiced a method of blocking blood flow to a tumor by injecting a composition into a blood vessel block blood flow, with a reasonable expectation of success because Cheng teaches blocking blood flow to a tumor by injecting a composition into a blood vessel to block blood flow in that vessel. It would have been obvious to have used a composition polymers having AB and AB4architecture where A is polyethylene glycol and B is poly(N-isopropylacrylamide), wherein the composition contains a total of 15 wt. % copolymer in physiological saline and wherein the proportion of AB to AB4 is 2:3, with a reasonable expectation of success because Cheng teaches such composition in example 9 and teaches that the composition is liquid at ambient temperature and changes to a gel when injected subcutaneously and that the change is caused by the change in temperature.
The claimed polymer is obvious over a AB or AB4 bock copolymer contains a PEG block and a PNIPAAm block, where the PEG block meets the limitations of a first polymer block because it contains repeating units that comprise a hydrophilic group. The PNIPAAm block meets the limitations of the second polymer block because it contains repeating units comprising a thermosensitive group and the two blocks are covalently bonded.
The claimed concentration range of polymer in the composition is obvious because 15 wt. % is encompassed by the claimed range. The copolymer AB is present at concentration of 6 wt. % and the copolymer AB4 is present at a concentration of 9 wt. %.
It would have been obvious to have formulated the composition to have a viscosity of 750 cP, 950 cP, 900 cP, or 700 cP because Cheng teaches that these viscosities are low enough to easily inject the composition through a 25 G needle (paragraph 0118). The claimed viscosity range is obvious because it encompasses Cheng’s values.
Regarding claims 77 and 95, the claimed polymers FX1 and FX3 are obvious over Cheng’s AB copolymer PEG-PNIPAAm. Example 9 teaches that copolymers were made according to example 4. Table 3 in example 4 describes copolymer AB the A block has a molecular weight of 2000 Da and the B block has a molecular weight of 1900-2300 Da (Table 3 in paragraph 0097).
A PEG block having a molecular weight of 2000 Da contains about 45 repeating units of ethyleneoxide. A PNIPAAm block having a molecular weight range of 1900-2300 Da contains from about 16 to about 20 repeating units derived from N-ispropylacrylamide.
Cheng’s AB copolymer is encompassed by claimed polymer of formula FX1 when
B1 is as shown in the claim,
B2 is as shown in the claim,
Y is -OH,
L1 and L2 are both CqH2q-1 where q is 2;
L3 is absent and c is 0,
W1 is absent and a is 0,
W2 is absent and b is 0,
z is 1,
m is 16-20,
n is 45,
p is 1, and
R1, R2, R3, and R4 are all hydrogen.
Claimed formula FX3 encompasses Cheng’s formula AB when
Y is -OH,
L3 is absent and c is 0,
W1 is absent and a is 0,
W2 is absent and b is 0,
R1, R2, R3, and R4 are all hydrogen atoms,
n is about 45,
z is 1,
m is about 16-20, and
p is 1.
Regarding claim 78, blocking blood flow to a tumor is considered a therapeutic process.
Regrading claim 83, Cheng teaches that the composition is a liquid at ambient temperature and it is required to be liquid prior to administration and it converts to a gel once administered subcutaneously, therefore it would have been obvious to have stored the composition at an ambient temperature that is below human body temperature. The claimed temperature range is obvious because temperature below human body temperature overlaps with the claimed temperature range.
Regarding claim 94, it would have been obvious to have formulated the composition with a drug and utilized the composition as a drug delivery system because Cheng teaches that the composition may be formulated with a drug (paragraph 0059) and that the formulation may be used as a drug delivery system (paragraph 0065).
Claims 79-82, 84, 85, and 89-93 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng as applied to claims 76-78, 83, 94, and 95 above, and further in view of Schwarz (US 2005/0008610 A1 Published January 13, 2005).
The claims encompass a method of using reversible thermal gel polymers.
The teachings of Cheng are relied upon as summarized above. They do not teach the limitations of claims 79-82 and 84-93.
The teachings of Schwarz are related to methods of embolizing a vascular site in a mammal comprising introducing into the vasculature of a mammal a composition comprising an inverse thermosensitive polymer, wherein said inverse thermosensitive polymer gels in said vasculature, which composition is injected through a small catheter, and which composition gels at or below body temperature. In some embodiments the composition further comprises a marker molecule such as radiopaque or an MRI-visible compound (Abstract and paragraph 0016). The transition temperature of the polymer is between 10°C and 40°C (paragraph 0018). The polymer is a thermosensitive block copolymer (paragraph 0021). Embolization is a process wherein a material is injected into a blood vessel to at least partially fill or plug the vessel and/or encourage clot formation so that blood flow through the vessel is reduced or stopped. Embolization of a blood vessel can be useful for a variety of medical reasons, including preventing or controlling bleeding due to lesions (e.g., organ bleeding, gastrointestinal bleeding, vascular bleeding, and bleeding associated with an aneurysm), or to ablate diseased tissue (e.g., tumors, vascular malformations, hemorragic processes) by cutting off blood supply. Embolization may also be used to prevent blood loss during or immediately following surgery. Embolization of tumors may be performed preoperatively to shrink tumor size; to aid in the visualization of a tumor; and to minimize or prevent blood loss related to surgical procedures (paragraph 0082).
The teachings of Cheng and Schwarz are related to compositions intended for embolization of blood vessels for the purpose of stopping blood flow and methods of using said compositions, and it would have been obvious to have combined their teachings because they are in the same field of endeavor.
Regarding claims 79 and 80, it would have been prima facie obvious a person of ordinary skill in the art before the effective filing date of the claimed invention to have practiced Cheng’s method using a microcatheter with a reasonable expectation of success because Schwarz teaches that a microcatheter is a suitable device for administering a liquid composition to a blood vessel wherein the composition is intended embolize the blood vessel (paragraphs 0083, 0086, 0087, 0096).
Regarding claim 81, Schwarz teaches that injections led to a consistent vascular occlusion at any site, provided the agent could be injected at a sufficient rate to fill the vascular lumen and gel before being carried away by blood flow (paragraph 0060). It would have been obvious to have injected Cheng’s formulation via a microcatheter to a blood vessel at a rate that results in successful embolization of the blood vessel because the purpose the Cheng is to stop blood flow in a blood vessel. The skilled artisan would have arrived at a range of flow rates that successfully accomplish the purpose of the method and the range would have overlapped with the claimed range or it would have been close enough to the claimed range that the skilled artisan would have expected the flow rates to have the same effect. The specification was reviewed and there is no evidence that the claimed flow rate is critical.
Regarding claim 82, Cheng teaches that composition transitions from liquid prior to injection to a gel once injected into the subject.
Regarding claims 84 and 85, it would have been obvious to have administered a polymer composition to a subject wherein the composition is intended for embolizing a blood vessel in order to prevent or control bleeding due to an aneurysm, with a reasonable expectation of success because Schwarz teaches that a polymer composition that gels at body temperature is useful for embolization of blood vessels and teaches that such compositions are suitable for preventing or controlling bleeding associated with an aneurysm (paragraph 0082). It would have been obvious to have practiced Schwarz’ method with Cheng’s polymer formulation because Cheng’s polymer formulation transitions from liquid at ambient temperature to gel at body temperature and Cheng teaches that the polymer composition is suitable for stopping blood flow in a blood vessel. The selection of a known material or a method suitable for its intended purpose supports obviousness.
Regarding claim 89, it would have been obvious to have formed Cheng’s polymer composition with a radiopaque compound with a reasonable expectation of success because Schwarz teaches forming polymer compositions intended for embolization with a radiopaque compounds in order to be able to detect and tack the embolus (paragraphs 0088, 0089, 0091, and 0094). Combining prior art elements according to known methods to obtain predictable results supports obviousness.
Regarding claims 90 and 91, it would have been obvious to have imaged the blood vessel where the embolus was formed using MRI because imaging an embolus using MRI was known from Schwarz (paragraph 0091).
Regarding claim 92, the skilled artisan would have expected to localize the site where the embolus was formed, which is the target medium, after injecting a polymer composition comprising a radiopaque compound and imaging the site. Schwarz teaches that the purpose of radiopaque compound is to be able to detect and track the embolus.
Regarding claim 93, It would have been obvious to have administered the polymer composition comprising radiopaque compound to an aneurysm and subsequently imaged the embolus in order to track and monitor it, with a reasonable expectation of success because Schwarz teaches that the polymer compositions comprising a radiopaque compound are suitable for preventing or controlling bleeding associated with an aneurysm and teaches using imaging such as MRI to monitor and tack the embolus.
Claims 86-88 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng and Schwarz as applied to claims 76-85 and 89-95 above, and further in view of Chobotov (US 2005/0090804 A1 Published April 28, 2005).
The teachings of Cheng and Schwartz are relied upon as summarized above. They do not teach the limitations of claims 86-88.
The teachings of Chobotov are related to methods and compositions for managing endoleaks in a perigraft space around an endovascular graft (Abstract). Access to the perigraft space for injection of the embolic material may be achieved translumbar (paragraph 0014). For embolic materials with a longer cure time, the embolic material may be injected into the perigraft space in a less precise or specific locations, and the embolic material may be allowed to penetrate into the branch vessels for sealing of Type II endoleaks, so as to embolize and close off the leak paths. Depending on the characteristics of the embolic material, if a blood flow through the perigraft space and endovascular graft is not stopped or substantially reduced, the embolic material may perfuse from the perigraft space prior to curing and sealing of the endoleaks and may create potential embolic complications in the bowels or peripheral circulation (paragraph 0055). Useful embolic materials generally include those formed by the mixing of multiple components and that have a cure time ranging from a few minutes or less to tens of minutes, preferably from about one to about ten minutes such that the embolic material is allowed to penetrate into the targeted branch vessels and/or penetrate into the endoleak, but not beyond. For instance, such a material should have a relatively low viscosity before solidification or curing to facilitate the process of filling the desired volume. The embolic material may be radiopaque, both acutely and chronically, although this is not necessary (paragraph 0057).
The teachings of Chobotov, Cheng, and Schwarz are related to methods and compositions for embolizing blood vessels and it would have been obvious to have combined them because they are in the same field of endeavor.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used Cheng’s polymer composition in a method of treating a Type II endoleak by administering the polymer composition in a translumbar manner, with a reasonable expectation of success because it was known from Chobotov that embolization materials that cure in less than 10 minutes are suitable for treating a Type II endoleak by injecting the embolization material into the perigraft space in a translumbar manner. One of skill in the art would have had a reasonable expectation of success using Cheng’s composition because Cheng teaches that the composition cures into a solid white gel within two minutes (paragraph 0089). Combining prior art elements according to known methods to obtain predictable results supports obviousness.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617
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