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
Applicant’s response filed September 29, 2025, has been considered. Rejections and/or objections not reiterated from the previous office action mailed July 7, 2025, are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The amended claims filed on September 29, 2025, have been acknowledged. Claims 2, 5, and 7-13 were cancelled. Claims 1, 3-4. 6, and 14-15 were amended. Claims 1, 3-4. 6, and 14-15 are pending and examined on the merits.
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d).The applicant claims foreign priority from CN201910100503.9 filed on January 31, 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, received August 02, 2021 and a certified translation received on February 3, 3025. Claims 1, 3-4. 6, and 14-15 find support in foreign application CN201910100503.9 filed on January 31, 2019.
Oath/Declaration
Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed by Dr. Dai Kai on September 29, 2025, has been considered but is insufficient to change the claim interpretation of instant claim 1 as set forth in the current Office action for the following reasons:
Although the Declaration positively recites the structures of the bone implant as recited in amended claim 1, (gelatin, compact bone, trabecular bone, blood vessel, and bone marrow), claim 1 still comprises two products, the gelatin sponge and active substance and the resulting bone implant. As there are still two possible products, the Declaration fails to change the Examiner’s claim interpretation.
Claim Interpretation
Claims 1 and 3-4 are product claims with two interpretations for the product.
The first interpretation is that the product is the biomaterial and the active substance. Under this interpretation, the biomaterial and the active substance are the only structural components. Claim 1 follows this interpretive path as it partially focuses on the biomaterial and the active substance.
The second interpretation is that the product is the bone implant created by the body after implantation. Under this interpretation, the only structural component is the bone implant containing gelatin, compact bone, trabecular bone, blood vessel, and bone marrow. Under this interpretation, the claim is not directed to the implanted material but to the resulting product created by the body.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 recites “taking the bone out for 3 weeks” but should read “taking the bone out after 3 weeks”.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112(b)
The prior rejection of claims 1, 3-7, and 11-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendments to claims 1 and 6 to recite “a gelatin sponge carrying only an active substance”, amendments to claim 1 to recite bone implant instead of stem cell generator and organoid, and amendments to claim 3 to remove the term pluripotent stem cells.
New Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant recites the limitation “wherein the bone marrow contains a stem cell and the stem cell is hematopoietic stem cell and mesenchymal stem cell.” As the claim references “a stem cell”, this is considered to refer to a single stem cell while Applicant recites two possible stem cell types, hematopoietic and mesenchymal. However, a stem cell cannot both be a hematopoietic and mesenchymal stem cell as these are distinct cell types. It is not clear whether Applicant meant for the claim to recite or instead of and between the two cell types or if Applicant wants the bone marrow to comprise hematopoietic and mesenchymal stem cells. If Applicant wants the stem cell to be one type of cell, Applicant can amend the claim to recite or. If Applicant wants bone marrow to comprise both cell types, Applicant can amend the claim to recite wherein the bone marrow comprises hematopoietic stem cells and mesenchymal stem cells.
Withdrawn Claim Rejections - 35 USC § 112(d)
The prior rejection of claims 5 and 11-12 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of Applicant’s cancellation of claims 5 and 11-12.
Withdrawn Claim Rejections - 35 USC § 101
The prior rejection of claims 1, 3-5 and 11-12 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter is withdrawn in light of Applicant’s amendments to claim 1 to recite bone implant instead of stem cell generator.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 1, 4-5, and 11-12 under 35 U.S.C. 102(a)(1) as being anticipated by Wikipedia (Human Embryonic Development. 2018) is withdrawn in light of Applicant’s amendments to claim 1 to recite bone implant instead of stem cell generator.
The prior rejection of claims 1, 3-5, and 11-12 under 35 U.S.C. 102(a)(1) as being anticipated by Kusumoto et al. (British Journal of Plastic Surgery 51: 275-280. 1998) is withdrawn in light of Applicant’s amendments to claim 1 to recite that implanting a gelatin sponge and the cancellation of claims 5 and 11-12.
The prior rejection of claims 6-7 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Kusumoto et al. (British Journal of Plastic Surgery 51: 275-280. 1998) is withdrawn in light of Applicant’s amendments to claim 6 and 13 to recite that implanting a gelatin sponge and the cancellation of claim 7.
New Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Clin Orthop Relat Res (2010) 468:1978–1985). This is a new rejection made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Under the first interpretation wherein the product is the gelatin and the active substance, Li teaches that they generated macroporous gelatin microspheres and loaded them with BMP-2. As applicant does not define a gelatin sponge, the macroporous gelatin microspheres are considered to also be a sponge as both are porous compounds. Li teaches that 500 mg gelatin microparticles were swollen at room temperature in 1 mL buffer solution of PBS solution and bovine serum albumin (BSA) (PBS/BSA [0.1%]) containing 1 mg rhBMP-2. This solution volume is below the microsphere’s theoretical swelling volume, which thus allowed complete growth factor adsorption (page 1979, column 1, paragraph 2-column 2, paragraph 3). Therefore, the mass ratio of the BMP-2 to the gelatin would be 1:500 (or 0.002:1).
Claims 1 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamamoto et al. (Biomaterials 56: 18-25. 2015). This is a new rejection made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Regarding claim 1, under the second interpretation wherein the product is the bone implant created by the body 3 weeks after implantation, claim 1 is interpreted as a product-by-process claim. As such, only the positively recited structures of the bone implant are considered germane to the patentability of the device. The recited structures of the bone implant are considered:
Gelatin
Compact bone (also known as cortical bone)
Trabecular bone
Blood vessel
Bone marrow
The recitation of a process limitation in claim 1 is not viewed as positively limiting the claimed product absent a showing that the process of making recited in claim 1 (i.e. implanting gelatin containing only an active substance) imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the organoid was produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Yamamoto teaches that they prepared gelatin sponges and loaded them with BMP-2 and inoculated the sponges with autologous bone marrow and implanted the sponge in an ulnar defect of a non-irradiated mouse for 6 weeks before assessing the resulting bone regeneration. The radius-ulna complex containing the defect was removed and fixed in 10 wt% neutral phosphate-buffered formalin solution to assess bone regeneration (page 19, column 1, paragraph 5-column 2, paragraph 5). Yamamoto teaches that new bone regeneration at the ulna defect occurred with trabecular and cortical bone regeneration occurring when combining bone marrow cells with BMP-2-releasing sponges. Yamamoto teaches that new bone regeneration was found in the entire area of the ulnar defect without the X-ray irradiation. Yamamoto teaches that X-ray irradiation causes poor cellularity and vascularity of the X-ray-irradiated bone tissue due to the degeneration of cells, including stem cells and progenitor cells in bone marrow, osteoblasts in bone, and endothelial cells in blood vessel walls, leading to impair bone regeneration. Yamamoto teaches that the BMP-BM group displayed a significant increase in trabecular number (TbN), trabecular area (TbA), and cortical area (CoA), and decrease in trabecular spacing (Tb.Sp), indicating that both trabecular and cortical bones were regenerated by combining bone marrow cells with BMP-2-releasing sponges. Furthermore, Yamamoto teaches that remnants of the sponge were found in osseous or fibrous tissue (page 19, column 2, paragraph 7-page 24, column 2, paragraph 2 and Figures 1-5).
As Yamamoto does not irradiate the bone before implantation, regions of the ulna outside of the defect will still comprise bone marrow and blood vessels. Therefore, Yamamoto teaches an ulna (a bone product) that contains gelatin, compact bone, trabecular bone, blood vessels, and bone marrow upon implantation of the gelatin sponge loaded with BMP-2 and inoculated with bone marrow. Furthermore, upon isolation of the radius-ulna complex comprising the defect, the bone regeneration comprised trabecular bone, cortical bone, and gelatin sponge remnants. Although Yamamoto does not specifically identify that their isolated bone complex contained bone marrow and blood vessels, they identify that these components are essential for bone regeneration as their loss impaired bone regeneration. Therefore, the high levels of bone regeneration in the BMP-BM group positively identify bone marrow and blood vessels were present in the tissue to effectuate bone regeneration.
Regarding claims 3-4, Yamamoto teaches that bone marrow contains MSCs
and hematopoietic stem cells (page 24, column 1, paragraph 2).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Kusumoto et al. (British Journal of Plastic Surgery 51: 275-280. 1998; previous art of record) and further in view of Takahasi et al. (Biomaterials 26: 4856–4865. 2005). This is a new rejection made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Kusumoto teaches that they implanted a BMP-2 and collagen disk into a muscle pocket of the latissimus dorsi muscle flap. After three weeks, there was ectopic osteoinduction at the site of implantation and the tissue was removed for radiographical and histological examination (abstract and page 275, column 2, paragraph 2-page 276, column 2, paragraph 3). Kusumoto teaches that 3 weeks post-implantation, new bone tissue formed at the site of implantation. A mass of implanted collagen fibers was observed at the center of the lump. Osteoblasts lined the central side of trabeculae in a single line. A few osteoclasts directly contacted the trabecular bone. At the central side of the trabeculae, bone marrow partially containing angioid tissue was observed in some places. Angioid structures containing a circle of intimal cells and pooled red cells, were scattered throughout the mass (i.e. the lump consisted of trabeculum, bone marrow and remnants of collagen fibers) (page 276, column 2, paragraph 7 and Figure 4). Kusumoto teaches that after isolating the ectopic tissue, they resected the latissimus dorsi muscle flap comprising the ectopic bone tissue (page 276, column 1, paragraphs 2-4).
Kusumoto does not teach wherein they implant a gelatin sponge.
However, Takahashi teaches that they developed a gelatin sponge and incorporated BMP-2 into the sponge before implanting the sponge in the back subcutis of rats for ectopic bone induction (Abstract and Figures 3-4). Takahashi teaches that gelatin is a denatured collagen and commercially available as a biodegradable polymer. It has been extensively utilized for pharmaceutical and medical purposes, and its biosafety has been proven through the long clinical applications. Other advantages of gelatin are the easiness of chemical modification and the commercial availability of samples with different physicochemical properties. Additionally, it has been experimentally demonstrated that the attachment and proliferation of cells on substrates are promoted by the surface coating of gelatin. These findings suggest that gelatin is one of the materials compatible to cells (page 4857, column 1, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the collagen scaffold of Kusumoto with the gelatin sponge of Takahashi to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Takahashi successfully reduces to practice that collagen sponges incorporating BMP-2 also generate ectopic bone formation. Furthermore, Takahashi teaches that gelatin is a denatured collagen that has been extensively utilized for pharmaceutical and medical purposes, and its biosafety has been proven through the long clinical applications. Other advantages of gelatin are the easiness of chemical modification and the commercial availability of samples with different physicochemical properties. Additionally, it has been experimentally demonstrated that the attachment and proliferation of cells on substrates are promoted by the surface coating of gelatin. As such, gelatin, a derivative of collagen, would have been an obvious substitute for the biomaterial loaded with BMP-2 as it was known to also be osteoinductive for ectopic bone induction and safe. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Yamamoto et al. (Biomaterials 56: 18-25. 2015) and further in view of Heest et al. (Surgery 353: SI28-SI29. 1999). This is a new rejection made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
The teachings of Yamamoto are as discussed above.
Yamamoto does not teach administering the bone implant to a subject in need thereof.
However, Heest teaches that bone allografts have been used since 1881 when a tibial allograft was used successfully to treat a humeral defect. Allografts are now a source of bone for cortical, cancellous, or massive (entire bone or joint segments) grafts. An analysis of over 500 massive bone allografts used for the reconstruction of bone damage by tumour showed 75-80% success rate, based on patients being able to return to work and household activities with no infection, fracture or recurrence, these being the main complications of the procedure. The prophylactic measures adopted at large bone banks are sterilisation and regulations on donor suitability and are necessary for the prevention of the other disadvantage of allografts, disease transmission. The main advantage of allografts is their osteoconductive property. Their incorporation into the patient's skeletal structure enables the bone to respond to normal physiological stresses (page SI 28, column 1, paragraph 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the induced bone implant of Yamamoto with the allograft bone transplantation of Heest to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Yamamoto teaches that their bone implant is able to grow and regenerate in a bone defect already and Heest teaches that bone allografts have been extensively used to reconstruct bone damage. Therefore, it would have been obvious that the bone implant of Yamamoto could be used as a bone allograft to repair bone damage as it has already been shown to successfully repair bone damage and would have the appropriate factors for osteoinduction at the graft site. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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