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 .
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 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.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Dec. 25, 2025 has been entered. All arguments have been fully considered.
Status of the Claims
Claims 17, 18, 20 and 23-32 are currently pending.
Claims 1-16, 19 and 21-22 are cancelled.
Claims 17, 18, 20 and 23-32 have been considered on the merits.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are maintained.
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 17, 18, 20 and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. (Bio-Design and Manufacturing, published Jan. 25, 2022) (ref. of record) in view of Ho et al. (Stem cells translational medicine, 2016) (ref. of record), Zhang et al. (Pharmacological Research, 2021) (ref. of record) and Liu et al. (Artificial cells, Nanomedicine, and Biotechnology, 2018) (ref. of record).
With respect to claim 17, Sun teaches a method of augmenting and stabilizing fractured vertebral bodies by administering an effective amount of a composition containing polymethyl methacrylate (PMMA) bone cement and oxidized hyaluronic acid and carboxymethyl chitosan in situ cross-linking hydrogel or a PMMA-hydrogel hybrid (abstract and pg. 320 Col. 1 para. 2). Sun teaches the administration of PMMA-hydrogel hybrid loaded with BMP-2 to rabbit femoral condyle bone-defect models results in enhanced bone formation and the composition is biodegradable (abstract). With respect to claim 17, Sun teaches injecting the composition into the bone site where bone regeneration needs to promoted (pg. 322-323 bridging para. and pg. 326 Col. 1 para. 1). Although, Sun does not explicitly teach that the PMMA is surrounded or encapsulated by the hydrogel as claim 17 is being interpreted as explained above. Sun teaches the mixing of the hydrogel and PMMA to form a solution (pg. 320 Col. 2 para. 1).
With respect to claim 17, Sun teaches the PMMA and hydrogel are mixed where there was 5-25% hydrogel of the total volume and the PMMA concentration is 2 g/mL (pg. 320 Col. 2 para. 1). Although Sun is silent with respect to the volume ratio of hydrogel to PPMA and does not teach the ratio range of 3 to 5:1 as recited in claim 17, one of ordinary skill in the art would recognize that the volume ratio of hydrogel to PPMA is a result effective variable and that the ratio would be matter of routine optimization depending on the desired consistence of the final product as evidenced by Sun. Sun reports that the transparency, the setting temperatures, compressive strength, the injectability and degradation rate of the hybrid cements depends on the ratio of PMMA and hydrogel (pg. 323 Col. 1 last para to Col. 2 para. 3).
Sun does not teach the method where the composition further contains stem cell spheroids as recited in claim 17. Similarly, Sun does not teach the stem cells are human-derived pluripotent stem cells (PSC), embryonic stem cells (ESC), mesenchymal stem cells (MSCs), adult stem cells (ASC) or induced pluripotent stem cells (iPSC) as recited in claim 23 and are mesenchymal stem cells (MSCs) as recited in claim 24. However, Ho teaches cells cultured as three-dimensional spheroids more accurately mimics the physiological cellular niche and may precondition the cells residing in the inner core to hypoxic conditions (pg. 773-774 bridging para.). Ho teaches mesenchymal stem cell (MSC) spheroids exhibits improved therapeutic potential in vitro compared with dissociated MSCs (pg. 773 significance). Additionally, Ho teaches that cell delivery using adhesive biomaterials promotes cell retention and function (pg. 773 significance). In further support, Zhang teaches the combination of scaffolds and MSCs can be key players in the process of bone healing in difficult clinical settings (pg. 3 Col. 1 para. 2). Zhang teaches adding stem cells to the material improves the speed and quality of defect repair (pg. 6 Col. 1 last para.). Additionally, Zhang teaches bone diseases that can be treated with stem cells include osteoarthritis, osteoporosis and cancer (pg. 5 Col. 1 last para.). Accordingly, one of ordinary skill in the art at the time of filing of the claimed invention would have been motivated to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids for the known healing benefits of MSCs on bone repair as taught by Zhang and the improved therapeutic potential of the cells when cultured as spheroids as taught by Ho. It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to combine the instant ingredients for their known benefit on repairing and treating bone defects and diseases, as disclosed by the cited references above, since each is well known in the art for their claimed purpose. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids and where the cells are MSCs since Ho teaches that cell delivery using adhesive biomaterials promotes cell retention and function and Zhang teaches the use of scaffold material in delivery of MSC spheroids to tissue in vivo.
Further with respect to claim 17, Sun teaches the hydrogel comprising 5% w/v chitosan and 5% w/v oxidized hyaluronic acid (would give a 1:1 weight ratio which is within the claimed range of the ratio of glycol chitosan to oxidized hyaluronate of 1 to 10:1 (pg. 320 Col. 2 para. 1). Sun does not teach the method where chitosan is glycerol chitosan. However, Liu teaches a method of treating cartilage tissue defects by injecting a composition comprising a hydrogel composed of glycol chitosan and oxidized hyaluronic acid and BMSCs (bone marrow stem cells) (abstract and pg. S723 last para). Liu teaches that glycol chitosan has good solubility in water and HA (hyaluronic acid) is high molecular-weight polysaccharide that supports cell proliferation (pg. S721 Col. 2 para. 1). Liu further teaches mixing the hydrogel with BMSCs (pg. S723 Col.1-2 bridging para.). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Sun so that the chitosan is glycol chitosan for the benefit of having good solubility in water as taught by Liu. Additionally, one of ordinary skill in the art would have been motivated to modify the teachings of Sun in such a way that the chitosan is glycol chitosan for the purpose being able to form a hydrogel for promoting bone regeneration, since methods of using glycol chitosan for hydrogels for injecting into subject to repair tissue were known as taught by Liu. Such a modification merely involves the substitution of one known type of chitosan for another for the forming of an injectable hydrogel and would have yielded predictable results (e.g. the forming of an injectable chitosan/HA hydrogel to one of ordinary skill in the art.
Although, Sun does not teach the bone disease or condition being treated is one of those listed in claim 18, Sun does teach the need for injectable bone cements for osteoporotic vertebral compression fractures in the elderly (pg. 319 Col. 1 para. 1) and PMMA bone cement is known for use in augmenting and stabilizing fractured vertebral bodies (abstract). Accordingly, one of ordinary skill in the art at the time of filing of the claimed invention would have been motivated to modify the method of Sun to including additional known bone diseases or conditions in need of bone regeneration and treatment such as fractures and osteoporosis. One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification, since Sun reports that PMMA compositions are well known for their use in repairing bone.
With respect to claim 20, Sun teaches the composition further containing BMP-2, a osteogenic agent (abstract and pg. 320 Col. 1 para. 2).
With respect to claims 25 and 26, Sun teaches the PMMA-hydrogel hybrid loaded BMP-2 composition is injected into rabbit femoral bone-defect models biodegradable (is a composition and injected into a site where bone disease has progressed) (abstract, pg. 322-323 bridging para. and pg. 326 Col. 1 para. 1). With respect to claim 27, Sun teaches the composition enhances femur bone formation (cortical bone) (abstract).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claims 17, 18, 20 and 23-32 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. (Bio-Design and Manufacturing, published Jan. 25, 2022) (ref. of record) in view of Ho et al. (Stem cells translational medicine, 2016) (ref. of record), Zhang et al. (Pharmacological Research, 2021) (ref. of record), Liu et al. (Artificial cells, Nanomedicine, and Biotechnology, 2018) (ref. of record) and Sa et al. (RSC Advances, 2015) (ref. of record).
With respect to claim 17, Sun teaches a method of augmenting and stabilizing fractured vertebral bodies by administering an effective amount of a composition containing polymethyl methacrylate (PMMA) bone cement and oxidized hyaluronic acid and carboxymethyl chitosan in situ cross-linking hydrogel or a PMMA-hydrogel hybrid (abstract and pg. 320 Col. 1 para. 2). Sun teaches the administration of PMMA-hydrogel hybrid loaded with BMP-2 to rabbit femoral condyle bone-defect models results in enhanced bone formation and the composition is biodegradable (abstract). With respect to claim 17, Sun teaches injecting the composition into the bone site where bone regeneration needs to promoted (pg. 322-323 bridging para. and pg. 326 Col. 1 para. 1). Although, Sun does not explicitly teach that the PMMA is surrounded or encapsulated by the hydrogel as claim 17 is being interpreted as explained above. Sun teaches the mixing of the two component to form a solution (pg. 320 Col. 2 para. 1), therefore, one would expect the same result of the PMMA being surrounded or encapsulated by the hydrogel.
With respect to claims 17 and 29, Sun teaches the PMMA and hydrogel are mixed where there was 5-25% hydrogel of the total volume and the PMMA concentration is 2 g/mL (pg. 320 Col. 2 para. 1). Although Sun is silent with respect to the volume ratio of hydrogel to PPMA and does not teach the ratio range of 1:1 to 5:0 recited in claims 17 and 29, one of ordinary skill in the art would recognize that the volume ratio of hydrogel to PPMA is a result effective variable and that the ratio would be matter of routine optimization depending on the desired consistence of the final product as evidenced by Sun. Sun reports that the transparency, the setting temperatures, compressive strength, the injectability and degradation rate of the hybrid cements depends on the ratio of PMMA and hydrogel (pg. 323 Col. 1 last para to Col. 2 para. 3).
Sun does not teach the method where the composition further contains stem cell spheroids as recited in claim 17. Similarly, Sun does not teach the stem cells are human-derived pluripotent stem cells (PSC), embryonic stem cells (ESC), mesenchymal stem cells (MSCs), adult stem cells (ASC) or induced pluripotent stem cells (iPSC) as recited in claims 23 and 30 and are mesenchymal stem cells (MSCs) as recited in claims 24 and 31. However, Ho teaches cells cultured as three-dimensional spheroids more accurately mimics the physiological cellular niche and may precondition the cells residing in the inner core to hypoxic conditions (pg. 773-774 bridging para.). Ho teaches mesenchymal stem cell (MSC) spheroids exhibits improved therapeutic potential in vitro compared with dissociated MSCs (pg. 773 significance). Additionally, Ho teaches that cell delivery using adhesive biomaterials promotes cell retention and function (pg. 773 significance). In further support, Zhang teaches the combination of scaffolds and MSCs can be key players in the process of bone healing in difficult clinical settings (pg. 3 Col. 1 para. 2). Zhang teaches adding stem cells to the material improves the speed and quality of defect repair (pg. 6 Col. 1 last para.). Additionally, Zhang teaches bone diseases that can be treated with stem cells include osteoarthritis, osteoporosis and cancer (pg. 5 Col. 1 last para.). Accordingly, one of ordinary skill in the art at the time of filing of the claimed invention would have been motivated to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids for the known healing benefits of MSCs on bone repair as taught by Zhang and the improved therapeutic potential of the cells when cultured as spheroids as taught by Ho. It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to combine the instant ingredients for their known benefit on repairing and treating bone defects and diseases, as disclosed by the cited references above, since each is well known in the art for their claimed purpose. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids and where the cells are MSCs since Ho teaches that cell delivery using adhesive biomaterials promotes cell retention and function and Zhang teaches the use of scaffold material in delivery of MSC spheroids to tissue in vivo.
With respect to claims 17 and 28, Sun teaches the hydrogel comprising 5% w/v chitosan and 5% w/v oxidized hyaluronic acid (would give a 1:1 weight ratio which is within the claimed range of the ratio of glycol chitosan to oxidized hyaluronate of 1 to 10:1 (pg. 320 Col. 2 para. 1). Sun does not teach the method where chitosan is glycerol chitosan. However, Liu teaches a method of treating cartilage tissue defects by injecting a composition comprising a hydrogel composed of glycol chitosan and oxidized hyaluronic acid and BMSCs (bone marrow stem cells) (abstract and pg. S723 last para). Liu teaches that glycol chitosan has good solubility in water and HA (hyaluronic acid) is high molecular-weight polysaccharide that supports cell proliferation (pg. S721 Col. 2 para. 1). Liu further teaches mixing the hydrogel with BMSCs (pg. S723 Col.1-2 bridging para.). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Sun so that the chitosan is glycol chitosan for the benefit of having good solubility in water as taught by Liu. Additionally, one of ordinary skill in the art would have been motivated to modify the teachings of Sun in such a way that the chitosan is glycol chitosan for the purpose being able to form a hydrogel for promoting bone regeneration, since methods of using glycol chitosan for hydrogels for injecting into subject to repair tissue were known as taught by Liu. Such a modification merely involves the substitution of one known type of chitosan for another for the forming of an injectable hydrogel and would have yielded predictable results (e.g. the forming of an injectable chitosan/HA hydrogel to one of ordinary skill in the art.
Although, Sun does not teach the bone disease or condition being treated is one of those listed in claim 18, Sun does teach the need for injectable bone cements for osteoporotic vertebral compression fractures in the elderly (pg. 319 Col. 1 para. 1) and PMMA bone cement is known for use in augmenting and stabilizing fractured vertebral bodies (abstract). Accordingly, one of ordinary skill in the art at the time of filing of the claimed invention would have been motivated to modify the method of Sun to including additional known bone diseases or conditions in need of bone regeneration and treatment such as fractures and osteoporosis. One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification, since Sun reports that PMMA compositions are well known for their use in repairing bone.
With respect to claims 20 and 32, Sun teaches the composition further containing BMP-2, a osteogenic agent (abstract and pg. 320 Col. 1 para. 2).
With respect to claims 25 and 26, Sun teaches the PMMA-hydrogel hybrid loaded BMP-2 composition is injected into rabbit femoral bone-defect models biodegradable (is a composition and injected into a site where bone disease has progressed) (abstract, pg. 322-323 bridging para. and pg. 326 Col. 1 para. 1). With respect to claim 27, Sun teaches the composition enhances femur bone formation (cortical bone) (abstract).
None of Sun, Ho or Zhang teach the method where the composition is prepared by a method comprising mixing glycol chitosan and oxidized hyaluronate in weight ratio of 1 to 10:1 to obtain a hydrogel; and then mixing polymethyl methacrylate (PMMA) and a stem cell spheroid in the obtained hydrogel as recited in claim 28. However, Sa teaches a composition for use as a bone substitute where a chitosan hydrogel glycerophosphate hydrogel is added to PMMA to improve the performance of the PMMA and to create pores (abstract). In addition, Sa teaches mixing the formed hydrogel with the PMMA cement (pg. 91084 Section 2.3). In further support, Liu teaches a method of treating cartilage tissue defects by injecting a composition comprising a hydrogel composed of glycol chitosan and oxidized hyaluronic acid and BMSCs (bone marrow stem cells) (abstract and pg. S723 last para) and teaches the method by mixing the hydrogel with BMSCs (bone marrow stem cells) (pg. S723 Col.1-2 bridging para.). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method taught by the combined teachings of Sun, Ho or Zhang to combine the PMMA and stem cell spheroid with a formed chitosan hydrogel to improve the performance of the PMMA and form pores in the injectable composition as taught by Sa. It would have been obvious to one of ordinary skill in the art to first obtain the chitosan hydrogel and then add PMMA and the stem cell spheroids, since similar methods teach that it is possible to combine these ingredients after forming the gel as taught by Sa and Liu. One of ordinary skill in the art would have a reasonable expectation of success in modifying the method taught by the combined teachings of Sun, Ho or Zhang to combine the PMMA and stem cell spheroid with a formed chitosan hydrogel, since Sa teaches combining a chitosan hydrogel with PMMA and Liu teaches combining a chitosan hydrogel with cells after the hydrogel is obtained.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Dec. 25, 2025 have been fully considered but they are not persuasive. The majority the arguments are repeated from the previous Remarks filed on Sept. 9, 2024 and Apr. 28, 2025.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that Sun does not teach the method where the composition contains stem cell spheroids and Ho does not each the stem cells are any of those listed in claims 23 and 24 (Remarks p. 5 para. 5-6). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Sun is being relied upon for teaching of the administration of a composition containing PMMA and hydrogel (abstract), Ho is being relied upon for teaching administering mesenchymal stem cell (MSC) spheroids which have improved therapeutic potential in vitro compared with dissociated MSCs (pg. 773-774 bridging para. and pg. 773 significance), and Zhang is being relied upon for the teaching adding stem cells to a scaffold aids in bone repair. It is maintained, that one of ordinary skill in the art would have been motivated to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids for the known healing benefits of MSCs on bone repair as taught by Zhang and the improved therapeutic potential of the cells when cultured as spheroids as taught by Ho. Applicant addressed each prior art reference separately and only with regard to the specific limitations of that reference. However, when the prior art references are taken as a whole, they teach that the skilled artisan knows each step of the method as currently claimed.
Applicant argues that Sun does not teach the method where chitosan is glycerol chitosan, even though Liu teaches a method of treating cartilage defects with a composition containing a hydrogel composed of glycol chitosan and oxidized hyaluronic acid and BMSCs (Remarks pg. 5 para. 7). However, this argument was not found to be persuasive, since one of ordinary skill in the art would have been motivated to modify the method of Sun so that the chitosan is glycol chitosan for the benefit of having good solubility in water as taught by Liu as explained in the rejection.
Applicant argues that the ratio of hydrogel to PPMA is critical for the desired effects and to maintained the desired properties, is not a result effective variable, and Sun is silent with respect to the volume ratio of hydrogel to PPMA (Remarks pg. 6 para. 1). However, this argument was not found to be persuasive, since Sun teaches mixing the hydrogel and PMMA at different ratios, even though Sun is silent with respect to the volume ratio and clearly teaches that the ratio is a result effective variable. Sun reports that the transparency, the setting temperatures, compressive strength, the injectability and degradation rate of the hybrid cements depends on the ratio of PMMA and hydrogel (pg. 323 Col. 1 last para to Col. 2 para. 3). Furthermore, it is not clear what desired effects the Applicant is referring to and it is unclear exactly how the ratio is critical for the claimed invention.
Applicant argues that even though Ho teaches the use of mesenchymal stem cell (MSC) spheroids with ECM or RGD alginate gels for therapeutics, Ho does not teach the use of PMMA and there is no motivation to consider using PMMA (Remarks pg. 6 para. 3). As stated previously, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Sun is being relied upon for teaching of the administration of a composition containing PMMA and hydrogel (abstract), Ho is being relied upon for teaching administering mesenchymal stem cell (MSC) spheroids which have improved therapeutic potential in vitro compared with dissociated MSCs (pg. 773-774 bridging para. and pg. 773 significance), and Zhang is being relied upon for the teaching adding stem cells to a scaffold aids in bone repair. It is maintained, that one of ordinary skill in the art would have been motivated to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids for the known healing benefits of MSCs on bone repair as taught by Zhang and the improved therapeutic potential of the cells when cultured as spheroids as taught by Ho. Applicant addressed each prior art reference separately and only with regard to the specific limitations of that reference. However, when the prior art references are taken as a whole, they teach that the skilled artisan knows each step of the method as currently claimed.
Applicant argues that Lui doesn’t remedy the deficiencies of Sun, Ho and Zhang and only uses scaffold materials which are more hydrophilic than PMMA (Remarks pg. 6 para. 4). However, this argument was not found to be persuasive, since the arguments with respect to the rejections over Sun, Ho and Zhang were not found to be persuasive as explained above.
Applicant further argues that given the hydrophobic property of PMMA there has been no reported use of PMMA with stem cells or stem cell spheroids (Remarks pg. 6 last para. to pg. 7 para. 1). However, this argument was not found to be persuasive, since Applicant has not provided any evidence that stem cells cannot be encapsulated in PMMA or combined with PMMA in a scaffold. Attorney statements or arguments cannot take the place of evidence which must be supported by an appropriate affidavit or declaration (MPEP 716.01(c) II). Additionally, it is noted that Scharp et al. (US 2020/0315976 A1)(ref. of record) reports a method of treating a disease or disorder by administering stem cells which are enclosed in an encapsulating material including PMMA (0237).
Applicant argues that PMMA is not a good material to encapsulate stem cells since it provides a tight structure which would limit the oxygen supply to the cells (Remarks pg. 7 para. 2). In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., encapsulating the stem cell spheroids with PMMA) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, no evidence has been present demonstrating that PMMA is not a good material to encapsulate stem cells.
Applicant argues that Ho and Zhang teach away from using PMMA as a scaffold for encapsulating cells, since Zhang does not include PMMA as scaffold in combination with MSCs for osteogenesis (Remarks pg. 8 para. 3). However, this argument was not found to be persuasive, since not teaching a component of a composition is not a teaching away. Zhang and Ho do not explicitly state that PMMA cannot be used as a scaffold for MSCs for osteogenesis. Additionally, as stated above, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a scaffold for MSCs for osteogenesis) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that there is no evidence in Zhang to motivate one to combine PMMA scaffold with MSCs to arrive at the claimed invention (Remarks pg. 7 para. 3). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the motivation to include MSCs in the PMMA composition being administered in the method of promoting bone regeneration or treating a bone disease or condition of Sun is the known benefit MSCs have on bone repair which is taught by Zhang. Furthermore, it would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to combine the instant ingredients for their known benefit of repairing bone, as disclosed by the cited references above, since each is well known in the art for their claimed purpose.
Applicant argues that impermissible hindsight was used and the Examiner picked features from each cited reference to expand the rejection for motivation (Remarks pg. 7 last para.). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant further argues that the Examiner did not provide motivation to combine the features in the art and did not meet the Graham v. Deere test (Remarks pg. 8 para. 1-3). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, it is maintained, that one of ordinary skill in the art would have been motivated to modify the method of Sun so that the PMMA-hydrogel hybrid composition includes stem cell spheroids for the known healing benefits of MSCs on bone repair as taught by Zhang and the improved therapeutic potential of the cells when cultured as spheroids as taught by Ho.
Applicant argues that the claims provide a method for promoting bone regeneration or treating a bone disease or a bone-related condition using a certain ratio of ingredients which provides an unexpected advantage with significant improvement as shown in the Examples and Figures. Applicant argues that FIGs 6A-6F demonstrate having hydrogel and PMMA with certain ratios improves the expression levels of osteoblasts and osteocytes (Remarks pg. 8 para. 4). Applicant argues that FIGs 9A-9D demonstrate that bone is significantly increased in the PMMS treated group (PM gel with MSCs spheroids) compared to the PM gel group (PMMA and hydrogel) (Remarks pg. 8 last para. to pg. 9 para. 2). However, these arguments were not found to be persuasive, since the cited references make obvious the claimed method and the data is not commensurate in scope with the claims. FIGs 6A-6F show the expression levels of osteo-differentiation markers in stem cells spheroids which have been differentiated in culture (0094-0098 of published application) and are not the results of a method for promoting bone regeneration or treating a bone disease or a bone-related condition as recited in claim 17. Claim 17 does not require the differentiation of the stem cell spheroids. FIGs 9A-9D show pictures of bone injected with either PMMA, PM or PMMS after injury and suggesting that there is an increase of bone in the PMMS treated bone compared to the PM treated bone (0108-0110 of published application). From this one set of images is unclear if there is a significant difference in bone formation in the PMMS treated bone compared to the PM treated bone. In addition, the ratio of hydrogel:PMMA was 8:2 which is not within the claimed range of 3 to 5:1 (0108 of published application).
Applicant requests an interview if the application is not in condition for allowance. Given the time constraints placed on the examiner, it was not possible to grant the requested interview after full consideration of the response and preparation of the above office action. Further, Applicants' correspondence contains both a Response and a Conditional Request for an Interview and as such does not comply with Rule 1.4: "... each distinct subject, inquiry, or order should be contained in a separate letter to avoid confusion and delay in answering letters dealing with different subjects." If, upon receipt of this Office Action, applicants still desire an interview, one may be requested as set forth in 37 CFR §1.133 by calling the examiner of record.
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632