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
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.
Response to Amendments
Applicant’s response filed Jul. 23, 2026 have been received and entered into the case.
Priority
Upon review of the record of U.S. applications No. 16/136,894, and No. 62/561,105, it has been determined that the composition of claims 1-9 was first disclosed in the present application, filed on 05/25/2023. Therefore, the filing date of Application No. 18/323,667 will be used for prior art purposes for these claims.
Status of the Claims
Claims 1-22 are currently pending.
Claims 10-22 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-9 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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Acta Biomaterialia, 2016) (ref. of record) in view of Alsberg et al. (US 2017/0183629 A1, Jun. 29, 2017) (ref. of record).
With respect to claims 1 and 8, Huang teaches an engineered neocartilage composition containing rabbit articular cartilage-derived cells at passage 5 (P5), P6 and P7 (abstract, pg. 150 para. 1, pg. 151-152 bridging para.). With respect to claims 1 and 8, Huang teaches the neocartilage with a tensile Young’s modulus ranging from about 1.0 to 4.8 MPa (1,000-4,800 kPa) and an ultimate tensile strength (UTS) ranging from about 0.5-1.5 MPa (500-1,500 kPa) (Fig. 5 a and b).
Huang is silent with respect to the glycosaminoglycan (GAG) per dry weight (GAG/DW) and the total collagen per dry weight (Col/DW) and does not teach the composition with ≥2% GAG/DW and ≥1% Col/DW as recited in claim 1. However, Huang teaches the neocartilage with glycosaminoglycan (GAG) weight per wet weight ranging from 4 to 10% and collagen weight per wet weight ranging from about 1.6 to 2.5% and (Fig.4 a and b, and pg. 154 para. 2). One of ordinary skill in the art would reasonably predict that the dry weight percentages of GAG and collagen would be proportional and similar to the wet weight after the water is removed.
With respect to claims 2 and 9, Huang teaches the neocartilage is scaffold free (abstract and Fig. 1). With respect to claim 4, Huang teaches the rabbit articular cartilage-derived cells contain chondrocytes (abstract and pg. 151-152 bridging para.). With respect to claim 6, Huang teaches the composition where the cell have been subjected to aggregate rejuvenation and a self-assembling process (abstract, pg. 152 Col. 1 para. 2-3 and Col. 2 para. 2, and Fig. 1).
Huang does not teach the engineered neocartilage tissue composition where the cartilage cells are derived from human costal (rib) cartilage as recited in claims 1, 3 and 8 or where the cells are allogenic sourced cells as recited in claim 3.
However, Alsberg teaches a similar engineered neocartilage tissue composition where the cells are isolated directly from pre-existing cartilage tissue including costal cartilage (abstract and 0087). Alsberg teaches the chondrogenic cells or chondrocytes can be allogeneic and from humans (0088).
Accordingly, at the time of the claimed invention, one of ordinary skill in the art would have been motivated to modify the teachings of Huang in such a way that the source of the cartilage-derived cells are human costal or rib cartilage cells for the purpose forming an engineered neocartilage tissue composition. Furthermore, it would have been obvious to one skilled in the art to have further modified Huang such that source of cells are human costal cartilage-derived cells, since similar engineered neocartilage tissue compositions were known to contain such cells as taught by Alsberg. Such a modification merely involves the substitution of one known source of articular cartilage-derived cells for another for an engineered neocartilage tissue composition. Additionally, it is noted that the term “allogeneic” is relative and depends on the subject being administered the composition. Since the claims are not directed to a method of administration of the composition the term does not further limit the composition.
Huang does not teach that the rabbit articular cartilage-derived cells contain progenitor cells as recited in claim 5.
However, Alsberg teaches a similar engineered neocartilage tissue composition where the cells are isolated directly from pre-existing cartilage tissue including costal cartilage (abstract and 0087). Alsberg teaches the cells can be progenitor cells, immature chondrocytes or mature chondrocytes (0067).
Accordingly, at the time of the claimed invention, one of ordinary skill in the art would have been motivated to modify the teachings of Huang in such a way that the cells include progenitor cells for forming an engineered neocartilage tissue composition. Furthermore, it would have been obvious to one skilled in the art to have further modified Huang such that the cells include progenitor cells, since similar engineered neocartilage tissue compositions were known to contain such cells as taught by Alsberg. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in including progenitor cells in the engineered neocartilage tissue composition of Huang, since similar engineered neocartilage tissue compositions were known to include progenitor cells as taught by Alsberg.
Huang does not teach the composition with at least a second tissue composition stacked thereon as recited in claim 7.
However, Alsberg teaches an engineered neocartilage tissue composition including multilayers with other cell types (0110 and 0116). Alsberg teaches the multilayers can be used to help form different tissue constructs for different tissue implants (0116).
Accordingly, at the time of the claimed invention, one of ordinary skill in the art would have been motivated to modify the teachings of Huang in such a way that the engineered neocartilage tissue composition includes at least a second tissue composition stacked on the initial composition for the benefit of being able to form a multi-layered engineered neocartilage tissue composition that is suitable for the particular tissue implant as taught by Alsberg. Furthermore, it would have been obvious to one skilled in the art to have further modified Huang such that the engineered neocartilage tissue composition includes additional layered tissue compositions, since similar engineered neocartilage tissue compositions were known to have layers of additional tissues as taught by Alsberg. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in including additional tissue compositions stacked in the engineered neocartilage tissue composition of Huang, since similar engineered neocartilage tissue compositions were known to include additional layers of tissue compositions as taught by Alsberg.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Jul. 23, 2026 have been fully considered but they are not persuasive.
With respect to the priority to previous applications, Applicant argues that the claims have support in U.S. applications No. 16/136,894 (now US Pat. 11,696929 B2) and No. 62/561,105 (Remarks pg. 5-9). Although chondrocytes derived from humans and ribs are mentioned as a source of chondrocytes in Col. 8 lines 49-51 of US Pat. 11,696929 B2, there is no actual description of an engineered neocartilage tissue composition with the claimed properties containing human costal cartilage-derived cells where the composition comprises ≥2% glycosaminoglycan per dry weight (GAG/DW) and ≥1% total collagen per dry weight (Col/DW), and exhibits ≥50 kPa tensile Young's modulus and ≥10 kPa ultimate tensile strength (UTS). The support described by Applicant in the Remarks gives smaller ranges for GAG content, collagen content, Young's modulus and UTS.
For example, GAG is from 0.5-12.5% dry weight and the collagen is from 2.5-12.5% per dry weight, whereas the claim is broader and includes ≥2% GAG per dry weight and ≥1% total collagen per dry weight (Remarks point c.). Additionally, Fig. 7 is to neocartilage comprising human articular cartilage. Similarly, the support described by Applicant in the Remarks gives smaller ranges for the Young's modulus which is 100 kPa to 3,000 kPa and UTS which is 100 to 1,000 kPa, whereas the claim is broader and includes ≥50 kPa tensile Young's modulus and ≥10 kPa UTS. Additionally, Fig. 8 is to neocartilage comprising human articular cartilage.
These limitations seemed have been brought into this continuation in part application. For example, see para. 0026-0033 and Example 2 of published application. These paragraphs were not present in the parent application.
Claims directed solely to subject matter disclosed in the parent application receive the benefit of the parent's earlier filing date (under 35 U.S.C. 120, 121, 365(c), or 386(c)). However, claims directed to the new matter are only entitled to the actual filing date of the CIP application itself. See MPEP § 201.08
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that it would not have been obvious to modify the teachings of Huang to substitute the rabbit articular chondrocytes (ACs) for human costal chondrocytes (CCs), because it is well-known in the art that the cellular behavior and characteristics that affected engineered cartilage formation substantially vary based on species and cell type (Remarks pg. 10 para. 3-4). Specifically, Applicant points to Shulse-Tanzil, which they argue reports that there are differences in chondrocyte morphology, proliferation, extracellular matrix synthesis and cytoskeleton assembly between species, that animal-derived chondrocytes develop more F-actin fibers during culturing than human chondrocytes and that these interspecies differences chondrocytes should be considered (Remarks pg. 10-11 bridging para.). However, this argument was not found to be persuasive, since Alsberg teaches that engineered neocartilage tissue compositions can contain chondrogenic cells that can be obtained from various biological sources including human and animals such as rabbits (0088) and different cartilage tissues (0087). Specifically, Alsberg states:
“Chondrogenic cells may be allogeneic, autologous, or a combination thereof, and may be obtained from various biological sources. Biological sources may include, for example, both human and non-human organisms. Nonhuman organisms contemplated by the present invention include primates, livestock animals (e.g., sheep, pigs, cows, horses, donkeys), laboratory test animals (e.g., mice, hamsters, rabbits, rats, guinea pigs), domestic companion animals (e.g., dogs, cats), birds (e.g., chicken, geese, ducks, and other poultry birds, game birds, emus, ostriches), captive wild or tamed animals (e.g., foxes, kangaroos, dingoes), reptiles and fish.” (0088)
In addition Alsberg states:
“Chondrogenic cells may be isolated directly from pre-existing cartilage tissue such as hyaline cartilage, elastic cartilage, or fibrocartilage. More specifically, chondrogenic cells may be isolated from articular cartilage (from either weight-bearing or non-weightbearing joints), costal cartilage, nasal cartilage, auricular
cartilage, tracheal cartilage, epiglottic cartilage, thyroid cartilage, arytenoid cartilage, and/or cricoid cartilage. Alternatively, chondrogenic cells may be isolated from bone marrow or an established cell line.” (0087)
Additionally, Huang suggests that their engineered neocartilage tissue composition could be formed with chondrocytes from different species and for autologous therapies and that the allogeneic juvenile ACs were used for their promising translational potential (pg. 151 Col. 2 para. 2 and pg. 158 para. 1). It is noted that the Shulse-Tanzil reference cited was considered to the extent argued but will not appear to any issued patent since it was not submitted in a proper information disclosure statement. Furthermore, it is noted in the remarks addressing priority to the parent application, Applicant states “that human costal cartilage-derived cells” in the present application are a subset of “human cartilage cells” (Remarks pg. 5 Table point a.) and the CIP appears to based on the substitution of articular cartilage derived chondrocytes with costal derived chondrocytes.
Applicant argues species-related differences in proliferation and extracellular matrix synthesis are relevant in forming engineered tissue (Remarks pg. 11 para. 1). In support, Applicant argues that Kisiday, Benya and Dell’Accio teach that rabbit chondrocytes can undergo higher population doublings and can sufficiently redifferentiated to generate cartilaginous matrix compared to human chondrocytes (Remarks pg. 11 para. 2). Applicant further argues that Kisiday, Benya and Dell’Accio teach away from using human chondrocytes in the method of Huang which highly expands the cells, since the references report that human cells do not undergo high population doublings and do not sufficiently redifferentiate to generate cartilage (Remarks pg. 11 para. 2-3). However, these arguments were not found to be persuasive, for the same reasons given above, since Alsberg and Huang make obvious the substitution of chondrocyte species and cell tissue source. This is further supported by Alsberg’s teaching that engineered neocartilage tissue compositions can contain chondrogenic cells that can be obtained from various biological sources including human and animals such as rabbits (0088) and different cartilage tissues (0087). Additionally, Huang suggests that their engineered neocartilage tissue composition could be formed with chondrocytes from different species and for autologous therapies and that the allogeneic juvenile ACs were used for their promising translational potential (pg. 151 Col. 2 para. 2 and pg. 158 para. 1). It is noted that the references, Kisiday, Benya and Dell’Accio, cited in the Remarks were considered to the extent argued but will not appear to any issued patent since it was not submitted in a proper information disclosure statement.
Applicant argues that it would not be obvious to modify the articular chondrocytes in Huang to use costal chondrocytes, since costal cartilage cells have fundamentally different behavior and characteristics than articular chondrocytes in the context of cartilage tissue engineering (Remarks pg. 11-12 bridging para.). Applicant further argues that Lee teaches that ACs and CCs differ in expansion, redifferentiation and tissue formation. Specifically, Lee teaches that rabbit CCs expand 3-fold more than ACs up to passage 4; dedifferentiation to fibroblasts in culture is slower in ACs than CCs; and CCs contract collagen gel more than ACs (Remarks pg. 12 para. 1-4). According, Applicant argues that it would not be reasonably predicted that human CCs would generate tissue with the biochemical and mechanical properties achieved by Huang, because ACs and CCs exhibit different proliferation and redifferentiation kinetics and cartilage tissue formation capability and it is these properties that Huang relies on to generate neocartilage (Remarks pg. 13 para. 1). Additionally, Applicant argues based on the teaching in Lee that CCs exhibit rapid phenotypic loss, a skilled person would expect including the cells in Huang would have reduce success (Remarks pg. 13 para. 1). However, these arguments were not found to persuasive, since the combination of Huang and Alsberg make obvious the substitution of chondrocyte species and cell tissue source as stated above. This is further supported by Alsberg’s teaching that engineered neocartilage tissue compositions can contain chondrogenic cells that can be obtained from various biological sources including human and animals such as rabbits (0088) and different cartilage tissues (0087). Additionally, Huang suggests that their engineered neocartilage tissue composition could be formed with chondrocytes from different species and for autologous therapies and that the allogeneic juvenile ACs were used for their promising translational potential (pg. 151 Col. 2 para. 2 and pg. 158 para. 1). It is noted that the reference, Lee, cited in the Remarks was considered to the extent argued but will not appear to any issued patent since it was not submitted in a proper information disclosure statement.
Applicant argues that it would not have been obvious to substitute the rabbit chondrocytes taught by Huang with the human chondrocytes taught by Alsberg in light of the evidence present showing the differences between the cells (Remarks pg. 13 para. 2). Applicant further argues that hindsight reasoning was used to substitute the cells of Huang with those of Alsberg, since Huang optimizes their tissue engineering method for rabbit ACs, the substitution requires a change of species and cell source, and neither Huang nor Alsberg provide any teaching that the cells would behave similarly in Huang’s culture protocol or generate engineered neocartilage with the claimed properties and by changing the species and the cell source (Remarks pg. 13 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). It is maintained it would have been obvious to substitute the articular chondrocytes taught by Huang with additional known sources of chondrocytes including human costal chondrocytes used in neocartilage engineered tissue as taught by Alsberg.
Applicant further argues that the culture system of Alsberg is different from that of Huang and the biological processes occurring during tissue formation in Alsberg are not directly comparable, since Alsberg’s method requires aggregates of costal cartilage cells with microparticles/nanoparticles (Remarks pg. 14 para. 1-2). In addition, Applicant argues that Huang does not teach using additional components in their culture system and microparticles taught by Alsberg alter the cellular microenvironment by introducing cell-material interactions in addition to the cell-cell interaction present in Huang and result in different tissue formation from Huang. However, these arguments were not found to be persuasive, since Alsberg is not being relied upon for the engineered neocartilage tissue, but for additional sources of chondrocytes for such.
In summary, Applicant argues that neither Huang nor Alsberg investigate whether species and/or cell source impact cell expansion, redifferentiation and tissue formation in their protocols and do not demonstrate that human CCs have a similar response as rabbit ACs (Remarks pg. 14 last para.). Applicant argues that a person of ordinary skill in the art would not have reasonably expected that a protocol for using rabbit ACs could be used for human CC, since the cited references recognize that proliferation, dedifferentiation, redifferentiation and extracellular matrix synthesis is dependent on species and cell source (Remarks pg. 15 para. 1). These arguments were not found to persuasive, since both Huang and Alsberg suggest using other sources of chondrocytes for engineered neocartilage tissue compositions.
It is noted that Applicant request that the withdrawn claims should be rejoined if the claims of Group I are deemed allowable, since these claims include the limitations of Group I (Remarks pg. 15 para. 2), however the claims are not yet deemed allowable.
Applicant argues since claims 2-9 depend from claim 1, they are non-obvious for the same reasons (Remarks pg. 15 para. 3). However, this argument was not found to persuasive, since the arguments with respect to claim 1 were not found to be persuasive.
Conclusion
No claims are allowed.
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.
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
