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 .
Priority
Acknowledgement is made of Applicant’s claim for benefit under 35 USC 121 as a divisional of prior-filed application 16/347939 (now USP 11458225), which is a national stage entry under 35 USC 371 of PCT/US2017/060666 (filed 11/08/2017), which claims benefit to US Provisional application 62/419835 (filed 11/9/2016).
It is set forth that the prohibition against nonstatutory double patenting rejections under 35 USC 121 [over parent patent 11458225] does not apply in the instant case because:
The claims of the application under examination and claims of the other application/patent (application resulting in US Patent 11458225) are not consonant with the restriction requirement made by the examiner in the parent patent application. The claims presented for examination in the instant case have been changed in material respects from the claims that were considered for restriction in the parent patent application at the time the requirement was made. See MPEP 804.01. Specifically, product claims 1-24, currently presented for examination, are narrower than product claim 31 which was considered for restriction in the parent patent application.
Claim Interpretation
Claim 1 is drawn to a three-dimensional, engineered ocular tissue model. The model comprises: a three-dimensional, engineered outer blood retinal barrier (oBRB), comprising:
a first layer comprising a choroid, the choroid comprising a first bio-ink comprising a plurality of endothelial cells;
a second layer comprising a plurality of retinal pigment epithelial cells,
and
(iii) a biocompatible scaffold present between the (i) first layer and (ii) second layer. (letterettes added by Examiner).
Though the claim states the (i) first and (ii) second layer form the three-dimensional engineered oBRB (see lines 6-7), given that the (iii) biocompatible scaffold is present between the (i) first and (ii) second layers, it is understood that the combination of the (i) first layer, (ii) second layer, and (iii) biocompatible scaffold form the three-dimensional oBRB.
The instant application defines “bio-ink” as a liquid, semi-solid, or solid composition for use in bioprinting (See page 9 of as-filed specification). Any material that can be used in bio-printing will satisfy the definition of ‘bio-ink’. As the claims are to the final product (model), not to the method of production, it is not necessary that the choroid have been bio-printing, but rather only that the choroid comprises a material which satisfies the definition of ‘bio-ink’ as well as a plurality of endothelial cells.
Claim Objection
Claims 2 and 17 are objected to for minor informalities:
In claim 2, the word “wherein” should follow the first comma.
In claim 17, line 3, “avitronectin” should be corrected to “a vitronectin”.
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.
Claim 2 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.
In claim 2, the species “collagen (vitrified or recombinant)” renders the claim indefinite. Specifically the portion in parenthesis renders the claim indefinite because it is not clear if the claim is limited to vitrified or recombinant collagen, or if these are merely examples of possible version of collagen. The metes and bounds of the claim are not clearly defined. See MPEP 2173.05(d).
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, 13-18 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tao et al (US 2011/0004304).
Tao et al disclose a bioreactor for culturing retinal tissue. The bioreactor includes (i) a first polymer layer defining a network of microchannels (also referred to as “plexus” or “microchannel layer”) that mimics the choriocapillaris, (ii) a second polymer layer forming a scaffold (also referred to as “microstructure scaffold”), and (iii) a porous thin film membrane separating the first polymer layer from the second polymer layer that mimics the Bruch’s membrane. The membrane is coated with retinal pigment epithelial (RPE) cells facing the second polymer layer (See ¶0015 & 0034). An illustration of the bioreactor structure relied upon is shown in Fig. 2B.
The (i) first polymer layer defining the network of microchannels (plexus/microchannel layer) is depicted as 252 of Fig. 2B (See ¶0038). It is described as a lattice-like network of microchannels formed from an artificial polymer (See ¶0040). The artificial polymer can be, inter alia, a non-degradable or degradable polymer material. “Harder” polymers can form the backbone of the scaffold, and ‘soft polymers’, such as hyaluronic acid, collagen, Matrigel or other gels can fill the openings (See ¶0018, 0035). Choroidal endothelial cells can be present in the microchannels (See ¶0036).
The (ii) second polymer layer forming a scaffold (microstructure scaffold) is depicted as 258 of Fig. 2B (See ¶0038).
The (iii) thin-film membrane is depicted as 256 in Fig. 2B (See ¶0038). A monolayer of RPEs (262 of Fig. 2B) is present on the side of the membrane facing the (ii) microstructure scaffold. The thin-film membrane can be formed from a polymer material, or from non-polymeric material, such as aluminum oxide or silicon oxide (See ¶0035). The thin-film membrane may be oxygen-plasma-treated or chemically functionalized with laminin, fibronectin, vitronectin, RGD or other protein sequences (See ¶0045). The membrane may be a polymer material having a Young’s modulus of at least 0.1 MPa to about 500 MPa (See ¶0043).
The embodiment of the bioreactor of Tao et al depicted in Fig. 2B, and containing choroidal endothelial cells within the (i) microchannel layer reads on the instant claims as follows:
Regarding claim 1: The cell-containing structure reads on a three-dimensional, engineered ocular tissue model.
The (i) microchannel layer formed of a lattice-like network of polymeric materials (e.g. 252 of Fig. 2B) and comprising choroidal endothelial cells reads on a first layer comprising a choroid. The polymeric material of the microchannel layer satisfies the limitation first bio-ink, as polymeric materials, particularly the “harder” polymers described in ¶0035, can be bio-printed. The choroidal endothelial cells read on a plurality of endothelial cells and can also be considered part of the first bio-ink.
The layer of RPE cells present on the (ii) thin film membrane (e.g. 262 of Fig. 2B) reads on a second layer comprising a plurality of retinal pigment epithelial cells.
The (iii) thin-film membrane (e.g. 256 of Fig. 2B) reads on a biocompatible scaffold, wherein the biocompatible scaffold is between the first layer and the second layer.
Regarding claims 13-15: Tao et al teaches the (i) microchannel layer can be filled with a gel material, including hyaluronic acid, collagen or Matrigel (which reads on a laminin hydrogel). As these hydrogels can be bio-printed, they will satisfy the limitation of bio-ink.
Regarding claims 16-17: Following the discussion of claim 1 above, Tao et al teach the membrane can be coated with extracellular matrix materials laminin or fibronectin. Thus the biocompatible scaffold further comprises an extracellular matrix that is coated on a surface of the biocompatible scaffold, including laminin or fibronectin.
Regarding claim 24: No nerve cells are disclosed within Tao et al, thus the structure is considered non-innervated.
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.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Tao et al (2011/0004304).
The teachings of Tao et al are set forth above.
Regarding claim 21: Tao et al differs from the instant claims in that they do not disclose the species of choroidal endothelial cells an RPE cells that can be used in their device.
However, it would have been prima facie obvious to have used any species of cells, including human cells in the method. Use of human cells, in particular, would create an allogenic (or autologous) graft that could be used in human medicine. There is implicit motivation to create materials that have therapeutic utility in human medicine. One would have had a reasonable expectation of success because human cells were readily available as of the effective filing date of the invention.
Claims 2-5 are rejected under 35 U.S.C. 103 as being unpatentable over Tao et al (2011/0004304), in view of Tao et al (WO 12/177968).
The teachings of Tao et al (‘304) are set forth above.
Regarding claim 2: Tao et al (‘304) describes the (ii) thin-film membrane as a polymeric material that is capable of supporting RPE cells. They teach that it can be oxygen-plasma-treated or chemically functionalized with laminin, fibronectin, vitronectin, RGD or other protein sequences (See Tao et al (‘304) ¶0045). However, Tao et al do not teach any specific polymeric material of the thin-film membrane.
Tao et al (‘968) is directed to culturing RPE cells on polymeric thin film membranes (See Tao et al (‘968) ¶0007). Tao et al (‘968) teach the polymeric membrane can be poly e-caprolactone (PCL) or a blend thereof. Tao et al (‘968) teach a variety of polymers, including those species recited in claim 2 (See Tao et al (‘968) ¶0009).
Because Tao et al (‘304) does not teach any particular species of polymers for the (ii) thin film membrane, it would have been obvious to one having ordinary skill in the art to look to related art to determine what specific polymers were appropriate for use as a thin film membrane for supporting culture of RPE cells. Tao et al (‘968) provides teaching that polymers such as PCL, PLGA, PGA, PLA, and collagen as well as co-polymers thereof were all suitable materials for such a polymeric membrane. Therefore it would have been prima facie obvious to have selected any of PCL, PLGA, PGA, PLA, collagen, or copolymers thereof, for use as the material for the thin film membrane in the bioreactor of Tao et al (‘304). This conclusion of obviousness is based on a teaching in the prior art. One would have had a reasonable expectation of successfully creating and using a thin film membrane made from PCL, PLGA, PGA, PLA, collagen, and/or copolymers thereof based on the disclosure of Tao et al (‘968).
Regarding claim 3: Following the discussion of claim 2 above, Tao et al (‘968) teach that PLGA is a suitable polymeric material. It is submitted that there are a finite number of variations of PGLA (combinations of the D and L isomers). Selection of PDGLA would have been at least obvious to try. It has been held that "a person with ordinary skill has good reason 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." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390. Given that Tao et al (‘968) teach that copolymers of PGLA are appropriate for use in the membrane, there is reasonable expectation that the various combinations of isomers would work substantially equivalently.
Regarding claim 4: Following the discussion of claim 3 above, neither Tao et al reference teach cross-linking the PDGLA. Official notice is taken that cross-linking affect the elasticity of a polymeric thin-film membrane. Tao et al (‘304) teaches that the polymeric material may be custom-tailored to have appropriate physical and chemical properties (See Tao et al (‘304) ¶0045). Cross-linking was standard as of the effective filing date. One having ordinary skill in the art would have found it prima facie obvious to have cross-linked the PDGLA membrane in order to achieve the desired elasticity and surface chemistry to optimize cell growth thereupon.
Regarding claim 5: Following the discussion of claim 3 above, Tao et al (‘304) teaches the membrane can be oxygen-plasma treated (See Tao et al (‘304) ¶0045).
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11458225.
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
Regarding claims 1, 13 and 24: Patented claim is directed to a method of fabricating a three-dimensional engineered BRB. The three-dimensional engineered BRB produced anticipates the instant claims. Specifically, the three-dimensional engineered BRB produced by the patented method will comprise:
A biocompatible scaffold having a first and second surface (reads on the biocompatible scaffold of the instant claims);
A hydrogel layer containing endothelial cells forming an artificial choroid on the first surface of the biocompatible scaffold (reads on the first layer comprising a choroid, the choroid comprising a first bio-ink, wherein the first bio-ink comprises a plurality of endothelial cells); and
RPE cells present on the second surface of the biocompatible scaffold (reads on a second layer comprising a plurality of RPE cells).
The combination of all the above layers reads on an outer blood retinal barrier. There are no nerve cells, so the model is not innervated.
Regarding claims 2-5: Patented claims 2-6 teach the chemical details of the biocompatible scaffold.
Regarding claims 6-12, 18 and 19: Patented claims 7-12 teach the presence of additional fibroblasts and pericytes and teach the ratios and amounts required by claims 6-12, 18 and 19.
Regarding claims 14-15: Patented claims 14-15 teach the hydrogel can be those species recited by instant claims 14-15.
Regarding claims 16-17: Patented claims 18-19 teach the biocompatible scaffold can be coated with ECM components.
Regarding claim 20: Patented claim 23 teaches the RPE cell detail of claim 20.
Regarding claims 21-23: Patented claims 12 and 26 teach the endothelial cells, RPE cells, fibroblasts and pericytes are human cells.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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