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 .
DETAILED ACTION
Claims 1, 11, 17 – 18, 20 – 23, 39 – 40, 42 – 44, 53 – 55, 57 – 58, and 73 are pending in this application. Applicant’s amendment, submitted January 31, 2024, is entered, wherein claims 1, 11, 17 – 18, 20 – 23, 39, 40, 44, 53 – 55, 57 – 58, and 73 are amended and claims 2 – 10, 12 – 16, 19, 24 – 38, 41, 45 – 52, 56, 59 – 72, and 74 – 90 are canceled.
Priority
This application is a national stage application of PCT/US2021/038157, filed June 19, 2021, which claims benefit of domestic applications 63/041,678, 63/041,581, and 63/041,616, filed June 19, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/05/2024, 09/19/2024, 12/17/2024, 03/14/2025, and 06/02/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in line 24 of page 189 and line 5 of page 190. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1 and 53 are objected to because of the following informalities:
Claim 1, line 5, “and/or”
Claim 1, line 12, “as cross-linker” should read “, as a cross-linker,”.
Claim 53, line 2, “a tissue” should read “the tissue”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 44, 53 – 55, 57 – 58, and 73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a tissue defect in a subject, does not reasonably provide enablement for preventing a tissue defect, which is caused by a cancer, such as breast cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Claims 53 – 55, 57 – 58, and 73 depend from claim 44.
Applicant claims a method of preventing a condition, which is soft tissue defect that may be caused by cancer, such as breast cancer, in a subject recited in claims 44, 53 – 55, 57 – 58, and 73. However, no limiting definition of “preventing” is given in the instant specification. In the absence of a limiting definition by Applicant, “prevention” as described according to the Glossary of Medical Education Terms (Institute for International Medical Education, page 15 – 16), is a preventive measure, such as preserving physical fitness in primary prevention. Thus, the claimed method of preventing a cancer in a subject as interpreted by a skilled practitioner of the medical or pharmaceutical arts would be to reduce for long-term the occurrence of or to eliminate cancer in a subject by the method. Thus, the claimed method of preventing a cancer comprising administering to the subject a composition of claim 1 as interpreted by a skilled practitioner of the medical or pharmaceutical arts would be to prevent cancer from ever-occurring in a subject by the method.
The Applicant’s attention is drawn to re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider where assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention;
(2) the state of the prior art;
(3) the relative skill of those in the art;
(4) the predictability or unpredictability of the art;
(5) the breadth of the claims;
(6) the amount of direction or guidance presented;
(7) the presence or absence of working examples; and
(8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
(1) Nature of the invention
The rejected invention is drawn to a method of treatment and prevention of a disease, such as breast cancer, in a subject, wherein the method comprising administering to the subject a composition of claim 1. The scope of the claims covers a wide range of cancer across multiple species.
(2) & (4) State of the prior art and predictability or unpredictability of the art
There is no teaching or suggestion in the state of the prior art that application of the composition of claim 1 can prevent a cancer in a subject. Altman et al. (WO2019/005848A1) teach a biocompatible tissue filler comprising the claimed components (page 6, lines 13 – 22) that may be used with another active agent, such as a drug (page 148, lines 2 – 3). Nguyen et al. (Polymers, 2019, Vol. 11, Issue 12, Reference included with PTO-892) teach a DOX-loaded SF-based nanoparticles with magnetic tumor targeting ability. The efficacy of such medication has a survival rate up to 100% within 30 days (page 11, para. 1). Moreover, the specification does not provide adequate examples or sufficient data to show that the claimed composition is effective in preventing a cancer. Therefore, it is unpredictable whether the composition could be effective in preventing a cancer.
(3) Relative skill of those in the art
The relative skill of those in the art is from the pharmaceutical field.
(5) Breadth of claims
The claims are extremely broad in that they encompass the preventing a cancer in a subject using the claimed method.
(6) & (7) Amount of direction or guidance presented and presence or absence of working examples
It is worth to note again that there are no working examples in the instant application to show that the claimed method is effective for preventing a disease, such as breast cancer, as recited in the claims. The exemplary embodiments of the specification merely present the methods of making as well as the mechanical properties of the composition. These examples do not provide any evidence supporting the preventing a cancer through the use of composition.
(8) Quantity of experimentation necessary
In order to practice the full scope of the invention, one skilled in the art would need to undertake a novel and extensive research program to show that a preventive measure can be achieved after applying the claimed method. Furthermore, one of ordinary skill in the art would need to test a representative number of animals toward various cancer before one of ordinary skill in the art would be able to conclude that any method can be used to prevent a cancer in a subject. Because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of use in preventing a cancer in a subject, it would constitute an undue and unpredictable experimental burden.
Genentech, 108F. 3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, applicant fails to provide information sufficient to practice the claimed invention.
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, 11, 17 – 18, 20 – 23, 39 – 40, 42 – 44, 53 – 55, 57 – 58, and 73 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 1 recites “crosslinked by one or more linker moieties comprising one or more of polyethylene glycol (PEG), polypropylene glycol (PPG), and a secondary alcohol” in lines 4 – 6. The phrase renders the scope of the claims unclear. Specifically, it is ambiguous whether the claim requires at least one of the three listed components (PEG, PPG, and/or a secondary alcohol), or at least one component plus a mandatory inclusion of a secondary alcohol due to the use of “and” following “one or more of”. The use of “and” in the final element of a “one or more of” list introduces uncertainty regarding whether the PPG and secondary alcohol are required or optional, thereby failing to inform a person of ordinary skill in the art, with reasonable certainty, as to the scope of the claimed invention. Claims 11, 17 – 18, 20 – 23, 39 – 40, 42 – 44, 53 – 55, 57 – 58, and 73 depends from claim 1 are also indefinite.
Claim Interpretation
The phrase “crosslinked by one or more linker moieties comprising one or more of polyethylene glycol (PEG), polypropylene glycol (PPG), and a secondary alcohol” in lines 4 – 6 of claim 1 will be interpreted as “linker moieties” require any one or any combination of the components from the list.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 11, 18, 20 – 23, 44, 53 – 55, and 57 – 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Altman et al. (WO2019/005848A1, published on January 3, 2019).
Independent claim 1 is directed to a biocompatible composition comprising silk fibroin or silk fibroin fragments, hyaluronic acid (HA), and polyethylene glycol (PEG) and/or polypropylene glycol (PPG), wherein a portion of the HA is modified or crosslinked by one or more linker moieties comprising one or more PEG and a secondary alcohol, wherein a portion of the silk fibroin are crosslinked, wherein the silk fibroin have a polydispersity of between 1 and about 5.0, and wherein the cross-linking is obtained using a polyglycidyl-PEG. Dependent claim 11 is directed to the composition, wherein the composition further comprising lidocaine. Dependent claim 18 is directed to the composition, wherein the composition is injectable through 30G or 27G needles, and having an injection force through a 30G needle between about 1 N and about 100 N. Dependent claims 20 – 21 are directed to the composition, wherein the storage modulus (G’) and loss modulus (G”) of the composition are from about 5 Pa to about 500 Pa. Dependent claim 22 is directed to the composition, wherein the Tan(δ) (G”/G’) of the composition is between 0 to about 1.2. Dependent claim 23 is directed to the composition, wherein the complex viscosity is between 0 to about 25 Pa∙s. Independent claim 44 is directed to a method of treatment of a disease in a subject in need thereof, wherein the method comprising administering to the subject a composition of claim 1, wherein the composition is injected into a tissue or into a space or virtual space between a first tissue and a second tissue. Dependent claims 53 – 54 are directed to the method, wherein the composition is administered into a wall of the tissue and a wall of an internal organ. Dependent claim 55 is directed to the method, wherein the administration of the composition causes bulking of the tissue, and wherein the disease is treated by the bulking of the tissue. Dependent claims 57 – 58 are directed to the method, wherein the disease is gastroesophageal reflux disease (GERD).
Altman et al. teach a HA and silk protein fragments based tissue fillers and methods of the same (Abstract). In one embodiment, the invention is a biocompatible tissue filler comprising a glycosaminoglycan, wherein the glycosaminoglycan is HA, wherein a portion of the HA is cross-linked by cross-linking moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the cross-linked HA comprises a cross-linking moiety comprising a PEG chain (page 3, lines 13 – 14) or a PPG (page 3, line 28). The tissue filler comprising silk protein or silk protein fragments (SPF), wherein the silk protein is silk fibroin, wherein a portion of the SPF are cross-linked (page 8, lines 8 – 17), wherein the cross-linking is obtained using a cross-linking agent that is polyglycidyl-PEG (page 8, lines 24 – 27). In some embodiments, the SPF have a polydispersity of between about 1.5 and about 3.0 (page 7, lines 1 – 2). Altman et al. also disclose that the concentration, size and polydispersity of SPF in the solution may further be altered depending upon the desired use and performance requirements (page 67, lines 30 – 31; page 68, line 1). In one embodiment, the biocompatible tissue filler further includes an active agent, wherein the active agent is an anesthetic agent, wherein the anesthetic agent is lidocaine (page 15, lines 17 – 23). In some embodiments, the fillers have an injection force of about 5 N to about 25 N, wherein the injection form relates to injection through a 30 G needle (page 55, lines 6 – 10). The tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (page 10, line 24) and loss modulus (G”) from about 5 Pa to about 200 Pa (page 173, lines 9 – 10). The tissue filler also has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (page 11, line 14). The tissue fillers described may be provided in methods of treating one or more conditions in a patient in need thereof (page 183, lines 7 – 8). The condition treated by tissue fillers may include a soft tissue condition (page 183, lines 15 – 16). It may be delivered to soft tissue, such as fibrous tissues, muscles, tendons, subcutaneous tissues, and skin (page 184, lines 11 – 14), or void spaces (page 196, lines 26 – 27). One specific condition is gastroesophageal reflux disease (GERD) (page 184, line 10).
For the value of Tan(δ) (G”/G’), (G”/G’) is calculated to be 0.4 if G” is 200 and G’ is 500, which both within the range that disclosed by Altman et al. As the patient population and composition are the same, the composition will also achieve “bulking the tissue” after administration, which addresses claim 55.
For these reasons above, Altman et al. anticipate 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 1, 11, 17 – 18, 20 – 23, 39 – 40, 42 – 44, 53 – 55, 57 – 58, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Altman et al. (WO2019/005848A1, published on January 3, 2019) in view of Nguyen et al. (Polymers, 2019, Vol. 11, Issue 12, Reference included with PTO-892). Claims 1, 11, 18, 20 – 23, 44, 53 – 55, and 57 – 58 are rejected here because they have been rejected by the primary reference under 102.
Regarding 1, 11, 17 – 18, 20 – 23, 39 – 40, 42 – 44, 53 – 55, 57 – 58, and 73, Altman et al. teach a HA and silk protein fragments based tissue fillers and methods of the same (Abstract). In one embodiment, the invention is a biocompatible tissue filler comprising a glycosaminoglycan, wherein the glycosaminoglycan is HA, wherein a portion of the HA is cross-linked by cross-linking moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the cross-linked HA comprises a cross-linking moiety comprising a PEG chain (page 3, lines 13 – 14) or a PPG (page 3, line 28). The tissue filler comprising silk protein or silk protein fragments (SPF), wherein the silk protein is silk fibroin, wherein a portion of the SPF are cross-linked (page 8, lines 8 – 17), wherein the cross-linking is obtained using a cross-linking agent that is polyglycidyl-PEG (page 8, lines 24 – 27). In some embodiments, the SPF have a polydispersity of between about 1.5 and about 3.0 (page 7, lines 1 – 2). Altman et al. also disclose that the concentration, size and polydispersity of SPF in the solution may further be altered depending upon the desired use and performance requirements (page 67, lines 30 – 31; page 68, line 1). In one embodiment, the biocompatible tissue filler further includes one or more active agents (page 148, line 3), wherein the active agent is an anesthetic agent, wherein the anesthetic agent is lidocaine (page 15, lines 17 – 23). In some embodiments, the fillers have an injection force of about 5 N to about 25 N, wherein the injection form relates to injection through a 30 G needle (page 55, lines 6 – 10). The tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (page 10, line 24) and loss modulus (G”) from about 5 Pa to about 200 Pa (page 173, lines 9 – 10). The tissue filler also has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (page 11, line 14). The tissue fillers described may be provided in methods of treating one or more conditions in a patient in need thereof (page 183, lines 7 – 8). The condition treated by tissue fillers may include a soft tissue condition (page 183, lines 15 – 16). It may be delivered to soft tissue, such as fibrous tissues, muscles, tendons, subcutaneous tissues, and skin (page 184, lines 11 – 14), or void spaces (page 196, lines 26 – 27). One specific condition is gastroesophageal reflux disease (GERD) (page 184, line 10).
However, Altman et al. do not teach that the composition further comprises an imaging agent, wherein the imaging agent is a superparamagnetic imaging agent, wherein the superparamagnetic imaging agent is a NP-based magnetic resonance imaging (MRI) contrast agent. Altman et al. also do not teach that the composition further comprises an anticancer treatment for breast cancer, wherein the anticancer treatment is a drug treatment.
Nguyen et al. discloses silk fibroin-based biomaterials for biomedical application (Title). In one study, DOX-loaded SF-based nanoparticles with magnetic tumor targeting ability is prepared. This one-pot salting out technique is used to prepare the combined SF and superparamagnetic Fe3O4 nanoparticle system. The delivery of DOX is performed using external magnetic guidance, and thus, good antitumor efficacy is achieved against multidrug-resistant MCF-7/ADR tumors with survival rate up to 100% within 30 days (page 11, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the biocompatible tissue filler of Altman et al., which further comprising one or more active agents, by incorporating a DOX-loaded SF-based nanoparticle system with superparamagnetic Fe3O4 in view of Nguyen et al. because Altman et al. disclose a drug delivery method using the biocompatible tissue filler, whereas Nguyen et al. suggest an enhanced delivery method using a similar composition. Nguyen et al. explicitly disclose the use of DOX-loaded SF-based nanoparticles including magnetic tumor targeting and demonstrate enhanced antitumor efficacy against multidrug-resistant cancer cells. A person of ordinary skill in the art would have been motivated to apply this known SF-based drug delivery system to the composition of Altman et al. to enhance targeted delivery and therapeutic efficacy of the anticancer agent (DOX). The use of external magnetic guidance for spatially controlled delivery, as shown in Nguyen et al., in combination with the composition of Altman et al. will yield predictable results. For the median particle size of the free SPF, one would have performed routine experimentation to discover the best size of the SPF for the optimal treatment characteristics. For the value of Tan(δ) (G”/G’), (G”/G’) is calculated to be 0.4 if G” is 200 and G’ is 500, which both within the range that disclosed by Altman et al. As the patient population and composition are the same, the composition will also achieve “bulking the tissue” after administration, which reads on claim 55. Furthermore, one of the ordinary skill in the art would have had a reasonable expectation of success because both references relate to biocompatible, injectable silk fibroin systems used in biomedical applications, and the combination does not require fundamentally altering the base system but rather adapting a known drug delivery enhancement of an existing carrier.
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, 11, 18, 20 – 23, 44, 53, 55, and 57 – 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97 – 115 of copending Application No. 18/306,965 in view of Altman et al. (WO2019/005848A1, published on January 3, 2019).
Regarding claims 1, 11, 18, 20 – 23, 44, 53, 55, and 57 – 58, ‘965 teaches a biocompatible tissue filler, comprising HA and SPF having a polydispersity of between 1 and about 5.0, wherein a portion of the HA or SPF is cross-linked by one or more linker moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, and wherein the tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (claim 97). The tissue filler further comprising an anesthetic agent, wherein the anesthetic agent is lidocaine (claims 98 and 100). The tissue filler is injectable (claim 104). The tissue filler has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (claim 111). ‘965 also teaches a method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the tissue filler, wherein the tissue filler is administered to a dermal region of the subject (claims 114 – 115).
However, ‘965 does not teach linker moiety comprising a PEG and the modification is obtained using polyglycidyl-PEG. ‘965 does not teach the loss modulus as well as the complex viscosity. ‘965 also does not teach the tissue comprises a portion of a wall of an internal organ and the condition is GERD.
Altman et al. teach a HA and silk protein fragments based tissue fillers and methods of the same (Abstract). In one embodiment, the invention is a biocompatible tissue filler comprising a glycosaminoglycan, wherein the glycosaminoglycan is HA, wherein a portion of the HA is cross-linked by cross-linking moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the cross-linked HA comprises a cross-linking moiety comprising a PEG chain (page 3, lines 13 – 14) or a PPG (page 3, line 28). The tissue filler comprising silk protein or silk protein fragments (SPF), wherein the silk protein is silk fibroin, wherein a portion of the SPF are cross-linked (page 8, lines 8 – 17), wherein the cross-linking is obtained using a cross-linking agent that is polyglycidyl-PEG (page 8, lines 24 – 27). In some embodiments, the SPF have a polydispersity of between about 1.5 and about 3.0 (page 7, lines 1 – 2). Altman et al. also disclose that the concentration, size and polydispersity of SPF in the solution may further be altered depending upon the desired use and performance requirements (page 67, lines 30 – 31; page 68, line 1). In one embodiment, the biocompatible tissue filler further includes one or more active agents (page 148, line 3), wherein the active agent is an anesthetic agent, wherein the anesthetic agent is lidocaine (page 15, lines 17 – 23). In some embodiments, the fillers have an injection force of about 5 N to about 25 N, wherein the injection form relates to injection through a 30 G needle (page 55, lines 6 – 10). The tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (page 10, line 24) and loss modulus (G”) from about 5 Pa to about 200 Pa (page 173, lines 9 – 10). The tissue filler also has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (page 11, line 14). The tissue fillers described may be provided in methods of treating one or more conditions in a patient in need thereof (page 183, lines 7 – 8). The condition treated by tissue fillers may include a soft tissue condition (page 183, lines 15 – 16). It may be delivered to soft tissue, such as fibrous tissues, muscles, tendons, subcutaneous tissues, and skin (page 184, lines 11 – 14), or void spaces (page 196, lines 26 – 27). One specific condition is gastroesophageal reflux disease (GERD) (page 184, line 10).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the ether group used during the cross-linking as taught by ‘965 with PEG in view of Altman et al. because Altman et al. teach the examples of using PEG or polyglycidyl-PEG as a cross-linker for the production of a biocompatible tissue filler comprising HA and SPF, thereby yielding predictable results. One would have been motivated to incorporate and adjust the rheological properties based on the disclosure of Altman et al. because the incorporation will yield predictable results. As Altman et al. teach other possible uses of the biocompatible tissue filler, one would also have been motivated to apply the similar biocompatible tissue filler to treatment GERD. For the median particle size of the free SPF, one would have performed routine experimentation to discover the best size of the SPF for the optimal treatment characteristics. For the value of Tan(δ) (G”/G’), (G”/G’) is calculated to be 0.4 if G” is 200 and G’ is 500, which both within the range that disclosed by Altman et al. As the patient population and composition are the same, the composition will also achieve “bulking the tissue” after administration, which reads on claim 55. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to substitute the ether group used during the cross-linking as taught by ‘965 with PEG in view of Altman et al. because Altman et al. teach that PEG has been used successfully as a cross-linker in the production of biocompatible tissue filler comprising HA and SPF.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 17 – 18, 20 – 23, 44, 53 – 55, and 57 – 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 87, 89, 93 – 95, 97 – 98, and 100 – 110 of copending Application No. 16/626,081 in view of Altman et al. (WO2019/005848A1, published on January 3, 2019).
Regarding claims 1, 17 – 18, 20 – 23, 44, 53 – 55, and 57 – 58, ‘081 teaches a method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a biocompatible tissue filler, comprising HA, an anesthetic agent, and SPF, wherein a portion of HA or SPF is crosslinked by one or more linker moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the linker moieties are covalently attached to the crosslinked HA or SPF, wherein the one or more linker moieties comprises a PEG chain, wherein the tissue filler has a storage modulus of from 25 Pa to about 1500 Pa (claim 87). The SPF has a polydispersity of between about 1.5 and about 3.0 (claim 100). The tissue filler is injectable (claim 102). The complex viscosity of the tissue filler is from about 1 Pa∙s to about 10 Pa∙s (claim 106). ‘081 also teaches the method, wherein the tissue filler is administered into a dermal region of the subject (claim 89).
However, ‘081 does not teach the modification is obtained using polyglycidyl-PEG. ‘081 does not teach the loss modulus. ‘081 also does not teach the tissue comprises a portion of a wall of an internal organ and the condition is GERD.
Altman et al. teach a HA and silk protein fragments based tissue fillers and methods of the same (Abstract). In one embodiment, the invention is a biocompatible tissue filler comprising a glycosaminoglycan, wherein the glycosaminoglycan is HA, wherein a portion of the HA is cross-linked by cross-linking moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the cross-linked HA comprises a cross-linking moiety comprising a PEG chain (page 3, lines 13 – 14) or a PPG (page 3, line 28). The tissue filler comprising silk protein or silk protein fragments (SPF), wherein the silk protein is silk fibroin, wherein a portion of the SPF are cross-linked (page 8, lines 8 – 17), wherein the cross-linking is obtained using a cross-linking agent that is polyglycidyl-PEG (page 8, lines 24 – 27). In some embodiments, the SPF have a polydispersity of between about 1.5 and about 3.0 (page 7, lines 1 – 2). Altman et al. also disclose that the concentration, size and polydispersity of SPF in the solution may further be altered depending upon the desired use and performance requirements (page 67, lines 30 – 31; page 68, line 1). In one embodiment, the biocompatible tissue filler further includes one or more active agents (page 148, line 3), wherein the active agent is an anesthetic agent, wherein the anesthetic agent is lidocaine (page 15, lines 17 – 23). In some embodiments, the fillers have an injection force of about 5 N to about 25 N, wherein the injection form relates to injection through a 30 G needle (page 55, lines 6 – 10). The tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (page 10, line 24) and loss modulus (G”) from about 5 Pa to about 200 Pa (page 173, lines 9 – 10). The tissue filler also has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (page 11, line 14). The tissue fillers described may be provided in methods of treating one or more conditions in a patient in need thereof (page 183, lines 7 – 8). The condition treated by tissue fillers may include a soft tissue condition (page 183, lines 15 – 16). It may be delivered to soft tissue, such as fibrous tissues, muscles, tendons, subcutaneous tissues, and skin (page 184, lines 11 – 14), or void spaces (page 196, lines 26 – 27). One specific condition is gastroesophageal reflux disease (GERD) (page 184, line 10).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the crosslinking process of producing the biocompatible tissue filler as taught by ‘081 with incorporating polyglycidyl-PEG in view of Altman et al. because Altman et al. teach the examples of using polyglycidyl-PEG as a cross-linker for the production of a biocompatible tissue filler comprising HA and SPF, thereby yielding predictable results. One would have been motivated to incorporate and adjust the rheological properties based on the disclosure of Altman et al. because the incorporation will yield predictable results. As Altman et al. teach other possible uses of the biocompatible tissue filler, one would also have been motivated to apply the similar biocompatible tissue filler to treatment GERD. For the median particle size of the free SPF, one would have performed routine experimentation to discover the best size of the SPF for the optimal treatment characteristics. For the value of Tan(δ) (G”/G’), (G”/G’) is calculated to be 0.4 if G” is 200 and G’ is 500, which both within the range that disclosed by Altman et al. As the patient population and composition are the same, the composition will also achieve “bulking the tissue” after administration, which reads on claim 55. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify the crosslinking process of producing the biocompatible tissue filler as taught by ‘081 with polyglycidyl-PEG in view of Altman et al. because Altman et al. teach that polyglycidyl-PEG has been used successfully as a cross-linker in the production of biocompatible tissue filler comprising HA and SPF.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 11, 20, 23, 44, 53, and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 20 of U.S. Patent No. 12296067B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘067B2 anticipate the claimed invention.
Independent claim 1 is directed to a biocompatible composition comprising silk fibroin or silk fibroin fragments, hyaluronic acid (HA), and polyethylene glycol (PEG) and/or polypropylene glycol (PPG), wherein a portion of the HA is modified or crosslinked by one or more linker moieties comprising one or more PEG and a secondary alcohol, wherein a portion of the silk fibroin are crosslinked, wherein the silk fibroin have a polydispersity of between 1 and about 5.0, and wherein the cross-linking is obtained using a polyglycidyl-PEG. Dependent claim 11 is directed to the composition, wherein the composition further comprising lidocaine. Dependent claim 20 is directed to the composition, wherein the composition has a storage modulus (G’) of from about 5 Pa to about 500 Pa. Dependent claim 23 is directed to the composition, wherein the complex viscosity is between 0 to about 25 Pa∙s. Independent claim 44 is directed to a method of treatment of a disease in a subject in need thereof, wherein the method comprising administering to the subject a composition of claim 1, wherein the composition is injected into a tissue. Dependent claim 53 is directed to the method, wherein the composition is administered into a wall of the tissue. Dependent claim 55 is directed to the method, wherein the administration of the composition causes bulking of the tissue, and wherein the disease is treated by the bulking of the tissue.
‘067B2 teaches a biocompatible tissue filler comprising silk fibroin fragments and HA, wherein a portion of the HA is crosslinked by one or more linker moieties comprising one or more of PEG, PPG, and a secondary alcohol, wherein cross-linking is obtained using as cross-linker, wherein the cross-linker is polyglycidyl-PEG (claim 1). The tissue filler has a portion of the SPF that are crosslinked (claim 2). The SPFs have a polydispersity of between 1 and about 5.0 (claim 4). The tissue filler further comprises lidocaine (claim 9). The tissue filler is a dermal filler and is injectable through 30 G needle (claims 15 and 17 – 18). Finally, ‘067B2 teaches that the tissue filler has a G’ of from about 5 Pa to about 500 Pa and a complex viscosity from about 1 Pa∙s to 10 Pa∙s (claims 19 – 20).
As the patient population and composition are the same, the composition will also achieve “bulking the tissue” after administration, which reads on claim 55.
For these reasons above, ‘067B2 anticipates the claimed invention.
Claims 1, 17 – 18, and 20 – 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 14 of U.S. Patent No. 11660372B2 in view of Altman et al. (WO2019/005848A1, published on January 3, 2019).
Regarding claims1, 17 – 18, and 20 – 23, ‘372B2 teaches a biocompatible tissue filler, comprising HA, an anesthetic agent, and SPF, wherein a portion of HA or SPF is crosslinked by one or more linker moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the linker moieties are covalently attached to the crosslinked HA or SPF, wherein the one or more linker moieties comprise a PEG chain, and wherein the tissue filler has a G’ of from about 25 Pa to about 1500 Pa (claim 1). The SPFs have a polydispersity of between about 1.5 to about 3.0 and a complex viscosity from about 1 Pa∙s to 10 Pa∙s (claims 5 and 14). The tissue filler is injectable (claim 10).
However, ‘372B2 does not teach the modification is obtained using polyglycidyl-PEG. ‘372B2 does not teach the loss modulus.
Altman et al. teach a HA and silk protein fragments based tissue fillers and methods of the same (Abstract). In one embodiment, the invention is a biocompatible tissue filler comprising a glycosaminoglycan, wherein the glycosaminoglycan is HA, wherein a portion of the HA is cross-linked by cross-linking moieties comprising one or more of an alkane or alkyl chain, an ether group, and a secondary alcohol, wherein the cross-linked HA comprises a cross-linking moiety comprising a PEG chain (page 3, lines 13 – 14) or a PPG (page 3, line 28). The tissue filler comprising silk protein or silk protein fragments (SPF), wherein the silk protein is silk fibroin, wherein a portion of the SPF are cross-linked (page 8, lines 8 – 17), wherein the cross-linking is obtained using a cross-linking agent that is polyglycidyl-PEG (page 8, lines 24 – 27). In some embodiments, the SPF have a polydispersity of between about 1.5 and about 3.0 (page 7, lines 1 – 2). Altman et al. also disclose that the concentration, size and polydispersity of SPF in the solution may further be altered depending upon the desired use and performance requirements (page 67, lines 30 – 31; page 68, line 1). In one embodiment, the biocompatible tissue filler further includes one or more active agents (page 148, line 3), wherein the active agent is an anesthetic agent, wherein the anesthetic agent is lidocaine (page 15, lines 17 – 23). In some embodiments, the fillers have an injection force of about 5 N to about 25 N, wherein the injection form relates to injection through a 30 G needle (page 55, lines 6 – 10). The tissue filler has a storage modulus (G’) of from about 25 Pa to about 1500 Pa (page 10, line 24) and loss modulus (G”) from about 5 Pa to about 200 Pa (page 173, lines 9 – 10). The tissue filler also has a complex viscosity from about 1 Pa∙s to about 10 Pa∙s (page 11, line 14). The tissue fillers described may be provided in methods of treating one or more conditions in a patient in need thereof (page 183, lines 7 – 8). The condition treated by tissue fillers may include a soft tissue condition (page 183, lines 15 – 16). It may be delivered to soft tissue, such as fibrous tissues, muscles, tendons, subcutaneous tissues, and skin (page 184, lines 11 – 14), or void spaces (page 196, lines 26 – 27). One specific condition is gastroesophageal reflux disease (GERD) (page 184, line 10).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the crosslinking process of producing the biocompatible tissue filler as taught by ‘372B2 with incorporating polyglycidyl-PEG in view of Altman et al. because Altman et al. teach the examples of using polyglycidyl-PEG as a cross-linker for the production of a biocompatible tissue filler comprising HA and SPF, thereby yielding predictable results. One would have been motivated to incorporate and adjust the rheological properties based on the disclosure of Altman et al. because the incorporation will yield predictable results. For the median particle size of the free SPF, one would have performed routine experimentation to discover the best size of the SPF for the optimal treatment characteristics. For the value of Tan(δ) (G”/G’), (G”/G’) is calculated to be 0.4 if G” is 200 and G’ is 500, which both within the range that disclosed by Altman et al. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify the crosslinking process of producing the biocompatible tissue filler as taught by ‘372B2 with polyglycidyl-PEG in view of Altman et al. because Altman et al. teach that polyglycidyl-PEG has been used successfully as a cross-linker in the production of biocompatible tissue filler comprising HA and SPF.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/JONATHAN S LAU/ Primary Examiner, Art Unit 1693