DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19 have been presented for examination on the merits.
Claim Objections
Claims 9-10 are objected to because of the following informalities: claims 9-10 include the percentage sign as ‰ (Should be %). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 9-10 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.
Claims 9-10 are indefinite for reciting that “wherein the one or more magnetic particles have an average coating concentration on the plurality of decellularized extracellular cartilage particles of 2-20% (or about 10 % in claim 10) wt/wt based on the weight of the one or more magnetic particles and a wet weight of the decellularized extracellular cartilage particles” in the implant of claim 1. This is indefinite because claim 1 is directed to a plurality of decellularized extracellular cartilage particles comprising one or more magnetic particles and MSCs. Thus, it is not clear what the basis for the claimed percentage is.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected 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. Claim 5 is dependent on claim 1 and only discloses the process of preparing the claimed plurality of decellularized extracellular cartilage particles. However, this is a product-by-process claim and the process is not given patentable weight. Thus, claim 5 fails to further limit the scope of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Applicant’s claims
Claim 1 is directed to a tissue-derived implant comprising: a plurality of decellularized extracellular cartilage particles, wherein each of the plurality of cartilage extracellular particles comprise one or more magnetic particles and mesenchymal stem cells (MSCs).
Claim 16 is directed to a method of treating a cartilage defect in a subject in need thereof, the method comprising: administering a therapeutically effective amount of the tissue-derived implant of claim 1 to the subject.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 5 is a product-by-process claim. According to MPEP § 2113 [R-1], product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
Claim Rejections - 35 USC § 103
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.
Claims 1-6, 9-10, 13-14, 16-17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Wei et al (Development of Magnet-Driven and Image-Guided Degradable Microrobots for the Precise Delivery of Engineered Stem Cells for Cancer Therapy) in combination with Nasert et al (US 20170049930).
Wei et al teach development of a magnet-driven and image-guided degradable microrobot that can precisely deliver engineered stem cells for orthotopic liver tumor treatment. The microrobot is actuated by a gradient magnetic field and guided by a unique photoacoustic imaging technology (See abstract).
Regarding claim 1, in part, Wei et al teach that biological modification of microrobot with extracellular matrix can further reduce stem cell differentiation and that they build stem cell niche with extracellular matrix to control stem cell differentiation (See Page 9, Discussion, 2nd Col.). It is disclosed that Fig. 1B shows a microrobot loaded with mesenchymal stem cells (MSCs) (middle) and confocal scan of visible GFP-labeled MSCs cultured on a microrobot (right). The cells carried are human-induced pluripotent stem cell-derived MSCs that can deliver glutathione peroxidase 3 (hiPSC-MSC-GPx3). It is also disclosed that Fe3O4 nanoparticles in 100 nm size were also added to polymer to achieve magnetic actuation (See Page 2, 1st Col.).
Regarding claims 9-10, in part, Wei et al teach magnetite nanoparticle solution (100 nm size, 260 mg mL-1 suspended in gamma-butyrolactone, and that the powder was added to the nanoparticle solution at the originally designed concentration (2 vol% Fe3O4 nanoparticle solution) (See page 11, both Cols.).
Regarding claim 16-17 and 19, in part, Wei et al teach developing degradable and image-guided microrobots to achieve automated navigation in vascular tissues for cell delivery, driven by an external gradient magnetic field actuation system. Ultrasound (US) imaging suffers from strong interference signal from backgrounds. Photoacoustic (PA) imaging detects optical absorption contrasts with high resolution and was recently used to detect the microrobots movement in mouse intestines (See abstract and Page 1). The said loaded microrobots are administered to a subject via transvascular treatment (See Page 12. 1st Col.).
Nasert et al teach cartilage fibers and implants made therefrom with cartilage particles, methods for making and administering them to treat a cartilage defect (See abstract).
Regarding claims 1 and 16-17, in part, Nasert et al teach decellularized extracellular matrix (ECM) providing support and anchorage for cells, segregating one tissue from another tissue, and regulating intracellular communication (See [0185] and [0189]). Disclosed cartilage-derived implant includes cartilage fibers, wherein the implant is used for treating cartilage defect (See [0011] and claim 21).
It is disclosed that the chondrocytes, cells found in cartilage that produce and maintain the cartilaginous matrix for, for example, joints, ear canals, trachea, epiglottis, larynx, wherein the chondrocytic lineage may be mesenchymal stem cell/marrow stromal cell (MSC) (See [0100], [0177]).
Regarding claim 4, Nasert et al teach that the cartilage is recovered from deceased human donors (See [0035]).
Regarding claims 2-3 and 13-14, in part, Nasert et al teach the cartilage particles have sizes in the range of 212 μm and less, or in the range of 500 μm and less (See [0085]).
Naser et al disclose mixtures that included less than about 35% by weight of the cartilage particles (See [0139]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Nasert et al with that of Wei et al to arrive at the instant invention. It would have been obvious to do so because both references teach making and administering a formulation comprising extracellular cells, a mesenchymal cell and magnetic particles. While Wei et al does not expressly disclose that the said extracellular matrix comprises decellularized extracellular cartilage cells (particles), Nasert et al teach that the use of decellularized extracellular cartilage cells in combination with mesenchymal cells for treating cartilage defects. Thus, it would have been obvious to one of ordinary skill in the art to have combined the teachings of Nasert et al into the combination of Wei et al and have selected decellularized extracellular cartilage cells as they are disclosed as beneficial in the said treatment.
One of ordinary skill in the art would also have been motivated to have taken guidance from Nasert et al on the particle sizes of extracellular particles with a reasonable expectation of success.
Regarding the concentration in claim 9-10, it is noted that these claims are rejected under 112(b) as being indefinite as it is not clear what the said percentages are based on. Additionally, based on the disclosures in Wei et al and Nasert et al, one of ordinary skill in the art would have been able to determine the suitable and desirable concentrations of each component. It is also noted that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955).
Thus, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Nasert et al (US 20170049930) in combination with Wei et al (Development of Magnet-Driven and Image-Guided Degradable Microrobots for the Precise Delivery of Engineered Stem Cells for Cancer Therapy) and Lopez Lopez et al (US 20180028661).
Teachings of Nasert et al and Wei et al are delineated above and incorporated herein.
The combined references lack an express disclosure on some particle sizes, concentration ranges and rotating magnetic field. These are known in the art as taught by Lopez Lopez et al.
Lopez Lopez et al’s teachings are on the field of tissue engineering. Specifically, the use of multiple magnetic domain particles that have a mean diameter greater than 25 nm, compositions and biomaterials comprising same, an in vitro method for producing an artificial tissue with the magnetic particles, the artificial tissue that can be produced by said method, and the use of said artificial tissue for partially or completely increasing, restoring or replacing the functional activity of a damaged organ or tissue are disclosed (See abstract).
Regarding claims 1, 5-8, 13-14, in part, Lopez Lopez et al teach a multiple magnetic domain particle that has a mean diameter greater than 25 nm, preferably, the mean diameter of the particles is between 50 and 1000 nm, even much more preferably between 75 and 200 nm. The said magnetic particles are of a ferro- or ferrimagnetic material, preferably iron or alloys thereof with other metals, and even more preferably iron oxides (See [0049]-[0050]).
Regarding claims 11 and 13-14, in part, Lopez Lopez et al teach that stem cells have been divided into: (a) embryonic stem cells: and (b) adult stem cells. Mesenchymal stem cells which are distributed in the connective tissue of different organs, such as, bone marrow, or umbilical cord, are included among adult stem cells. In a preferred embodiment, the adult stem cells are adult stem cells from the bone marrow. The cells from umbilical cord express different mesenchymal cell characteristic markers on their surface (See [0135]-[0137]).
Regarding claims 16-17, Lopez Lopez et al teach a device that comprises a) the multiple magnetic domain particles, the composition, the biomaterial or the artificial tissue, and b) an element capable of generating a magnetic field. The magnetic particles that are added in step (c), in the presence of the magnetic field. A magnetic field can be applied after step (e) to form the structures and additionally reinforce tissue elasticity (See [0033], [0075]-[0077]).
Regarding claim 18, it is disclosed that for the magnetic field, the axis is that of rotation of the rotating upper plate of the rheometer (See [0252]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Wei et al and Lopez Lopez et al with that of Nasert et al to arrive at the instant invention. It would have been obvious to do so because all references teach making and administering a formulation comprising extracellular cells, a mesenchymal cell and magnetic particles. Nasert et al teach that the use of decellularized extracellular cartilage cells in combination with mesenchymal cells for treating cartilage defects. Nasert et al does not teach the incorporation of iron oxides in the formulations. However, Wei et al and Lopez et al teach the benefit of incorporating magnetic particles including iron oxides and preferably Fe3O4 which creates a magnetic field and improves the treatment. Thus, it would have been obvious to one of ordinary skill in the art to have combined the teachings of Wei et al and Lopez Lopez et al into the formulations and methods of treatment of Nasert et al to achieve an effective treatment.
Additionally, one of ordinary skill in the art would also have been motivated to have taken guidance from Lopez Lopez et al on the particle sizes of extracellular particles and magnetic particles with a reasonable expectation of success.
Regarding the concentration in claim 9-10, it is noted that these claims are rejected under 112(b) as being indefinite as it is not clear what the said percentages are based on. Additionally, based on the disclosures in Wei et al and Nasert et al, one of ordinary skill in the art would have been able to determine the suitable and desirable concentrations of each component. It is also noted that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955).
Thus, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. CN 115252902.
CN 115252902 teach preparation of cartilage extracellular matrix and compositions comprising them. It is disclosed that the said cartilage extracellular matrix is prepared by by contacting the said particles with sodium dodecyl sulfate (See claim 1).
Claims 1-19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X. Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
Prosecution Insights