DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Claims 1-81 have been cancelled. Claims 85 and 108 have been amended.
Claims 82-121 are pending and under examination.
2. The rejection of claim 83 under 35 U.S.C. 112(b) is withdrawn in response to applicant’s arguments.
Specification
3. The claim listing is objected to because claims 85 and 108 have been amended but they are incorrectly identified as “Previously Presented”.
Claim Objections
4. Applicant is advised that should claims 82, 84, 87, and 94 be found allowable, claims 100, 105, 106, and 109 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
The arguments have been considered but not found persuasive. Although claim 100 does not recite that the material is stable for at least one month, Pritchard (Biopolymers, 2012, 97: 479-498) discloses that silk fibroin is inherently stable (see p. 480, paragraph bridging columns 1 and 2).
5. Claim 108 is objected to because of the recitation “at least dimension”. Appropriate correction to “at least one dimension” is required.
Double Patenting
6. 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.
7. Claims 82-121 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,376,329. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same composition comprising the same population of silk fibroin fragments. The instant specification discloses that the additive has a concentration of at least 5%, that the composition comprises silk fibroin between 0.1 and 90% by weight, and that the composition could be lyophilized (see [0128]; [0161]; [0180]; [0363]). The patent specification discloses that at least 50% of the silk fibroin fragments could have a size of 3.5-15 kDa or 110-120 kDa, the composition could be in the form of particles having a particle size of 0.1 to 250 µm and that the additive/therapeutic agent could be lidocaine (see column 2, lines 53-58; column 22, lines 7-23; column 24, line 63 through column 25, line 20; column 51, lines 15-26; column 81). Thus, the patent claims and the instant claims are obvious variants.
Claim Rejections - 35 USC § 103
8. 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.
9. Claims 82-94 and 96-112 are rejected under 35 U.S.C. 103 as being unpatentable over Nam et al. (J. Appl. Polym. Sci., 2001, 81: 3008-3021), in view of both Chen (Thesis, 2004; Abstract) and Pritchard et al. (Biopolymers, online 23 January 2012, 97: 479-498).
Nam et al. teach an aqueous solution consisting of a population of silk fibroin fragments in water (i.e., a carrier), where the majority of the fragments (i.e., more than 50%) in the population have a molecular weight in the range of 20 to 50 kDa and where at least 50% of the fragments in the population have a discrete or a continuous molecular weight distribution within the range (claims 82, 88-92, 94, 100, 101, and 109) (see p. 3009; p. 3019; Fig. 14). Although the silk fibroin solution comprises a small proportion of silk fragments having a molecular weight between 120 and 200 kDa, Nam et al. do not specifically teach that this proportion is between 5 and 35% (claims 82, 100, 110-112). However, MPEP § 716.02 states that “[a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986)”. In the instant case, there is no evidence of record that the claimed proportion result in an unexpected property when compared to the very similar proportion taught by Nam et al.
Nam et al. teach that the silk fibroin solution can be formulated as a powder for drug delivery, where the powder comprises fibroin particles having a size of about 1 µm (claims 83, 96-98, 102, 104, and 108) (see Abstract; p. 3009, column 1, second and third paragraphs; p. 3020, paragraph bridging columns 1 and 2). One of skill in the art would have found obvious to formulate the solution Nam et al. with a drug and further use the resulting formulation to obtain a powder to achieve the predictable result of obtaining a therapeutic composition suitable for drug delivery (claims 84, 86, and 105).
Nam et al. do not teach that the drug is lidocaine (claims 87 and 106). Chen teach that lidocaine-loaded microparticles could be used for efficient anesthetic effect (see Abstract). Using lidocaine as the drug would have been obvious to one of skill in the art to achieve the predictable result of obtaining a composition suitable to be used as an anesthetic, when anesthetic delivery was desired.
Nam et al. do not teach a vaccine (claims 84, 86, and 107). Pritchard et al. teach silk biomaterials as attractive carriers for vaccines due to the capacity of silk to stabilize the incorporated sensitive compounds (see p. 480, paragraph bridging columns 1 and 2; p. 481, column 1, first full first paragraph; paragraph bridging p. 496 and 497). One of skill in the art would have found obvious to modify the composition of Nam et al. by replacing the drug with a vaccine to achieve the predictable result of obtaining a composition suitable to induce immune responses, when inducing immune responses was desired.
With respect to stability (claims 82, 99, and 101), Pritchard et al. teach that silk fibroin is inherently stable to changes in temperature and moisture, it is mechanically robust, and offers a highly stabilizing environment for the incorporated agents (see p. 480, paragraph bridging columns 1 and 2). Based on these teachings, one of skill in the art would have reasonably concluded that the composition of Nam et al. is stable for at least one month.
With respect to solubility (claims 93 and 103), Nam et al. teach that the particle preparation parameters have a significant influence on solubility, and thus, control release (see p. 3009, column 1, second and third paragraph; p. 3020, paragraph bridging columns 1 and 2). One of skill in the art would have found obvious to use routine experimentation and vary the parameters with the reasonable expectation that doing so would result in compositions exhibiting the desired solubility and drug release profiles.
With respect to claim 85, one of skill in the art would have found obvious to use routine experimentation and vary the amount of active agent in the composition with the
Reasonable expectation that doing so would identify the optimal amounts for delivery. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed range was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
10. Claims 82, 88-92, 94-98, 100, 101, 108-112, 115, 118, and 121 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (J. Nanoparticle Res., 2007, 9: 885-900), in view of Pritchard et al.
Zang et al. teach two aqueous solutions (i.e., carriers) each comprising a population of silk fibroin fragments having continuous molecular weight distribution within the range of 8-120 kDa or within the range of 8-100 kDa; the majority of the fragments (i.e., more than 50%) in both populations have a molecular weight within the range of 8-15 kDa. Zang et al. teach that the silk fibroins fragments are in the form of nanoparticles having a size of 35-125 nm (claims 82, 88-92, 94-98, 100, 101, 108, 109, 115, 118, and 121) (see p. 890). Although the silk fibroin solutions comprise a small proportion of silk fragments having a molecular weight between 120 and 200 kDa, Zhang et al. do not specifically teach that this proportion is between 5 and 35% (claims 82, 96, 100, and 110-112). However, MPEP § 716.02 states that “[a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986)”. In the instant case, there is no evidence of record that the claimed proportion result in an unexpected property when compared to the very similar proportion taught by Zhang et al.
With respect to stability (claims 82, 99, and 101), Pritchard et al. teach that silk fibroin is inherently stable to changes in temperature and moisture, it is mechanically robust, and offers a highly stabilizing environment for the incorporated agents (see p. 480, paragraph bridging columns 1 and 2). Based on these teachings, one of skill in the art would have reasonably concluded that the composition of Zhang et al. is stable for at least one month.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
11. Claims 82-84, 86, 88, 89, 91-105, and 107-121 are rejected under 35 U.S.C. 103 as being unpatentable over Wray et al. (J. Biomed. Mater. Res. Part B: Appl. Biomater., 2011, 99B: 89-101), in view of Pritchard et al. and Marelli et al.
Wray et al. teach an aqueous solution consisting of a population of silk fibroin fragments in water (i.e., a carrier), where the majority of the fragments (i.e., more than 50%) in the population have a molecular weight in the range of 41-120 and where the fragments in the population have a continuous molecular weight distribution within the range. Wray et al. teach obtaining the aqueous solution without using methanol or ethanol. Wray et al. teach air-drying part of the solution (claims 82, 83, 89, 91-94, 100, 103, 109, 113, and 119) (see paragraph bridging p. 90 and 91; p. 93). Although the silk fibroin solution comprises a small proportion of silk fragments having a molecular weight between 120 and 200 kDa, Wray et al. do not specifically teach that this proportion is between 5 and 35% (claims 82, 100, and 110-112). However, MPEP § 716.02 states that “[a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986)”. In the instant case, there is no evidence of record that the claimed proportion result in an unexpected property when compared to the very similar proportion taught by Wray et al.
With respect to claims 96-99, 108, 111, 116, and 117, Pritchard et al. teach that silk fibroin can be formulated into powder or particles (having a size of less than 150 µm or less than 100 nm) for stabilizing agents of interest, the particle have (see p. 481, column 1, second paragraph; Table I on p. 484-485; p. 492, Table IV). Using the aqueous solution to form microparticles, nanoparticles, or powder would have been obvious to one of skill in the art to achieve the predictable result of obtaining particles suitable for the stabilization of agents of interest (claims 84, 86, 102, 104, and 105). With respect to claim 107, Pritchard et al. teach that silk fibroin can be used as a carrier for vaccines (see paragraph bridging p. 496 and 497). One of skill in the art would have found obvious to use the micro- or nanoparticles to encapsulate a vaccine to achieve the predictable result of obtaining a composition suitable for immunization.
With respect to stability (claims 82 and 101), Pritchard et al. teach that silk fibroin is inherently stable to changes in temperature and moisture, it is mechanically robust, and offers a highly stabilizing environment for the incorporated agents (see p. 480, paragraph bridging columns 1 and 2). Based on these teachings, one of skill in the art would have reasonably concluded that the composition of Wray et al. is stable for at least one month.
Wray et al. do not specifically teach that at least 50% of the fragments have a molecular weight of 19-50 kDa (claim 88), 100-120 kDa (claims 114 and 120), or 3.5-15 kDa (claims 95, 115, 118, and 121). However, Wray et al. teach that the degumming time determines the molecular weight of the silk fibroin fragments, where the molecular weight affects properties such as thermal stability and the formation of useful biomaterial products. Wray et al. teach that degumming could be used to tailor morphological characteristics and the degradation profiled of silk fibroin biomaterials to match the specific needs for the tissue being regenerated (see Abstract; p. 93-94; paragraph bridging p. 97 and 98). Marelli et al. teach that silk fibroin fragments having a molecular weight of 10 kDa promote biomineralization (see Abstract; p. 104). One of skill in the art would have found obvious to use routine experimentation and vary the degumming time with the reasonable expectation that doing so would result in fragments suitable for the desired applications, such as tissue regeneration and biomineralization. As per MPEP 2144.05 II, "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed molecular weights was other than routine or that their presence would lead to properties considered unexpected in any way as compared to the closest prior art.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
12. The argument that Nam provides minimal disclosure regarding the molecular weights is not found persuasive.
Nam provides the necessary disclosure regarding the molecular weight of the silk fibroin fragments. Fig. 14 in Nam shows that the majority of the fragments obtained by a dissolution time of 12, 24, or 48 h have a molecular weight within the range of 15-50 kDa. The range disclosed by Nam anticipates the limitation of at least 50% by weight of the fragments having a molecular weight within the range of 3.5-120 kDa (claims 82, 96, and 100) or 19-50 kDa (claim 88).
Fig. 14 also shows the presence of a very small percentage of fragments having a molecular weight above 50 kDa. While Nam does not specifically disclose that the fragments present in this very small percentage have a molecular weigh between 120-200 kDa, there is no evidence of record that the presence of the claimed proportion of fragments result in an unexpected property over Nam.
It is also noted that the rejection does not state and the examiner did not assert Nam teaches that the silk fibroin solution comprises a small proportion of fragments having molecular weights within the range 120-200 kDa, as argued by the applicant.
The arguments addressing Zhang and Wray are not found persuasive for the same reasons as above.
The argument that none of Nam, Zhang, and Wray includes protein standards with molecular weights of 120 and 200 kDa is not found persuasive for the reasons set forth above.
The applicant argues that none of Nam, Zhang, and Wray includes a protein standard with molecular weights of 3.5 kDa.
This is not found persuasive because none of Nam, Zhang, and Wray has to disclose such. Nam discloses a majority of fragments between 15-50 kDa; Zhang discloses a majority of fragments between 8-15 kDa; Wray discloses a majority of fragments between 41-120. Each of these ranges anticipates the claimed range.
The argument regarding the subjective nature of the observer is not found persuasive. It is clear from the figures in Nam, Zhang, and Wray that the majority of the fragments is within the ranges mentioned above.
While the fragments are spread out and it is hard to differentiate individual molecular weights, the claims do not require differentiating individual molecular weights; the molecular weights are spread out within the claimed range of 3.5-129 kDa. The rejections do not state that Nam, Zhang, and Wray differentiate individual molecular weights. The rejection states that the fragments are spread out within the ranges of 15-50 kDa; 8-15 kDa; and 41-120, which anticipate the claimed range.
For these reasons, the argument that Nam does not teach or exemplifies a method assessing the intensity of the bands is not found persuasive. Furthermore, since the rejection is an obviousness-type rejection, Nam does not have to exactly teach the claimed fragment distribution.
The arguments regarding the methods to generate the fibroin fragments, the PTAB decision, and claims 89 and 90 are not new and were previously addressed. It is also noted that the claims only require a certain distribution which is rendered obvious by the cited prior art. Furthermore, the only property recited in the claims is stability, which is a property inherent to silk fibroin. The applicant did not provide any evidence indicating that Nam’s preparation method changes the inherent stability of silk fibroin.
With respect to the clarity in Nam’s Fig. 14, the specification defines "discrete molecular weight distribution" as a distribution of molecular weight having certain sub-ranges between the specified range (see [0116]). Lines (d) and (e) clearly show the presence of a molecular weight wide band below 21.5 kDa (a sub-range within the 20-50 kDa range, i.e., a discrete molecular weight distribution) and also a continuous molecular weight distribution above this band. Thus, Fig. 14 shows that the low molecular weight fragments comprise a population having a continuous distribution and a population of fragments having a discrete distribution.
The arguments regarding claims 88, 95, and 114 are not found persuasive.
Claim 88 recite a range of 19-50 kDa. Claim 95 recites a range of 3.5-15 kDa. Claim 114 recites a range of 100-120 kDa.
Claims 82 and 88 are properly grouped together in the rejection over Nam because Nam teaches the range of 15-50 kDa, which anticipates the ranges recited in both claims.
Claim 82 and 95 are properly grouped together in the rejection over Zhang because Zhang teaches the range of 8-120 kDa, which anticipates the ranges recited in both claims.
Claim 114 is separately rejected over Wray. With respect to routine optimization of the degumming time to achieve the distribution recited in claim 114, the applicant argues that the examiner did not establish a nexus between the degumming time and concentration or temperature. However, Wray provides the teachings and the reasonable expectation of success necessary for one of skill in the art to obtain fragments with desired size distribution.
Conclusion
13. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILEANA POPA whose telephone number is (571)272-5546. The examiner can normally be reached 8:00 am to 4:30 pm.
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/ILEANA POPA/Primary Examiner, Art Unit 1633