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 .
Claim Status
Claims 1-20 are pending.
Claims 12-20 are withdrawn.
Claims 1-11 are under examination.
Examiner’s Remark on Domestic Benefit
This Application is Continuation in-part of U.S. Application No. 18/735,858, filed 6th, June 2024.
U.S. Application No. 18/735,858 claims domestic benefit to U.S. Provisional Application No. 63/506,521 filed on 6th, June, 2023.
Instant claim 1, upon which all claims under examination depends, requires that the hSCO comprises immune cells. It is noted that there is no support for an hSCO comprising immune cells in U.S. Provisional Application No. 63/506,521 filed on 6th, June, 2023. In fact, U.S. Provisional Application No. 63/506,521 specifically discloses an hSCO that excludes immune cells (“the absence of
immune and endothelial cells” on pg. 5 and “no microglia” on pg. 5 and 12; Example 4).
It is noted that the originally filed disclosure of U.S. Application No. 18/735,858 provides no support for an hSCO comprising immune cells. In fact, U.S. Application No. 18/735,858 specifically discloses an hSCO that excludes immune cells (“The absence of immune and endothelial cells” pg. 6; “no microglia” pg. 6; “the hSCO does not comprise detectable microglia” pg. 7; see also pg. 9 and 14).
Therefore, because the required element of “immune cells” of instant claims is not supported by U.S. Provisional Application No. 63/506,521 or U.S. Application No. 18/735,858, the instant claims have been given the effective filing date of the instant Application, which is the 3rd of July, 2025.
Election/Restrictions
Applicant’s election of the following invention
Invention
Group I - Claims 1-11, drawn to a human spinal cord organoid in the reply filed on 8th, June, 2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Objections to Drawings
This Application contains color drawings. It is noted that Applicant has filed a petition filed under 37 CFR 1.84(a)(2) is granted. Since the petition has not yet been reviewed, the drawings are objected to.
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 the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, 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).
Objections to Drawings
The Drawings are objected to because they do not conform to sequence rules, requiring the use of “SEQ ID NO:” (37 CFR 1.821-1.825)(see also MPEP 2422.01).
Figures 9A-9B contain amino acid sequences that do not reference a corresponding sequence identifier.
Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. 37 CFR 1.821 (d).
The applicant is reminded that claims and specification must be amended in order to comply with regulations cited above. All references to sequences in claims and specification should be referred to as “SEQ ID NO:1”, for example. To avoid all doubts of the examiner and to ensure correct interpretation of the claims and specification, the identification of sequences with proper sequence identifiers is required.
Objections to Specification
The specification is objected to because it does not conform to sequence rules, requiring the use of “SEQ ID NO:” (37 CFR 1.821-1.825)(see also MPEP 2422.01).
The amino acid sequence “IKVAV” on pg. 5 lines 13 and 19; pg. 6 lines 27-28; pg. 31 line 30; pg. 33 line 26; pg. 34 lines 27 and 29; pg. 40 line 27; and pg. 41 lines 8 and 18 is not labeled with a corresponding sequence identifier.
Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. 37 CFR 1.821 (d).
The applicant is reminded that claims and specification must be amended in order to comply with regulations cited above. All references to sequences in claims and specification should be referred to as “SEQ ID NO:1”, for example. To avoid all doubts of the examiner and to ensure correct interpretation of the claims and specification, the identification of sequences with proper sequence identifiers is required.
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.
Claims 1-7 and 9-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
Step 1
In regard to step 1, the claims are directed to a human spinal cord organoid (hSCO), which is a product and is a statutory class of invention. Accordingly, the requirements of step 1 are met.
Step 2A Prong One
In regard to Step 2A prong one, as stated above, the claims are directed to a human spinal cord organoid, which is a nature-based product.
Since the claims are directed to a nature based-product, the nature based-product is reviewed to determine whether or not it possesses markedly different characteristics (see MPEP 2106.04(c) for The Markedly Different Characteristics Analysis).
Applicant is directed to the art of Valdes-Gorcia et al. (Acta Neurochir (Wien) . 1998;140(9):899-903.; henceforth “Valdes-Gorcia”). Valdes-Gorcia evidences biopsies of naturally occurring human brainstem and Posterior Fossa tissue lesions (Figures 1-3; pg. 900 “Patients and Methods”).
Applicant is additionally directed to the art of Serrano et al. (J Tissue Sci Eng
. 2021;12(4):242.. Epub 2021 Oct 13.; henceforth “Serrano”). Serrano evidences naturally occurring human brain (“Fresh brain samples” Materials and methods pg. 2-3).
The naturally occurring brain tissue evidenced above meets the structural requirements of instant claims for the following reasons.
Regarding claims 1-3, the naturally occurring lesion biopsies of Valdes-Gorcia and the naturally occurring brain of Serrano comprise neural cells, astroglial cells, and microglial cells which are immune cells.
Regarding claim 4, further to the discussion of claims 1-3 above, because TUJ-1 is a neuronal marker, IBA-1 microglia marker, and GFAP is an astrocyte marker, these would be expressed by the neural cells, astroglial cells, and microglial cells of the naturally occurring lesion biopsies of Valdes-Gorcia and the naturally occurring brain of Serrano.
Regarding claim 5, further to the discussion of claim 1 above, brain tissue and brainstem tissue includes oligodendrocytes which make up the myelin sheath and therefore the naturally occurring lesion biopsies of Valdes-Gorcia and the naturally occurring brain of Serrano would comprise these cells.
Regarding claim 6, naturally occurring human brains are substantially spherical in shape.
Regarding claims 6-7, the naturally occurring human brains evidenced by Serrano have an average diameter of greater than 2 mm or 2.5 mm.
Regarding claim 11, the naturally occurring brainstem tissue lesion biopsies of Valdes-Gorcia have received an injury (lesion). Applicant is directed to the art of Fitch et al. (Exp Neurol
. 2008 Feb;209(2):294-301. Epub 2007 May 31.; henceforth “Fitch”). Fitch evidences glial scar (see “glial scarring was demonstrated in an in vivo model of inflammation” pg. 296 col. 2) and chondroitin sulfate proteoglycans (see “Chondroitin sulfate proteoglycans are found in the brain after stab wound, in the spinal cord after injury to the dorsal root, and in the spinal cord following injury” pg. 296 col. 1) occur in response to neural tissue injury and therefore the naturally occurring brainstem tissue lesion biopsies of Valdes-Gorcia which have received an injury would naturally comprise these structures.
Therefore, because the structures required by the claims are met by naturally occurring brain tissue and biopsies for the reasons set forth above, the organoid as presently claimed does not possess markedly different characteristics.
Step 2A, Prong Two
Because the claims are directed to a nature-based product that does not possess markedly different characteristics, the additional elements recited in the claims are reviewed to determine whether the judicial exception is integrated into a practical application.
In regard to Step 2A prong two, the judicial exception is not integrated into a practical application.
Claim 1 recites the additional elements of:
“spinal cord” and “organoid” in the preamble
Because the structures of the body of the claim are met by the naturally occurring brain tissue and biopsies above, merely labeling with the intended use as “spinal cord” does not integrate the naturally occurring product into a practical application.
Labeling the tissue as an organoid in the preamble does not integrate into a practical application because, as stated above, the structural limitations of the body of the claim are met by the naturally occurring brain tissue and biopsies above. Merely labeled it as an “organoid” does not integrate the naturally occurring product into a practical application.
Claim 6 recites the additional elements that the organoid is “substantially spherical in shape” which does not integrate into a practice application because it merely includes the shape of the tissue and reads on dissected pieces of naturally occurring brain tissue that would be considered “substantially spherical in shape.” Furthermore, as stated above, (see Step 2A Prong One), this is met by the shape of a naturally occurring brain.
Claims 6-7 recites the additional elements that the organoid has an average diameter of at least 2 (instant claim 6) or 2.5 mm (instant claim 7) which does not integrate into a practice application because it merely includes the size of the tissue and reads on sizes of dissected pieces of naturally occurring brain tissue as well as different sizes of brain tissue biopsy punches. Applicant is additionally directed to the art of Sanai et al. (Neurosurgery. 2008 Sep;63(3):460-6; discussion 466-8.; henceforth “Sanai”) which evidences standard brain tissue biopsies are made with a 9 mm opening (“the standard 9-mm opening” pg. 461 col. 2) and would it would be routine and conventional for these biopsies to be greater than at least 2 (instant claim 6) or 2.5 mm (instant claim 7). Furthermore, as stated above, (see Step 2A Prong One), these sizes are also already met by ta naturally occurring brain.
Claims 9-10 each recite additional elements of culture times of “at least about 8 Weeks” (instant claim 9) and “about 8 weeks to about 28 weeks” (instant claim 10). These do not integrate into a practical application because they merely recite the amount of time the tissue has been in culture and do not on their own impart an additional structure because they are product-by process limitations and they do not on their own integrate into a practical application because they do not require any additional elements or steps.
Claim 11 recites the additional element that the organoid “has received an injury and comprises glial scar-like tissue and chondroitin sulfate proteoglycans (CSPGs) as a result of the injury. ” First, this is product-by process language and does not require additional steps, only the structure that is implied by the steps. As set forth above, injured brain tissue is naturally occurring (see Step 2A Prong One), and Fitch evidences the recited glial scar-like tissue and chondroitin sulfate proteoglycans (CSPGs) are expected structures that result from injury and therefore these additional elements recite expected structures and cannot integrate into a practical application.
Step 2B
Since the claims recite an organoid that is not markedly different from its naturally occurring counterpart, and does not integrate into a practical application, the claims are reviewed to determine if they recite elements that amount to sufficiently more than the judicial exception.
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim 1 recites the additional elements of:
“spinal cord” and “organoid” in the preamble
Because the structures of the body of the claim are met by the naturally occurring brain tissue and biopsies above, merely labeling with the intended use as “spinal cord” does not amount to significantly, more.
Labeling the tissue as an organoid in the preamble does not amount to significantly more because, as stated above, the structural limitations of the body of the claim are met by the naturally occurring brain tissue and biopsies above.
Claim 6 recites the additional elements that the organoid is “substantially spherical in shape” which does not amount to significantly more because it merely includes the shape of the tissue and reads on dissected pieces of naturally occurring brain tissue that would be considered “substantially spherical in shape.” Furthermore, as stated above, (see Step 2A Prong One), this is met by the shape of a naturally occurring brain.
Claims 6-7 recites the additional elements that the organoid has an average diameter of at least 2 (instant claim 6) or 2.5 mm (instant claim 7) which does not amount to significantly more because it merely includes the size of the tissue and reads on sizes of dissected pieces of naturally occurring brain tissue as well as different sizes of brain tissue biopsy punches. Applicant is additionally directed to the art of Sanai et al. (Neurosurgery. 2008 Sep;63(3):460-6; discussion 466-8.; henceforth “Sanai”) which evidences standard brain tissue biopsies are made with a 9 mm opening (“the standard 9-mm opening” pg. 461 col. 2) and would therefore be greater than at least 2 (instant claim 6) or 2.5 mm (instant claim 7) and it would be routine and convention to obtain biopsies of that size. Furthermore, as stated above, (see Step 2A Prong One), these sizes are also already met by ta naturally occurring brain.
Claims 9-10 each recite additional elements of culture times of “at least about 8 Weeks” (instant claim 9) and “about 8 weeks to about 28 weeks” (instant claim 10). These do not amount to significantly more because they merely recite the amount of time the tissue has been in culture and do not on their own impart an additional structure because they are product-by process limitations and they do not on their own amount to significantly more because they do not require any additional elements or steps.
Claim 11 recites the additional element that the organoid “has received an injury and comprises glial scar-like tissue and chondroitin sulfate proteoglycans (CSPGs) as a result of the injury. ” First, this is product-by process language and does not require additional steps, only the structure that is implied by the steps. As set forth above, injured brain tissue is naturally occurring (see Step 2A Prong One), and Fitch evidences the recited glial scar-like tissue and chondroitin sulfate proteoglycans (CSPGs) are expected structures that result from injury and therefore these additional elements recite expected structures and do not amount to significantly more.
Therefore, the claims are directed to a naturally occurring product (natural liver brain tissue) that is not integrated into a practical application, does not include elements that amount to significantly more than the judicial exception, and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
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 9 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.
Claim 9 recites the phrase “at least about” with no corresponding special definition of “at least about.” Thus, there is nothing in the specification, prosecution or prior art to provide any indication as to the claimed range, thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(b), III.A. Additionally, the phrase “at least” creates a hard lower cutoff for the value, but the term “about” indicates there is a range for the stated value. Including both “at least” and “about” makes it unclear whether or not the lower value is a hard cutoff for the range.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5 and 8-10 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”).
Regarding claims 1-3, Skibinski discloses a human neuroimmune organoid (“human-derived brain organoid” para. [0004] and “NICOs that have microglia integrated” para. [00021]), comprising
neural cells (MAP2 positive neurons para. [000180]; see also para. [00017-00018, 00023, 00026, 00031, 00033, 00035, 00039-00040, 00049, 00059-00060, 00063, 00065-00066, 00069, 00071, 00078, 00081, 00092-00094, 000111-000112, 000150-000151, 000183-000184, 000189, 000202, 000205, 000208, 000216, 000218, 000220-000222]; Examples 5, 13-15, 19, 21, 23, 25; claims 15, 54-558; Figures 3B-C, 20A)
astroglial cells (astrocytes; para. [00017, 00033, 00035, 00063, 00078, 000180, 000183, 000205, 000218, 000220-000221]; claim 15, 60, 71; Figure 20B; Examples 4, 20-21),
and immune cells that are microglia cells, which are a specialized type of macrophage (instant claims 2-3) (“microglia” para. [0004-0005, 0007, 00018-00037, 00039, 00041-00042, 00045-00047, 00049, 00051-00055, 00059, 00061, 00063, 00065, 00068-00073, 00075-00078, 000116-000123, 00172-000173, 000178, 000180, 000187-000188, 000190-000200, 000202-000204, 000206, 00208-000211, 000213-000226]; Examples 2, 7-8, 10-28; claims 1, 6-8, 10-11, 13-15, 18, 20-22, 31-32, 64, 67, 69-72, 75, 77; Figure 6B)see also Figures 4A-C, 5A-5D, 6A-6F; para. [00019-0022]; Example 4).
Regarding the preamble of “a human spinal cord organoid (hSCO)” of claim 1, Skibinski specifically discloses that the organoid may have spinal cord features (para. [00064]) and may express spinal cord markers (para. [00063-00066]). Skibinski specifically discloses the organoid may be “spinal-cord NICO” (para. [00066]), and may be a model of the spinal cord (para. [00085]). Therefore, the organoids of Skibinski are capable of meeting the intended use as a human spinal cord organoid recited in the preamble.
Furthermore, regarding the preamble of “a human spinal cord organoid (hSCO)” of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and therefore the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). The organoid disclosed by Skibinski comprises all the structural elements of the body of instant claims and therefore is capable of meeting the intended use as human spinal cord organoid (hSCO).
Regarding claim 5, further to the discussion of claim 1 above, Skibinski discloses the organoid further comprises oligodendrocytes (claim 61; para. [000184]; Figures 2A-2B).
Regarding claim 8, further to the discussion of claim 1 above, the astroglial cells (astrocytes) of the organoid of Skibinski are present on an outer surface of the organoid which is substantially smooth (Figures 5A-C).
Regarding claims 9-10, further to the discussion of claim 1 above, Skibinski discloses the organoid has been cultured for 100+ days (para. [00017, 000184]; Figures 2A-2B), which includes that the organoid has been cultured for at least 56 days (8 weeks) (instant claim 9), and has been cultured for 56 days to 196 days (8 to 12 weeks) (instant claim 10).
Accordingly, Skibinski anticipates instant claims.
Examiner’s Remark
The prior art of Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”) applied above is prior art under both 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2). WO 2023/220453 A2 is published internationally 16th, November, 2023 which pre-dates the effective filing date of the instant Application of 3rd of July, 2025 and it is therefore prior art under 35 U.S.C. 102(a)(1). WO 2023/220453 A2 is also a WIPO publication by another inventor that designates the United States and was effectively filed 13th, May, 2022 which is before the effective filing date of the claimed invention and it is therefore prior art under 35 U.S.C. 102(a)(2). To overcome this rejection, Applicant will need to overcome both the rejection 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Skibinski.
Claims 1-3 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schafer et al. (Cell. 2023 May 11;186(10):2111-2126.e20.; henceforth “Schafer”).
Regarding claims 1-3, Schafer discloses an immunocompetent human brain organoid (iHBO) (summary; pg. 2112 col. 1) comprising neural cells, astroglial cells, and microglia (instant claims 2-3) which are immune cells (see figure 3C “Heatmaps showing expression of neuronal marker genes SATB2 and TBR1 , astrocyte marker genes S 100B and EAAT1, and microglia-supporting factors IL34 and CSF1”) (see also Figures S1 and S3).
Regarding the preamble of “a human spinal cord organoid (hSCO)” of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). The organoid disclosed by Schafer comprises all the structural elements of the body of instant claims and therefore is capable of meeting the intended use as human spinal cord organoid (hSCO).
Regarding claims 6-7, further to the discussion of claim 1 above, the organoid disclosed by Schafer is substantially spherical in shape, and has an average diameter of more than 2 mm and more than 2.5 mm (diameter of greater than 5 lengths of the 500 µm scalebar in Figure S3B).
Accordingly, Schafer anticipates instant claims.
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 1-4 and 6-10 rejected under 35 U.S.C. 103 as being unpatentable over Ramirez et al. (Cells. 2021 Oct 7;10(10):2683.; henceforth “Ramirez”) in view of Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”).
Regarding claims 1-3, Ramirez discloses a human neural organoid (Human Cerebral Organoids; see pg. 3 2nd para. “2.2. Cerebral Organoid Generation”) comprising an inner layer comprising neural cells and outer layer comprising glial cells (“fully differentiated neurons and astrocytes was analyzed by immunostaining with MAP2 (E) and GFAP (F)” see Figure 2 and Figure S3).
However, regarding claims 1-3, Ramirez is silent to including microglia cells (instant claims 2-3), which are immune cells (instant claim 1), in the organoid. Ramirez teaches one of the main limitations of the neural organoids is that they lack glial cells, which led to an inability to model some of the crucial features of TBI, such as microglial activation, cerebral hemorrhages, and edema (pg. 15 3rd. para.).
Nevertheless, regarding claims 1-3, Skibinski teaches incorporating microglia, which are a specialized type of macrophages and are immune cells, into a human neural organoid (“integration of microglia (IBA-1) throughout the CO tissue” para. [00019] and Figure 4A; see also para. [0004-0005, 0007, 00018-00037, 00039, 00041-00042, 00045-00047, 00049, 00051-00055, 00059, 00061, 00063, 00065, 00068-00073, 00075-00078, 000116-000123, 00172-000173, 000178, 000180, 000187-000188, 000190-000200, 000202-000204, 000206, 00208-000211, 000213-000226]; Examples 2, 7-8, 10-28; claims 1, 6-8, 10-11, 13-15, 18, 20-22, 31-32, 64, 67, 69-72, 75, 77; Figure 6B)see also Figures 4A-C, 5A-5D, 6A-6F; para. [00019-0022]; Example 4). Skibinski teaches incorporation of microglia results in an organoid that has properties that approximate complex neurological systems and are useful in drug screening and neural disease modeling (para. [0003]). Skibinski teaches Microglia incorporated into the CO tissue show a decrease in oxidative stress response genes and an upregulation of phagocytosis genes, indicating that microglia are more physiologically relevant (para. [00023]). Skibinski teaches microglia incorporation into COs significantly increased dendritic (MAP2) and astrocytic (GFAP) density within the CO and there was also a trend towards an increase in synaptic density (PSD95) (para. [00025]).
Therefore, regarding claims 1-3, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the organoid of Ramirez, and combine the known prior art element of the incorporation of microglia of Skibinski to obtain the predictable result of a neuroimmune organoid. One of ordinary skill would have been motivated to do so as taught by Skibinski to obtain an organoid that has properties that approximate complex neurological systems and are useful in drug screening and neural disease modeling (para. [0003]), is more physiologically relevant (para. [00023]), and has increased dendritic, astrocytic and synaptic density (para. [00025]). Furthermore, one of ordinary skill would have been motivated to do so as taught by Ramirez to model some of the crucial features of TBI, such as microglial activation, cerebral hemorrhages, and edema (pg. 15 3rd. para.). Regarding the reasonable expectation of success, Skibinski evidences incorporation of microglia into a neural organoid comprising neural cells and astroglial cells (astrocytes) (Examples 3-4).
Regarding the preamble of “a human spinal cord organoid (hSCO)” of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). The organoid suggested by Ramirez in view of Skibinski comprises all the structural elements of the body of instant claims and therefore is capable of meeting the intended use as human spinal cord organoid (hSCO).
Regarding claim 4, further to the discussion of claims 1-3 above, Ramirez teaches the neural cells express class III beta-tubulin (TUJ-1) (“β tubulin (Tuj1) positive neurons” Figure 2) and the astroglial cells express GFAP (GFAP) (abstract; Table 2; pg.7 1st para.; pg. 8 1st para.; pg. 13 2nd para.; Figures 2-3 and Figure S3), and the microglia suggested by Skibinski express IBA-1 (Para. [00019, 00021, 00025, 00030, 00036, 00041-00042, 00065, 000173, 000191, 000194-000197, 000203-000206, 000215, 000221]; Figure 4A-C) and therefore it would be obvious that the organoid suggested by Ramirez in view Skibinski above, would include neural cells that express TUJ-1, astrocytes that express GFAP, and microglia that express IBA-1.
Regarding claims 6-7, Ramirez teaches the organoid is substantially spherical in shape (see Figures S3 and S5) (instant claim 6) and has an average diameter of at least 2 mm (instant claim 6) or greater than 2.5 mm (instant claim 7) (the CO in Figure S5 has a diameter of slightly more than 3 lengths of the 1 mm scalebar which is more than 3mm).
Regarding claim 8, further to the discussion of claim 1 above, Ramirez teaches the astroglial cells (GFAP positive astrocytes) are present on an outer surface of the organoid, wherein the outer surface is substantially smooth (see Figure 2 of Ramirez).
Regarding claim 9, further to the discussion of claim 1 above, Ramirez teaches culturing the organoid for 220 days in vitro (DIV) which is 31.4 weeks and is encompassed by the claimed “at least 8 weeks” (“the CCI procedure was done at 220 days in vitro (DIV)” pg. 3 2nd para.).
Regarding claim 10, further to the discussion of claims 1 and 9 above, as stated above, Ramirez teaches the organoid of Ramirez has been cultured for 220 days in vitro (DIV) which is 31.4 weeks prior to mechanical injury and is encompassed by the upper range of the claimed “about 28 weeks” and includes culturing for about 8 weeks to about 28 weeks.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Ramirez et al. (Cells. 2021 Oct 7;10(10):2683.; henceforth “Ramirez”) in view of Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”) as applied to claim 1 above, and in further view of Fitch et al. (Exp Neurol . 2008 Feb;209(2):294-301. Epub 2007 May 31.; henceforth “Fitch”).
The teachings of Ramirez and Fitch above are incorporated herein in their entirety.
Regarding claim 11, further to the discussion of claim 1 above, Ramirez teaches the organoid has been injured (the organoid of Ramirez has been exposed to the controlled cortical impact (CCI) model; abstract; Introduction; pg4-5 “2.7. Controlled Cortical Impact Procedure in Cos)) and contains glial scar-like tissue comprising reactive astrocytes (“CCI also induced a significant increase in GFAP immunoreactivity in COs” pg. 8 1st para.; “GFAP positive cells in CCI-impacted COs displayed hypertrophic process” and “significant increase in GFAP immunoreactivity” pg. 8 1st para).
However, regarding claim 11, Ramirez is silent to chondroitin sulfate proteoglycans (CSPGs) chondroitin sulfate proteoglycans (CSPGs).
Nevertheless, regarding claim 11, Fitch teaches that chondroitin sulfate proteoglycans are present as a response to injury and glial scar (see “Chondroitin sulfate proteoglycans are found in the brain after stab wound, in the spinal cord after injury to the dorsal root, and in the spinal cord following injury” pg. 296 col. 1). Fitch teaches reactive astrocytes within glial scar have been shown to upregulate chondroitin sulfate proteoglycans (pg. 295 col. 2).
Therefore, regarding claim 11, it would have been obvious to a person of ordinary skill in the art that the organoid suggested by Ramirez in view of Skibinski, which includes glial scar and reactive astrocytes and has undergone an injury, would comprise chondroitin sulfate proteoglycans because Fitch teaches this is an expected result of neural tissue undergoing an injury and having glial scar.
Hence, the claimed invention as a whole was prima facie obvious.
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.
Provisional Non-Statutory Double Patenting
U.S. Co-pending Application No. 18/735,858
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-8 of copending application No. 18/735,858 (claim set filed 5th, June, 2026) in view of Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the human spinal cord organoid anticipates or makes obvious the human spinal cord organoid of the instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claims 1-3, U.S. Co-pending App ‘858 claims a human spinal cord organoid (hSCO) comprising neural cells and astroglial cells (reactive astrocytes; claim 1) (claims 1-2 and 4-8).
However, regarding claims 1-3, U.S. Co-pending App ‘858 does not claim that the organoid includes microglia cells (instant claims 2-3), and are immune cells (instant claim 1), in the organoid.
Nevertheless, regarding claims 1-3, Skibinski teaches incorporating microglia, which are immune cells, into a human neural organoid (“integration of microglia (IBA-1) throughout the CO tissue” para. [00019] and Figure 4A; see also para. [0004-0005, 0007, 00018-00037, 00039, 00041-00042, 00045-00047, 00049, 00051-00055, 00059, 00061, 00063, 00065, 00068-00073, 00075-00078, 000116-000123, 00172-000173, 000178, 000180, 000187-000188, 000190-000200, 000202-000204, 000206, 00208-000211, 000213-000226]; Examples 2, 7-8, 10-28; claims 1, 6-8, 10-11, 13-15, 18, 20-22, 31-32, 64, 67, 69-72, 75, 77; Figure 6B)see also Figures 4A-C, 5A-5D, 6A-6F; para. [00019-0022]; Example 4). Skibinski teaches incorporation of microglia results in an organoid that has properties that approximate complex neurological systems and are useful in drug screening and neural disease modeling (para. [0003]). Skibinski teaches Microglia incorporated into the CO tissue, show a decrease in oxidative stress response genes and an upregulation of phagocytosis genes, indicating that microglia are more physiologically relevant (para. [00023]). Skibinski teaches microglia incorporation into COs significantly increased dendritic (MAP2) and astrocytic (GFAP) density within the CO and there was also a trend towards an increase in synaptic density (PSD95) (para. [00025]).
Therefore, regarding claims 1-3, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the organoid as claimed by U.S. Co-pending App ‘858 and combine the known prior art element of the incorporation of microglia of Skibinski to obtain the predictable result of a neuroimmune organoid. One of ordinary skill would have been motivated to do so as taught by Skibinski to obtain an organoid that has properties that approximate complex neurological systems and are useful in drug screening and neural disease modeling (para. [0003]), is more physiologically relevant (para. [00023]), and has increased dendritic, astrocytic and synaptic density (para. [00025]). Regarding the reasonable expectation of success, Skibinski evidences incorporation of microglia into a neural organoid comprising neural cells and astroglial cells (astrocytes) (Examples 3-4).
Regarding claim 4, further to the discussion of claims 1-3 above, U.S. Co-pending App ‘858 claims the neural cells express class III beta-tubulin (TUJ-1) and wherein the glial cells express glial fibrillary acidic protein (GFAP) (claim 2) and the microglia suggested by Skibinski express IBA-1 (Para. [00019, 00021, 00025, 00030, 00036, 00041-00042, 00065, 000173, 000191, 000194-000197, 000203-000206, 000215, 000221]; Figure 4A-C) and therefore it would be obvious that the organoid as claimed by U.S. Co-pending App ‘858 in view Skibinski above, would include neural cells that express TUJ-1, astrocytes that express GFAP, and microglia that express IBA-1.
Regarding claim 5, further to the discussion of claim 1 above, while U.S. Co-pending App ‘858 claims the organoid comprises glial cells, U.S. Co-pending App ‘858 does not claim the organoid comprises oligodendrocytes which are a type of glial cell.
Nevertheless, regarding claim 5, Skibinski teaches including oligodendrocytes in a neural organoid because the presence of oligodendrocyte precursors and astrocytes is critical for neuronal maturation and function (para. [00017]; see also para. [0049, 0060, 0063, 00078, 000154, 000184]; claim 61).
Therefore, regarding claim 5, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the organoid as claimed by U.S. Co-pending App ‘858, and combine the known prior art element of the oligodendrocytes of Skibinski to obtain the predictable result of a neural organoid. One of ordinary skill would have been motivated to do so as taught by Skibinski to promote the development of neuronal maturation and function (para. [00017]; see also para. [0049, 0060, 0063, 00078, 000154, 000184]; claim 61). Regarding the reasonable expectation of success, Skibinski evidences preparation of neural organoids comprising oligodendrocytes (para. [00017]; see also para. [0049, 0060, 0063, 00078, 000154, 000184]; claim 61).
Regarding claim 6, further to the discussion of claim 1 above, U.S. Co-pending App ‘858 claims the hSCO is substantially spherical in shape and has an average diameter of at least 2 mm (claim 1).
Regarding claim 7, further to the discussion of claim 1 above, U.S. Co-pending App ‘858 claims the hSCO has an average diameter of at least 2.5 mm (claim 4).
Regarding claim 8, further to the discussion of claim 1 above, U.S. Co-pending App ‘858 claims the astrocytes are present on an outer surface of the organoid (an outer layer containing glial cells which includes the astrocytes). Although U.S. Co-pending App ‘858 does not specifically claim the organoid is substantially smooth, this is an obvious feature of the outer surface of an organoid (see, for example, Figures 5A-C of Skibinski) and therefore would be obviously met by the suggested organoid.
Regarding claim 9, further to the discussion of claim 1 above, U.S. Co-pending App ‘858 claims the hSCO has been cultured for at least about 8 weeks (“at least 12 weeks” of claim 7 and “about 12 weeks to 24 weeks” of claim 8 each include culturing for 8 weeks or more).
Regarding claim 10, further to the discussion of claims 1 and 9 above, U.S. Co-pending App ‘858 claims the hSCO has been cultured for about 12 weeks to 24 weeks which is encompassed by the claimed range of “about 8 weeks to about 28 weeks” due to the breadth of the term “about.” Additionally, U.S. Co-pending App ‘858 claims the hSCO has been cultured for “at least 12 weeks” (claim 7) and “about 12 weeks to 24 weeks” (claim 8) which overlap or lie within the claimed range of culturing for about 8 weeks to about 28 weeks and thereby make it obvious. Finally, the limitation of “has been culture for about 8 weeks to about 28 weeks” is product-by process language. Since merely culturing on its own does not impart a structure, this is already met by the organoid as claimed by U.S. Co-pending App ‘858 in view of Skibinski.
Since the instant application claims are anticipated by or obvious over cited application claims, in view of Skibinski, said claims are not patentably distinct.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-8 of copending application No. 18/735,858 (claim set filed 5th, June, 2026) in view of Skibinski et al. (WO 2023/220453 A2; published internationally 16th, November, 2023 with priority to U.S. Provisional Application No. 63/342,007 filed 13th, May, 2022; henceforth “Skibinski”) as applied to claim 1 above, and in further view of Fitch et al. (Exp Neurol . 2008 Feb;209(2):294-301. Epub 2007 May 31.; henceforth “Fitch”).
The teachings of U.S. Co-pending App ‘858 and Skibinski above are incorporated herein in their entirety.
Regarding claim 11, further to the discussion of claim 1 above, although U.S. Co-pending App ‘858 claims the hSCO has received an injury (mechanically injured) and comprises glial scar-like tissue as a result of the injury (claim 1), U.S. Co-pending App ‘858 does not claim the organoid has chondroitin sulfate proteoglycans (CSPGs) chondroitin sulfate proteoglycans (CSPGs).
Nevertheless, regarding claim 11, Fitch teaches that chondroitin sulfate proteoglycans are present as a response to injury and glial scar (see “Chondroitin sulfate proteoglycans are found in the brain after stab wound, in the spinal cord after injury to the dorsal root, and in the spinal cord following injury” pg. 296 col. 1). Fitch teaches reactive astrocytes within glial scar have been shown to upregulate chondroitin sulfate proteoglycans (pg. 295 col. 2).
Therefore, regarding claim 11, it would have been obvious to a person of ordinary skill in the art that the organoid as claimed by U.S. Co-pending App ‘858 in view of Skibinski, which includes glial scar and reactive astrocytes and has undergone an injury, would comprise chondroitin sulfate proteoglycans because Fitch teaches this is an expected result of neural tissue undergoing an injury and having glial scar.
Since the instant application claims are anticipated by or obvious over cited application claims, in view of Skibinski, and in further view of Fitch, said claims are not patentably distinct.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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