DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
Acknowledgement is made of Applicants’ claim for benefit as a continuation of prior-filed US Application No. 16/520020 (filed 7/23/2019, now USP 11345889), which is a continuation of prior-filed US Application 14/651346 (now USP 10407664), which is a national stage entry of PCT/EP2013/076552 (filed 12/13/2013), which claims priority to foreign application EP 12196954.7 (filed 12/13/2012).
Election/Restrictions
Applicant's election with traverse of Group I, an artificial three-dimensional neural tissue culture, in the reply filed on 12/3/2025 is acknowledged. The traversal is on the ground(s) that Groups III and IV are not patentably distinct from Group I because they each require the product of Group I, and cannot individually be practiced with the product of Group I. This is not found persuasive because the product of Group I can be used in materially distinct processes (See Restriction Requirement of 9/4/2025 at Pg 3). Applicant’s arguments regarding Groups III and IV being “use-processes” is not understood, and does not find basis in the MPEP. The restriction between Groups III and IV is proper for the reasons set forth in the Restriction Requirement of 9/4/2025 Pgs 2-3. Reasons for holding search and/or examination burden were set forth in the Restriction Requirement of 9/4/2025 at Pg 3. The requirement is still deemed proper and is therefore made FINAL.
Claims 16-24 read on the elected invention. Claims 25-35 are withdrawn as being directed to non-elected inventions.
Claim Objections
Claim 17 is objected to for a minor informality: the word “form” is misspelled.
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 16-24 are 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 pre-AIA the applicant regards as the invention.
Regarding claims 16 and 24: the phrase “…a heterogeneous population of cells of at least two different progenitor and neuronal differentiation layers…” (lines 2-3 of claim 16, line 1-2 of claim 24) renders the claims indefinite because ‘progenitor and neuronal differentiation layers’ are not terms of the art, and are not defined in the specification, thus it is unclear what types of cells would be present in/derived from these layers. Because the limitation attempts to limit the cell types contained within the tissue, not being able to determine what cells types are present means the meets and bounds of the claim cannot be determined. For purposes of compact prosecution, the phrase will be interpreted as meaning at least two different cell types must be present.
Claims 17-24 depend directly or indirectly from claim 16, inherit the deficiencies, and are rejected on the same basis.
Regarding claim 17: there is insufficient antecedent basis for the limitation "said tissue sections” in line 1 of the claim.
Regarding claim 22: the claim is indefinite because it is unclear what is being defined/further limited. The claim fails to correlate the expression of forebrain markers/hindbrain markers to the tissue of parent claim 16 (or 21).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 16-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
In accordance with the Guidance for the December 16, 2014 update to the 2014 Interim guidance on Patent Subject Matter Eligibility (79 FR 74618), which can be found at http://www.uspto.gov/patent/laws-and-regulations/examination-policy/2014-interim-guidance-subject-matter-eligibility-0, the following analysis of the claims is made:
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation.
Regarding claims 16-24: The claims are directed to neural tissue cultures comprising at least two cell types, and at least one cell containing some genetic expression marker of a human brain.
The tissue cultures are compositions, which is a statutory category of invention (Step 1: YES).
The broadest reasonable interpretation of the claims covers developing human cortical cortex. Developing human cortical cortex comprises, in the following order (pial-to-apical surfaces): marginal zone, cortical plate, intermediate zone, outer subventricular zone, inner fiber layer, inner subventricular zone, ventricular zone. Outer radial glia cells are present in the outer subventricular zone (See Molnar et al, Nature Neuroscience, 2011, Fig. 1, Pg 539). Cells of the inner fiber layer are necessarily present in the inner fiber layer. Developing human cortical cortex meets the limitations of the instant claims as follows:
At least outer radial glial cells and inner fiber layer cells are present, thereby satisfying the limitation comprises at least two cell types.
The tissue contains seven layers, thereby satisfying the limitation of claim 17 wherein said tissue [sections] form at least two layers.
The outer radial glia cells are considered, in and of themselves, a ‘globular tissue body’, they are present within the outer subventricular zone, thus the outer subventricular zone is considered to read on a layer which is shaped around a globular tissue body, thereby satisfying the limitation of claim 18.
The developing human cortical cortex has a pial (i.e. dorsal) face and an apical face, thereby satisfying the limitation of claim 19 wherein said tissue develops apical and dorsal tissue sections.
The human cortical cortex is brain tissue, which is considered to read on cerebral tissue as required by claim 20.
With regard to expression of the markers (and expression levels) recited in claims 21-23: it is submitted that cells found naturally in the human developing brain at some point during development, express the markers, at the levels currently recited. This assertion is based on Applicants' own disclosure at page 10-11, where they describe naturally occurring brain cells as expressing each of the recited markers. Therefore, developing brain will inherently express each of the gene markers of claims 21-23. These genetic markers also satisfy the limitation of claim 15 that the tissue comprises a genetic expression of a marker of a human brain.
The individual cells of the radial glial cells and inner fiber cells do not contain blood vessels or a circulatory system, thereby satisfying the limitation of claim 24.
Thus, claims 16-24 read on developing human brain, which is a product of nature (judicial expectation). Therefore claims 16-24 are directed to a product of nature judicial exception (Step 2A: YES).
There are no additional elements recited in the claims that would amount to significantly more than the judicial exception (Step 2B: NO). Therefore claims 16-24 are patent ineligible as being directed to a judicial exception without significantly more.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(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.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claims 16-24 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by natural developing brain tissue, such as described by Molnar (Nature Neuroscience, 2011; on IDS).
Developing human cortical cortex comprises, in the following order (pial-to-apical surfaces): marginal zone, cortical plate, intermediate zone, outer subventricular zone, inner fiber layer, inner subventricular zone, ventricular zone. Outer radial glial cells are present in the outer subventricular zone (See Molnar et al, Nature Neuroscience, 2011, Fig. 1, Pg 539). Cells of the inner fiber layer are necessarily present in the inner fiber layer. Developing human cortical cortex meets the limitations of the instant claims as follows:
At least outer radial glia cells and inner fiber layer cells are present, thereby satisfying the limitation comprises at least two cell types.
The tissue contains seven layers, thereby satisfying the limitation of claim 17 wherein said tissue [sections] form at least two layers.
The outer radial glia cells are considered, in and of themselves, a ‘globular tissue body’, they are present within the outer subventricular zone, thus the outer subventricular zone is considered to read on a layer which is shaped around a globular tissue body, thereby satisfying the limitation of claim 18.
The developing human cortical cortex has a pial (i.e. dorsal) face and an apical face, thereby satisfying the limitation of claim 19 wherein said tissue develops apical and dorsal tissue sections.
The human cortical cortex is brain tissue, which is considered to read on cerebral tissue as required by claim 20.
With regard to expression of the markers (and expression levels) recited in claims 21-23: it is submitted that cells found naturally in the human developing brain at some point during development, express the markers, at the levels currently recited. This assertion is based on Applicants' own disclosure at page 10-11, where they describe naturally occurring brain cells as expressing each of the recited markers. Therefore, developing brain will inherently express each of the gene markers of claims 21-23. These genetic markers also satisfy the limitation of claim 15 that the tissue comprises a genetic expression of a marker of a human brain.
The individual cells of the radial glial cells and inner fiber cells do not contain blood vessels or a circulatory system, thereby satisfying the limitation of claim 24.
Claims 16-20 and 24 are rejected under pre-AIA 35 U.S.C. 102(a) and 102(e) as being anticipated by Livesey et al (WO 12/013936; on IDS).
Livesey et al describe polarized neuroepithelial rosettes that contain three cell populations:
a first cell population being Pax6+/Otx+/Ki67+, apico-basally polarized cells with radial processes, and which undergo IKNM and apical mitosis;
a second cell population that undergoes abventricular or basal mitoses; and
a third Tbr2+/Ki67+ population (See paragraph spanning pages 43-44).
Regarding claim 16: The rosettes of Livesey et al anticipate the in vitro grown artificial three-dimensional neural tissue culture of the instant claims. Specifically, they contain three cell types, making it a heterogeneous population of cells. The three different cell types are considered to satisfy the limitation cells of at least two different progenitor and neuronal differentiation layers (in giving the term its broadest reasonable interpretation, which would be different cell types). The various cells express Pax6, Otx, Tbr2 and Ki67, which are all markers found in cells of the human brain.
Regarding claims 17-19: The paragraph describing the cell types references Fig. 8. Fig. 8 is further described at Pg 32, ln 14-20, where Livesey reports the rosettes as polarized, having apical and dorsal tissue sections. The different cellular locations are considered at least two different layers, in concentric formation, which means at least one layer is shaped around a globular tissue body. The tissue has apical and dorsal tissue sections.
Regarding claim 20: The rosettes are cerebral tissue.
Regarding claim 24: There are no blood vessels or circulatory systems within the rosettes.
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 16-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10407664. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Regarding claims 16, 17, and 20: Patented claim 9 recites a three dimensional neural tissue culture that contains at least two types of cells, present in two layers. The types of cells present (outer radial glial cells and cortical inner fiber cells) necessarily express markers of the human brain. As the tissue contains cerebral cells, it can be considered cerebral tissue.
Regarding claims 18, 19, 21-23: Following the discussion of claim 16 above, patented claims 3 and 5-7 further teaching the limitations of claims 18, 19, and 21-23.
Regarding claim 24: The patented claims do not describe any blood vessel or circulatory system present.
Furthermore, it is noted that the method of patented claim 12 will inherently produce a tissue culture that anticipates all of claims 16-24. This is based on the disclosure of Example 1 within the patent.
Claims 16, 17, 20 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-12 of U.S. Patent No. 11884933. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Regarding claim 16: Patented claim 9 recites a three-dimensional artificial neuronal tissue culture that contains a multicellular aggregate containing neuronal differentiated cells. Patented claim 11 state the tissue culture further contains Map2 or radial glia cells. Patented claim 12 states the tissue culture further comprises radial glia and neurons. Thus the tissue culture of patented claims 11 and 12 comprise a heterogeneous population of cells. At least radial glia cells are found in the human brain, and thus express markers of a human brain.
Regarding claim 17: Patented claim 10 describes the tissue as having multiple layers.
Regarding claim 20: The patented tissue culture contains cells found in the brain, and thus can be considered cerebral tissue.
Regarding claim 24: The patented tissue culture does not recite presence of any blood vessels or circulatory system.
Claims 16 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-27 of copending Application No. 16/608719 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims.
Regarding claim 16: Copending claim 25 recites a bi- or multi-differentiated neuronal tissue with at least two neuronal tissue types of different stages of differentiation, wherein at least one of the tissue types is ventral neuronal tissue. This reads on a three-dimensional neural tissue culture comprising at least two different cell types. Given that one cell type is ventral neuronal tissue, the cell will necessarily have at least one marker found in human brain.
Regarding claim 20: Given that ventral neuronal tissue is a cerebral cell type, the tissue can be considered a cerebral tissue.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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