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 .
Claims 1-20 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 1-20 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 the claimed method wherein the tropoelastin is formulated as a hydrogel, and wherein the tropoelastin hydrogel is administered to the site of a bone defect which is a fracture or void, does not reasonably provide enablement for administration of tropoelastin in other forms or for methods of inducing bone formation other than at bone fractures or voids, such as in individuals suffering from low bone density but not having a bone fracture or void. 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.
Factors to be considered in determining whether a disclosure enables one skilled in the art to make and use the claimed invention in its full scope without resorting to undue experimentation include: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature or complexity of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. See In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
In the instant case, the nature of the invention is complex and unpredictable, involving the effects of complex biochemical molecules on physiological systems. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. This invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology”, Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).
The claims are broad in two respects. First, the method recites an effect of inducing bone formation in an individual. The individual is recited as requiring bone formation, having a bone defect, or having low bone density. Thus, the patient population is very broad, including asymptomatic individuals in need of inducing bone formation (such as post-menopausal women) and individuals having a bone defect other than a fracture or void (such as systemic low bone density in an individual suffering from osteoporosis or osteopenia). The agent being administered is also recited broadly. In most of the claims, there is no limitation regarding the form of tropoelastin, and thus the claims include administration of tropoelastin protein in any solid or liquid form; cross-linked or uncross-linked or both; and with or without any carriers, cells, or other active or inactive ingredients.
The scope of detailed guidance and working examples provided by the specification are decidedly narrower. The specification contains assertions that the claimed method works, as well as reference to publication describing sequences of tropoelastin proteins or fragments that have desirable properties in an elastic hydrogel. The working examples are limited to the effects of tropoelastin hydrogels on bone defects which are voids. However, it is generally accepted that fractures are very similar to voids, with the difference being in the distance between the ends of the bone. Example 1 describes the bone formation enhancing effects of TE-PNPHO hydrogel on a bone void. Example 6 indicates that the TE-PNPHO hydrogel used in the example has a particular dosage, but does not indicate what form or sequence of tropoelastin was used. Example 2 pertains to the injectability, cytocompatibility, and cellular infiltration of TE-PNPHO hydrogel. Example 3 discloses the bone formation effects of TE-PNHPO and TE-HA hydrogels on bone defects which are voids. Again, no information is provided regarding the sequence of tropoelastin for the TE-PNPHO as per Example 6. Regarding TE-HA, Example 5 indicates that recombinant human tropoelastin was used, and provides dosages. Example 4 pertains to a bone void defect model treated with tropoelastin, but the sequence of the tropoelastin as well as the formulation and dosage of the “cylindrical grafts” are not disclosed. Accordingly, the specification only provides working examples and detailed guidance for the ordinary skilled artisan to make and use recombinant human tropoelastin hydrogels for the formation of bone in fracture and void type defects by locally administering the TE-hydrogel to the site of the defect. The guidance and working examples are not pertinent to the treatment of low bone density or systemic administration of tropoelastin for the treatment of such.
The state of the art acknowledges that tropoelastin hydrogels are useful for the treatment of bone defects such as fractures. Also, several forms of tropoelastin were known in the prior art. See WO 2012/068619 A1, WO 2014/063194 A1, and WO 2014/089610 A1 (IDS 4/22/2024).
Due to the large quantity of experimentation necessary to achieve bone formation using forms of tropoelastin other than hydrogels to treat bone defects that are fractures or voids, the lack of direction/guidance presented in the specification regarding the same, the absence of working examples directed to the same, the complex nature of the invention, the contradictory state of the prior art, the unpredictability of the effects of complex biochemical molecules on physiological systems, and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 7 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Summer-Knudsen, WO 2012/068619 A1 (IDS 4/22/2024).
Summer-Knudsen teaches a method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual, thereby inducing bone formation in the individual. See abstract; p. 2 li. 33-35; p. 3 li. 28-34; p. 31 li. 15 - p. 32 li. 5. It is noted that the instant specification indicates that 1.5 mg/ml to 400 mg/ml of tropoelastin is therapeutically effective (p. 18). Summer-Knudsen teaches 250 µl of a 200 mg/ml solution of tropoelastin in 1 ml total formulation, which works out to be 50 mg/ml. See Example 6. Example 9 provides a different formulation that also results in a 50 mg/ml concentration of tropoelastin. This is relevant to claim 1.
Regarding claim 7, injection is taught at p. 2 li. 33-35.
Claims 1-15 and 20 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Annabi et al., WO 2014/063194 A1 (IDS 4/22/2024).
Annabi teaches a method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual, thereby inducing bone formation in the individual. See abstract; p. 2 li. 25 - p. 4 li. 8; p. 6 li. 6-7; p. 33 li. 13-25, p. 51 li. 15-24. Please note the wide range of tropoelastin concentrations taught at p. 33 li.13-25. It can be assumed that many if not all of these are at a therapeutically effective concentration. This is relevant to claim 1.
Regarding claims 2-6, 8-12, 14, 15, Annabi teaches the use of the tropoelastin hydrogels in three dimensional forms to provide reparative, restorative, replacement, and/or regenerative therapy for bone remodeling or mending of all types of bones. See p. 51 li. 20-24, p. 64 li. 12-21, p. 65 li. 1-14. This implies bone defects that are fractures or voids as well as application at the site of the fracture or void which would contain the bone callus as well as periosteal surfaces.
Regarding claims 7 and 13, direct application to the site by injection is taught at p. 68 li. 6-10.
Regarding claim 20, the tropoelastin named SHELᵟ26A, also known as SHELD26A, was used in Example 1.
Claims 1-6, 8-12, 14, and 15 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Weiss et al., WO 2014/089610 A1 (IDS 4/22/2024).
Weiss teaches a method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual, thereby inducing bone formation in the individual. See abstract, p. 5 li. 1-3, p. 27 li. 15-28, p. 33 li. 3-20, p. 39 li. 21 - p. 40 li. 2, p. 44 li. 23-29. Please note that concentrations of tropoelastin including those indicated in the specification as being therapeutically effective, are taught by Weiss at p. 18 li. 9-20. This is relevant to claim 1.
Regarding claims 2-6, 8-12, 14, and 15, Weiss teaches the use of the tropoelastin hydrogels in three dimensional forms as a bone filling material. See p. 44 li. 23-29. This implies bone defects that are fractures or voids as well as application at the site of the fracture or void which would contain the bone callus as well as periosteal surfaces.
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.
Claims 1-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Annabi et al., WO 2014/063194 A1 (IDS 4/22/2024) in view of Rousseau, WO 00/15836 (IDS 4/22/2024).
As discussed above, Annabi teaches a method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual, thereby inducing bone formation in the individual. See abstract; p. 2 li. 25 - p. 4 li. 8; p. 6 li. 6-7; p. 33 li. 13-25, p. 51 li. 15-24. Please note the wide range of tropoelastin concentrations taught at p. 33 li.13-25. It can be assumed that many if not all of these are at a therapeutically effective concentration. This is relevant to claim 1. Regarding claim 2, Annabi teaches the use of the tropoelastin hydrogels in three dimensional forms to provide reparative, restorative, replacement, and/or regenerative therapy for bone remodeling or mending of all types of bone defects in which bone formation is required. See p. 51 li. 20-24, p. 64 li. 12-21, p. 65 li. 1-14. This implies application at the site of the bone defect which would contain the bone callus as well as periosteal surfaces. Regarding claim 20, the tropoelastin named SHELᵟ26A, also known as SHELD26A, was used in Example 1.
Annabi does not explicitly teach a method of inducing formation of bone by administering tropoelastin to an individual having a bone defect which is low bone density. However, Rousseau teaches that individuals suffering from low bone density, such as those suffering from osteoporosis, commonly have bone fractures. See p. 102. Accordingly, Rousseau suggests a patient population having both osteoporosis and bone fractures would benefit from administration of a therapeutic agent that induces bone formation as claimed.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant application was filed to modify the method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual as taught by Annabi, by applying the technique to an individual having low bone density and accompanying bone fractures as disclosed by Rousseau with a reasonable expectation of success. The motivation to do so is provided by the teachings of Rousseau regarding the effects of fractures and low bone density on an individual’s health.
Claims 1- 20 are rejected under 35 U.S.C. 103 as being unpatentable over Annabi et al., WO 2014/063194 A1 (IDS 4/22/2024) in view of Rousseau, WO 00/15836 (IDS 4/22/2024) as applied to claims 1-18, and 20 above, and further in view of Man et al., 2010 (instant PTO-892).
As discussed above, Annabi in view of Rousseau suggests a method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual, thereby inducing bone formation in the individual, wherein the individual has a bone defect that includes low bone density.
Annabi does not teach administration of the tropoelastin by micro-drilling.
Man teaches how micro-drilling is a common surgical procedure, and how it is desirable to have new bone growth in and around the micro-drilled hole for better stability. See Abstract and Introduction sections.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant application was filed to modify the method of inducing formation of bone in an individual including the steps of providing an individual requiring bone formation and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone in the individual as taught by Annabi, by applying the technique to an individual having low bone density and accompanying bone fractures as disclosed by Rousseau, and further to utilize micro-drilling as taught by Man with a reasonable expectation of success. The motivation to do so is provided by the teachings of Rousseau regarding the effects of fractures and low bone density on an individual’s health, and the teachings of Man that micro-drilling can result in enhanced bone cell formation and thus enhance adhesion strength of medical implants.
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 1-15 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,736,942 B2. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Both sets of claims recite methods of inducing formation of bone in an individual including the steps of providing an individual having a bone fracture or void requiring bone formation, and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone, and wherein the tropoelastin is administered via injection. Both claim sets include limitations regarding formulations of a gel, putty or paste. Both claim sets recite administration to a bone callus or a periosteal surface. Both claims sets include a tropoelastin that is SHELᵟ26A.
The claim sets differ in that the instant claims recite a broader genus for the patient population (wherein the instantly claimed patient population is in need of bone formation, but not necessarily having a bone fracture or void in claims 1 and 2), and the administered tropoelastin (wherein the instantly claimed tropoelastin can be any type and not just uncross-linked tropoelastin as per the patented claims). However, in each case, the subgenus recited in the patented claims anticipates the broader genus recited in the instant claims.
Accordingly, issuance of the instant claims without a terminal disclaimer raises the possibility of an unjustified or improper timewise extension of the “right to exclude” granted by a patent, and possible harassment by multiple assignees.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,736,942 B2 in view of Rousseau, WO 00/15836 (IDS 4/22/2024) and Man et al., 2010 (instant PTO-892).
As discussed above, both sets of claims recite methods of inducing formation of bone in an individual including the steps of providing an individual having a bone fracture or void requiring bone formation, and providing a therapeutically effective amount of tropoelastin to the individual to induce the formation of bone, and wherein the tropoelastin is administered via injection. Both claim sets include limitations regarding formulations of a gel, putty or paste. Both claim sets recite administration to a bone callus or a periosteal surface.
The claim sets differ in that the instant claims recite a broader genus for the patient population (wherein the instantly claimed patient population is in need of bone formation, but not necessarily having a bone fracture or void in claims 1 and 2), and the administered tropoelastin (wherein the instantly claimed tropoelastin can be any type and not just uncross-linked tropoelastin as per the patented claims). However, in each case, the subgenus recited in the patented claims anticipates the broader genus recited in the instant claims.
Claims 15-19 further differ from the patented claims in that the instant claims recite a patient population wherein the bone defect is low bone density, and wherein the tropoelastin is administered via micro-drilling. However, Rousseau evidences that individuals suffering from low bone density, such as those suffering from osteoporosis, commonly have bone fractures. See p. 102. Accordingly, Rousseau suggests a patient population having both osteoporosis and bone fractures would benefit from administration of a therapeutic agent that induces bone formation as claimed. Also, Man et al. review how micro-drilling is a common surgical procedure, and how it is desirable to have new bone growth in and around the micro-drilled hole for better stability. See Abstract and Introduction sections.
Accordingly, the patented claims suggest the instant claims in view of the prior art. Thus, issuance of the instant claims without a terminal disclaimer raises the possibility of an unjustified or improper timewise extension of the “right to exclude” granted by a patent, and possible harassment by multiple assignees.
Conclusion
No claims are allowed.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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