DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-36 are pending, all of which have been considered on the merits.
Drawings
Black and white were submitted with the filing of this application (on 6/24/2019); however, the specification makes reference to color photographs (See as-filed specification at Pg. 8, ln 12-15).
The drawings are objected to because it is unclear if there are supposed to be color drawings present in the application file, and if so, there is not a petition for acceptance of color drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Examiner’s Comments
In claims 1 and 9, step (i) technically recites two active steps: thawing and administering, it would be preferred to recite each of these steps as separate active steps, i.e. step i) thawing the MDCs, and step j) administering the thawed MDCs to a bone suffering from the bone defect, disease or pathology of the mammalian subject.
In claims 21 and 29, each of the claims step (d) technically recites two active steps: isolating the MDCs and administering the isolated MDCs, it would be preferred to recite each of these steps as separate active steps, i.e. step d) isolating the skeletal-derived MDCs…, and step e) administering the MDCs to the bone….
Claim Objections
Claim 9 is objected to because of the following informality: the word "comprising" should be inserted after the preamble, i.e. "A method of augmenting bone mass or density in a mammalian subject comprising:..."
Appropriate correction is required.
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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 15, 16, 20, 35 and 36 are rejected under 35 USC 102(b) as being anticipated by Lee et al (J Cell Biol, 2000).
Lee et al disclose isolation of a cell population comprising muscle-derived cells (MDCs), as well as application of said MDCs for treatment of a bone defect.
Specifically, Lee et al report isolating muscle-derived cells (MDCs) from a mouse (a mammal) by suspending primary skeletal muscle cells in growth medium; pre-plating the primary cells in a first collagen-coated culture container; then after ~1 hour transferring the supernatant and non-adherent cells to a second collagen-coated culture container; the serial replating of the supernatant and non-adherent cells was repeated 5-6 times. After 5-6 platings the culture was enriched for 'slowly adhering MDCs' (pp6); these cells were harvested, clonally expanded, transfected with rhBMP-2, seeded onto a collagen sponge, and the rhBMP-2 transduced MDC-seeded sponge was transplanted into a full-thickness skull defect (See Lee et al, Pg. 1086- 1088 "Isolation of Muscle-derived Cells," "Clonal Isolation of Purified Muscle-derived Cells," "In Vivo Differentiation of Muscle-derived Cells in Myogenic and Osteogenic Lineages," and "Skull Defect Assay"). Lee et al reports the skull defects treated with rhBMP-2 transduced MDC-seeded sponges showed full healing (See Lee et al, Pg. 1093, "Enhancement of Bone Healing by Genetically Engineered mc13 Cells").
The method of Lee et al reads on the instant claims as follows:
The step of isolating primary cells from mouse skeletal muscle reads on the claimed step of 'isolating skeletal muscle cells from a mammal' (claim 15, step (a)), the step of suspending the cells in the first collagen-coated culture container for ~1 hour reads on the claimed step of 'suspending the mammalian skeletal muscle cells in a first cell culture container for between 30 and 120 minutes' (claim 15, step (b)). These steps also read on the claimed step of 'suspending cells isolated from mammalian skeletal muscle in a first cell culture container for a duration sufficient to adhere a first cell population to the container and to leave a second cell population unadhered and in a culture medium in the container' (claims 35 and 36, step (a)).
The step of transferring the supernatant and non-adhered cells through the serial plating to the sixth pre-plate reads on the claimed step of 'decanting the media and non-adherent cells from the first cell culture container to a second cell culture container' (claim 15, step (c)) as well as 'transferring the culture medium and second cell population from the first cell culture container to a second cell culture container' (claims 35 and 36, step (b)). Though Lee et al actually serially transfer the cells through six platings, the step of Lee et al still appropriately reads on the claimed method by considering the first collagen-coated plate as "the first cell culture container" and the sixth collagen-coated plate (pre-plate) as "the second cell culture container" (noting that the claims do not exclude additional transferring steps between 'the first' and 'the second cell culture containers').
The cell culture was maintained in the sixth pre-plate until 30-40% of the cells had adhered to the flask, thereby reading on the claimed step of 'allowing the remaining cells in the media to attach to the walls of the second cell culture container' (claim 15, step (d); claims 35 and 36, step (c)).
The step of clonally expanding the MDCs from pp6 necessarily involves isolation of individual cells from the sixth culture plate, the isolation reads on the claimed step of 'isolating the cells attached to the second cell culture container to obtain said cell population containing MDCs (claim 15, step (e); claims 35 and 36, step (d)). Clonal expansion of the cells further reads on the claimed step of 'culturing the MDCs to expand their number before administering to the bone' (claim 20).
The step of seeding the rhBMP-2 transduced MDCs onto collagen sponges and injecting the cell seeded sponges into the skull defects reads on the claimed step of 'administering the MDCs to a bone suffering from the bone defect of the mammalian subject' (claim 15, step (f); claim 35). A skull defect is a symptom of a bone defect, specifically a defect is considered to read on decreased bone density and decreased bone mass (claim 16). Because the implanted rhBMP-2 transduced MDCs did repair the skull defect, the administration of the cells did effectively treat the bone defect (claim 35) by increasing bone density and bone mass, thereby treating at least one symptom of the bone defect (claim 15).
Therefore the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 15-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al (J Cell Biol, 2000), in view of Chancellor et al (US Patent 6,866,842).
The teachings of Lee et al are set forth above. Lee et al has been shown to anticipate claims 15, 16 and 20.
Lee et al differs from the method of instant claims 17 and 18 in that Lee et al does not specifically inject the MDCs onto the surface of the bone or into the bone, per se, but rather provides the MDCs on a collagen sponge and places the collagen sponge into the skull defect. However, it is submitted that given the level of skill of the ordinary artisan (high, being that of accomplished surgeons, tissue engineers and cell biologists), the artisan of ordinary skill would have recognized that the exact placement of the MDCs in relation to the bone would depend on the bone site and the nature of the defect or disease. In the case of Lee et al, full thickness skull defects were being treated, thus it was most appropriate to employ a scaffold comprising said MDCs to aide in closure of the defect. However, in cases where the bone defect to be treated is a fracture or partial-thickness void, it would have been prima facie obvious to the artisan to administer the MDCs to the disunion site of a fracture (i.e. inject the MDCs onto the disjoined bone surfaces) (claim 17), or inject the MDCs into the void (i.e. inject the MDCs into the interior of the bone) (claim 18). Therefore, though Lee et al does not specifically teach the limitations of instant claims 17 and 18 it is submitted that the artisan of ordinary skill in the art at the time the invention was made would have found it prima facie obvious to modify the administration protocol so as to suit the particular situation of bone disease or defect, and would have found the methods of instant claims 17 and 18 obvious.
Lee et al differs from the method of instant claim 19 in that Lee et al teach treatment of mouse skull defects, not human. However, Chancellor et al is relied upon to support that the same protocol disclosed by Lee et al was contemplated for use with human MDCs for treatment of human bone defects (See Chancellor et al, col. 1, ln 17-20 & col. 20, ln 11-20). Chancellor et al provides an enabling disclosure for the same protocol for enrichment of MDCs from skeletal muscle tissue via serial plating as is taught by Lee et al (See Chancellor et al, e.g., claim 7); because the patented method of Chancellor et al encompasses humans, Chancellor et al supports that enrichment of MDCs via the method of Lee et al is also possible on humans, thus one having ordinary skill in the art would have had a reasonable expectation of successfully carrying out the protocol of Lee et al using human subjects (claim 19).
Claims 21, 27-30 and 34 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al (J Cell Biol, 2000).
The teachings of Lee et al have been set forth above. The method of Lee et al is considered to be comparable to the method of instant claims 21 and 29 as follows:
The step of isolating primary cells from mouse skeletal muscle and suspending the cells in the first collagen-coated culture container reads on the claimed step of 'plating a suspension of skeletal muscle cells from mammalian skeletal muscle tissue into a first container to which fibroblast cells of the skeletal muscle cell suspension adhere' (claims 21 and 29, step (a)).
The steps of transferring the supernatant and non-adhered cells to a second collagen-coated culture container once the cells reach 30-40% confluence is comparable to the claimed step 're-plating non-adherent cells from step (a) in a second container,' (claims 21 and 29, step (b)). The serial replating through six total platings is comparable to claimed step (c) of claims 21 and 29.
The step of clonally expanding the MDCs from pp6 necessarily involves isolation of individual cells from the sixth culture plate, the isolation reads on the claimed step of 'isolating the skeletal muscle-derived MDCs' (claims 21 and 29, step (d)). Clonal expansion of the cells further reads on the claimed step of 'culturing the MDCs to expand their number before administering to the bone' (claim 34).
The step of seeding the rhBMP-2 transduced MDCs onto collagen sponges and injecting the cell seeded sponges into the skull defects reads on the claimed step of 'administering the MDCs to a bone suffering from the bone defect' (claims 21 & 29). A hole in the skull is an example of a decrease in bone density and mass, which is a symptom of a bone defect (claim 30). The skull defect was created by burring a hole in the skull, such burring is considered 'a bone fracture caused by trauma' (claims 27 and 28). Because the implanted rhBMP-2 transduced MDCs did repair the skull defect, the administration of the cells did effectively treat the bone defect (claim 21) by increasing bone density and bone mass, thereby treating at least one symptom of the bone defect (claim 29).
Finally, because the MDCs administered to the bone defect did show osteogenic potential (by regenerating bone), the MDCs isolated and administered by Lee et al are appropriately considered to be osteogenic lineage cells.
The method of Lee et al differs from instant claims 21 and 29 in that Lee et al reports transferring the culture medium and non-adherent cells after 30-40% of the cells had adhered to the container, whereas the instant claims require the transfer to occur after only 15-20% of the cells had adhered. It is submitted that one having ordinary skill in the art at the time the invention was made would understand that the waiting time in between transfers is directly related to the threshold proportion of adherent cells which must be adhered (i.e. if one waits for 30-40% of the adherent cells to adhere before transferring the supernatant, one will be waiting longer than if one were only waiting for 10% of the adherent cells to adhere before transferring the supernatant). Therefore, performing the serial transfer when a lesser proportion of adherence cells had adhered would hasten the method. Furthermore, because the cells of interest (the MDCs) are non-adherent, there is no risk that MDCs will be lost by performing the serial transfers at shorter intervals. Because speeding up a method (with no risk of loss of desired product) is always desirable (time being money), one would have been motivated to perform each transfer of Lee et al when less than 30-40% of the cells were adhered, for example when only 15-20% of the cells were adhered. One would have had a reasonable expectation that the MDCs could still successfully be enriched for in the shortened method because MDCs are not adherent, thus they would not be lost by performing the transfers with lower percentages of adherent cells. Therefore the method of claims 21, 27-29 and 34 are held to have been prima facie obvious.
Claims 21-34 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al (J Cell Biol, 2000), in view of Chancellor et al (US Patent 6,866,842).
The teachings of Lee et al are set forth above. Lee et al has been shown to render obvious the subject matter of claims 21, 27-30 and 34.
Lee et al differs from the method of instant claims 25, 26, 31 and 32 in that Lee et al does not specifically inject the MDCs onto the surface of the bone or into the bone, per se, but rather provides the MDCs on a collagen sponge and places the collagen sponge into the skull defect. However, it is submitted that given the level of skill of the ordinary artisan (high, being that of accomplished surgeons, tissue engineers and cell biologists), the artisan of ordinary skill would have recognized that the exact placement of the MDCs in relation to the bone would depend on the bone site and the nature of the defect or disease. In the case of Lee et al, full thickness skull defects were being treated, thus it was most appropriate to employ a scaffold comprising said MDCs to aide in closure of the defect. However, in cases where the bone defect to be treated is a fracture or partial-thickness void, it would have been prima facie obvious to the artisan to administer the MDCs to the disunion site of a fracture (i.e. inject the MDCs onto the disjoined bone surfaces) (claims 25 and 31), or inject the MDCs into the void (i.e. inject the MDCs into the interior of the bone) (claims 26 and 23). Therefore, though Lee et al does not specifically teach the limitations of instant claims 25, 26, 31, 32, 50 and 51 it is submitted that the artisan of ordinary skill in the art at the time the invention was made would have found it prima facie obvious to modify the administration protocol so as to suit the particular situation of bone disease or defect, and would have found the methods of instant claims 25, 26, 31 and 32 obvious.
Lee et al differs from the method of instant claims 22 and 33 in that Lee et al teach treatment of mouse skull defects, not human. However, Chancellor et al is relied upon to support that the same protocol disclosed by Lee et al was contemplated for use with human MDCs for treatment of human bone defects (See Chancellor et al, col. 1, ln 17-20 & col. 20, ln 11-20). Chancellor et al provides an enabling disclosure for the same protocol for enrichment of MDCs from skeletal muscle tissue via serial plating as is taught by Lee et al (See Chancellor et al, e.g., claim 7); because the patented method of Chancellor et al encompasses humans, Chancellor et al supports that enrichment of MDCs via the method of Lee et al is also possible on humans, thus one having ordinary skill in the art would have had a reasonable expectation of successfully carrying out the protocol of Lee et al using human subjects (claims 22 and 33).
Vilquin et al is further relied upon to support that human skeletal muscle cells harvested and intended for genetic modification and readministration as part of cellular therapy can be harvested from healthy or diseased individuals (See Vilquin et al, ¶0127); thus one having ordinary skill in the art would have had a reasonable expectation of successfully carrying out the method of Lee et al on human patients when the cells had been harvested either prior to, or after, onset of the disease or defect being treated (claims 23 and 24). It is particularly noted that in cases of bone defects due to physical trauma (i.e. fractures), the onset of the 'disease/defect' would not affect the cells of unrelated skeletal muscle, thus one would not have had any expectation of different results using skeletal muscle tissue obtained before or after a fracture.
Claims 1-14 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al (J Cell Biol, 2000), in view of Chancellor et al (US Patent 6,866,842) and Vilquin et al (US 2004/0043008).
The teachings of Lee et al have been set forth above. The method of Lee et al is considered to be comparable to the method of instant claims 1 and 9 as follows:
The step of isolating primary cells from mouse skeletal muscle reads on the claimed step of 'isolating skeletal muscle cells from a mammal' (claims 1 and 9, step (a)), the step of suspending the cells in the first collagen-coated culture container for ~1 hour reads on the claimed step of 'suspending the mammalian skeletal muscle cells in a first cell culture container for between 30 and 120 minutes' (claims 1 and 9, step (c)).
The step of transferring the supernatant and non-adhered cells through the serial plating to the sixth pre-plate reads on the claimed step of 'decanting the media and non-adherent cells from the first cell culture container to a second cell culture container' (claims 1 and 9, step (d)). As discussed above, though Lee et al actually serially transfer the cells through six platings, the step of Lee et al still appropriately reads on the claimed method by considering the first collagen-coated plate as "the first cell culture container" and the sixth collagen-coated plate (pre-plate) as "the second cell culture container" (noting that the claims do not exclude additional transferring steps between 'the first' and 'the second cell culture containers').
The cell culture was maintained in the sixth pre-plate until 30-40% of the cells had adhered to the flask, thereby reading on the claimed step of 'allowing the remaining cells in the media to attach to the walls of the second cell culture container' (claims 1 and 9, step (e)).
The step of clonally expanding the MDCs from pp6 necessarily involves isolation of individual cells from the sixth culture plate, the isolation reads on the claimed step of 'isolating the cells from the walls of the second cell culture container' (claims 1 and 9, step (f)). Clonal expansion of the cells further reads on the claimed step of 'culturing cells to expand their number' (claims 1 and 9, step (g)).
The step of seeding the rhBMP-2 transduced MDCs onto collagen sponges and injecting the cell seeded sponges into the skull defects reads on the claimed step of 'administering the MDCs to a bone suffering from the bone defect of the mammalian subject' (claims 1, 7 and 9). The skull defect was created by burring a hole in the skull, such burring is considered 'a bone fracture caused by trauma' (claims 7 and 8). A skull defect is also considered to read on decreased bone density and decreased bone mass (claim 9). Because the implanted rhBMP-2 transduced MDCs did repair the skull defect, the administration of the cells did effectively treat the bone defect (claim 1) by increasing bone density and bone mass (claim 9). Because full-thickness skull defects were recognized as untreatable, full closure is considered to read on increasing the density to greater than an average bone density (for a full thickness skull defect) in the patient (claim 14).
Finally, because the MDCs administered to the bone defect did show osteogenic potential (by regenerating bone), the MDCs isolated and administered by Lee et al are appropriately considered to be osteogenic lineage cells.
The method of Lee et al differs from the method of claims 1 and 9 in that Lee et al does not teach cooling the isolated skeletal muscle cells to a temperature lower than 10oC and storing the cells for 1-7 days prior to initiating culture, nor does Lee et al teach freezing the isolated MDCs to a temperature below 30oC and then thawing the cells prior to administration.
However, it is submitted that modification of the method of Lee et al to include such temperature changes would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made.
Regarding the initial cooling of the isolated cells prior to initiation of suspension, it is submitted that Vilquin et al teach that biopsied tissues (particularly human skeletal muscle tissue) can be maintained on ice (at 4oC) for up to 90 hours post harvest and prior to culture without having any appreciable effect on the tissue (See Vilquin et al, ¶0125). Such a cooling step would be recognized as necessary if transport was required from the site of initial harvest to the site of culture.
Regarding the freezing step after isolation of the MDCs, again Vilquin et al is referenced to evidence that cells isolated from skeletal muscle tissue can be cryopreserved and stored in liquid nitrogen (-190oC) and then thawed prior to use without detriment (See Vilquin et al, ¶0173-176). Vilquin et al express that storage of the cells is often desirable in order to permit use of the cells over a period of time.
Therefore, it is submitted that one having ordinary skill in the art would have found it prima facie obvious to modify the method of Lee et al to include a step of cooling the isolated skeletal muscle cells prior to initiating culture in order to preserve the tissue during transport from the surgical facility to the laboratory, thereby rendering obvious the claimed step of 'cooling the cells to a temperature lower than 10oC and storing the cells for 1-7 days' (claims 1 and 9, step (b)). As well as cryogenically storing the isolated MDCs in liquid nitrogen (-190oC) until needed, and when needed, then thawing the cells in a warm water bath, thereby rendering obvious the claimed steps of 'freezing the MDCs to a temperature below -30oC; and thawing the MDCs' (claims 1 and 9, steps (h) and (i)).
Lee et al further differs from the method of instant claims 5, 6, 12 and 13 in that Lee et al does not specifically inject the MDCs onto the surface of the bone or into the bone, per se, but rather provides the MDCs on a collagen sponge and places the collagen sponge into the skull defect. However, it is submitted that given the level of skill of the ordinary artisan (high, being that of accomplished surgeons, tissue engineers and cell biologists), the artisan of ordinary skill would have recognized that the exact placement of the MDCs in relation to the bone would depend on the bone site and the nature of the defect or disease. In the case of Lee et al, full thickness skull defects were being treated, thus it was most appropriate to employ a scaffold comprising said MDCs to aide in closure of the defect. However, in cases where the bone defect to be treated is a fracture or partial-thickness void, it would have been prima facie obvious to the artisan to administer the MDCs to the disunion site of a fracture (i.e. inject the MDCs onto the disjoined bone surfaces) (claims 5 and 12), or inject the MDCs into the void (i.e. inject the MDCs into the interior of the bone) (claims 6 and 13). Therefore, though Lee et al does not specifically teach the limitations of instant claims 5, 6, 12 and 13 it is submitted that the artisan of ordinary skill in the art at the time the invention was made would have found it prima facie obvious to modify the administration protocol so as to suit the particular situation of bone disease or defect, and would have found the methods of instant claims 25, 26, 31 and 32 obvious.
Lee et al differs from the method of instant claims 2 and 10 in that Lee et al teach treatment of mouse skull defects, not human. However, Chancellor et al is relied upon to support that the same protocol disclosed by Lee et al was contemplated for use with human MDCs for treatment of human bone defects (See Chancellor et al, col. 1, ln 17-20 & col. 20, ln 11-20). Chancellor et al provides an enabling disclosure for the same protocol for enrichment of MDCs from skeletal muscle tissue via serial plating as is taught by Lee et al (See Chancellor et al, e.g., claim 7); because the patented method of Chancellor et al encompasses humans, Chancellor et al supports that enrichment of MDCs via the method of Lee et al is also possible on humans, thus one having ordinary skill in the art would have had a reasonable expectation of successfully carrying out the protocol of Lee et al using human subjects (claims 2, 10).
Finally, Vilquin et al is further relied upon to support that human skeletal muscle cells harvested and intended for genetic modification and readministration as part of cellular therapy can be harvested from healthy or diseased individuals (See Vilquin et al, ¶0127); thus one having ordinary skill in the art would have had a reasonable expectation of successfully carrying out the method of Lee et al on human patients when the cells had been harvested either prior to, or after, onset of the disease or defect being treated (claims 3 and 4). It is particularly noted that in cases of bone defects due to physical trauma (i.e. fractures), the onset of the 'disease/defect' would not affect the cells of unrelated skeletal muscle, thus one would not have had any expectation of different results using skeletal muscle tissue obtained before or after a fracture.
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-35 are rejected under 35 U.S.C. 112, second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01.
The omitted steps are: a step of culturing the isolated MDCs under conditions effective to induce osteogenic differentiation of the MDCs.
Each of the independent claims are intended to treat a bone defect, disease or pathology, augment bone mass or density, or treat a symptom of a bone defect, disease or pathology, or require preparation of a cell which is capable of treating a bone defect, disease or pathology. Thus, each of the methods require a cell which promotes bone formation.
The claimed methods provide for isolation of MDCs; however, MDCs do not inherently promote bone formation, rather the MDCs must be stimulated or otherwise induced towards the osteogenic lineage such that they become osteogenic cells. The specification is enabling for methods of effecting MDCs to differentiate into osteogenic cells (i.e. stimulation of mouse MDCs with rhBMP-2; culture of human MDCs in cell pellets in osteogenic medium), yet the claims must recite such an effecting step, otherwise there is a gap between the step of providing the MDC and the step of treating the bone defect, disease or pathology, or augmenting the bone density or mass, or treating a symptom associated with a bone defect, disease or pathology.
According to Example 3 in the specification mouse MDCs isolated by the "Pre-Plating Technique" must be stimulated with rhBMP-2 in order to develop osteogenic characteristics (i.e. expression of osteocalcin and alkaline phosphatase, loss of expression of desmin), if not, the recovered MDCs develop myogenic characteristics (expression of desmin, become multinucleated and fuse to form myotubes) (See Specification Pg. 31). Therefore mouse MDCs must be treated with rhBMP-2 in order to differentiate towards the osteogenic lineage and be useful in methods of treating bone defects (as myogenic cells are not useful in treating bone defects).
According to Example 2 in the specification slowly adhering mouse cells isolated from the second cell culture container in the "Single Plating Method" are characterized as being of myogenic lineage, fibroblasts, hematopoietic lineage, or endothelial cells, no mention is made of recovered slowly adhering cells being of osteogenic lineage. In Example 4, human MDCs isolated by the "Single Plating Method" are only shown to have osteogenic characteristics after culture in cell pellets in osteogenic medium. Therefore, it appears that mouse and human MDCs, even when produced via the "Single Plating Method" still require further treatment in order to have the osteogenic potential.
Non-Statutory 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-4, 7-11, 14-16, 19-24, 27-30 and 33-36 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 9,199,003.
Although the claims are not identical, they are not patentably distinct for the following reasons:
Regarding instant claim 36: Claim 1 of US Patent 9199003 recites the isolation method of instant claim 36, that is, patented claim 1 teaches steps which anticipates steps (a)-(d) of claim 36. Patent claim 1 teaches using the MDCs to repair calvarial defects (which are bone defects), thus patented claim 1 anticipates instant claim 36.
Regarding instant claims 15, 16, and 21: Claim 1 of US Patent 9199003 anticipates instant claims 15, 16 and 21, specifically patent step (a) reads on claim steps (a)-(e) and patent steps (b)-(d) read on instant claim step (f).
Regarding instant claims 21, 27, 29, and 30: The patented claims differ from the instant claims in that the patented claims define the time period for culture in the first container based on time, as opposed to adherence %. However, it is submitted the adherence % recited in the instant claims would inherently be met by carrying out the method of the patented claims. As such, the patented claims are considered to anticipate instant claims 21, 22, 27, 29, 30 and 33, as well.
Regarding instant claims 20 and 34: Patent claim 4 states the MDCs are cultured on the SIS to expand their number prior to being implanted.
Regarding instant claims 1, 7, 9, and 14: Claim 1 of US Patent 9199003, instant claims 1 and 9 are similar to instant claim 15, except instant claims 1 and 9 require an additional step of freezing and thawing the skeletal muscle cells from the biopsy prior to beginning the isolation technique. Though the patented claims do not recite such an initial step, such is considered to have been prima facie obvious to one having ordinary skill in the art, at the time the invention was made, if the biopsy sample could not be worked on immediately. Cooling of cells prior to use is routine in the art in order to preserve cells for later periods of work.
Regarding instant claims 3, 4, 23 and 24: Use of autologous cell is the gold standard, however, allogenic cells are second best. Use of MDCs from either the subject being treated or an allogenic tissue donor would have bene prima facie obvious over the method of the patented claim.
Regarding instant claims 8, 11 and 28: The etiology of the calvarial defect does not distinguish the patented method from the instant claimed method. Treatment of a calvarial defect due to any cause would have been prima facie obvious.
Regarding claims 2, 10, 19, 22, 33: Use of human cells to treat human patients is considered prima facie obvious, as human medicine is a goal in modern medicine.
Claims 1-36 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 7-10 of U.S. Patent No. 8,211,423, in view of Chancellor et al (US Patent 7,115,714).
Although the claims are not identical, they are not patentably distinct for the following reasons:
Regarding instant claim 36: Claim 7 of US Patent 8,211,423 recites the isolation method of instant claim 36, that is, patented claim 7 teaches steps which anticipates steps (a)-(d) of claim 36. Patented claim 7 differs only with regards to the fact the preamble does not state the end population of MDCs are useful for administration to treat a bone defect. However, this is an intended use limitation, only. MPEP 2111.02 states that when the preamble only contains statements of intended use, rather than any distinct definition of any of the claim elements or steps, then the preamble is not considered a limitation. Therefore patented claim 7 anticipates instant claim 36.
Regarding instant claims 15, 21, 29 and 35: As discussed above, claim 7 of US Patent 8,211,423 recites the isolation method of instant claims 15, 19, 21, 29 and 35, that is, patented claim 7 teaches steps (a)-(d) of instant claims 15, 21, 29 and 35. Patented claim 7 differs in that it does not teach administration of the MDCs for treatment of bone defects. However, use of MDCs for treatment of bone defects was known in the art, see US Patent 7,115,714 to Chancellor et al at Example 9. In order to use MDCs for treatment of bone defects Chancellor et al teach culturing isolated MDCs with rhBMP-2 in order to induce osteogenic differentiation (See Chancellor et al, col. 24, ln 30-53).
Therefore, given that Chancellor (US Patent 7115714) recognizes a need for treatment of bone defects, and discloses the means to do so using MDCs by first differentiating the MDCs into osteogenic cells, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made, to have isolated the MDCs via the method of patented claim 7, and then further culture the MDCs under conditions effective to induce differentiation to the osteogenic lineage so that the cells may then be used in repair of bone defects.
Regarding instant claims 16-20, 22-28 and 30-34: Following the discussion above, the method of Chancellor et al (US Patent 7115714) is intended for treatment of humans, thus use of the MDCs for treatment of bone defects in humans would have been prima facie obvious. With regards to the location on/in the bone for the administration, such would have been a matter of routine optimization.
Regarding claims 1-14: instant claims 1-14 are similar to claims 21-28, except claims 1-14 require an additional step of freezing and thawing the skeletal muscle cells from the biopsy prior to beginning the isolation technique. Though the patented claims do not recite such an initial step, such is considered to have been prima facie obvious to one having ordinary skill in the art, at the time the invention was made, if the biopsy sample could not be worked on immediately. Cooling of cells prior to use is routine in the art in order to preserve cells for later periods of work. With regards to the location on/in the bone for the administration, such would have been a matter of routine optimization. For the reasons discussed above, the additional differences between claims 1-14 and patented claims 7-10 are further held to have been obvious.
Claims 1-36 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 2-10 of co-pending application 19/054565, in view of Chancellor et al (US Patent 7,115,714).
Although the claims are not identical, they are not patentably distinct for the following reasons:
Regarding instant claim 36: When viewed as a whole, co-pending claims 2-10 render obvious the isolation method of instant claim 36, all limitations are taught throughout the claim set, though not in a single claim.
Regarding instant claims 15, 21, 29 and 35: As discussed above, copending claims 2-10 render obvious the isolation method of instant claims 15, 19, 21, 29 and 35, that is, patented claim 7 teaches steps (a)-(d) of instant claims 15, 21, 29 and 35. Copending claims 2-10 differ in that they does not teach administration of the MDCs for treatment of bone defects. However, use of MDCs for treatment of bone defects was known in the art, see US Patent 7,115,714 to Chancellor et al at Example 9. In order to use MDCs for treatment of bone defects Chancellor et al teach culturing isolated MDCs with rhBMP-2 in order to induce osteogenic differentiation (See Chancellor et al, col. 24, ln 30-53).
Therefore, given that Chancellor (US Patent 7115714) recognizes a need for treatment of bone defects, and discloses the means to do so using MDCs by first differentiating the MDCs into osteogenic cells, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made, to have isolated the MDCs via the method of copending claims 2-10, and then further culture the MDCs under conditions effective to induce differentiation to the osteogenic lineage so that the cells may then be used in repair of bone defects.
The copending claims do not teach the specific culture duration period of instant claim 15 step (c), or the percentages of adhered cells in instant claim 21 and 29, step (b), but these details are considered prima facie obvious, as the co-pending claim method results in the same MDCs.
Regarding instant claims 16-20, 22-28 and 30-34: Following the discussion above, the method of Chancellor et al (US Patent 7115714) is intended for treatment of humans, thus use of the MDCs for treatment of bone defects in humans would have been prima facie obvious. With regards to the location on/in the bone for the administration, such would have been a matter of routine optimization.
Regarding claims 1-14: instant claims 1-14 are similar to claims 21-28, except claims 1-14 require an additional step of freezing and thawing the skeletal muscle cells from the biopsy prior to beginning the isolation technique. Co-pending claims 2-4 recites a step of storing the skeletal muscle cells in cooler conditions, prior to the isolation protocol. Methods of storing cells after isolation were routine the art. With regards to the location on/in the bone for the administration, such would have been a matter of routine optimization.
This is a provisional rejection as the co-pending claims have not yet been patented.
Conclusion
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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