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 status
Preliminary amendment to the claims filed 12/18/2023 is acknowledged.
Claims 9, 13-20, 30-58 is/are cancelled. Claims 1-8, 10-12, 21-29 is/are currently pending and is/are under examination.
Claim Objections
Claim 23, 26 and 29 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 21, 24 and 27 respectively.
First, it must be noted that neural cells, neuron cells, neuronal cells and neurons are synonyms well known in the art.
Claim 23 limits neural cells of claim 1 to cortical neuron cells. Similarly, claim 21 limits neural cells/neurons of claim 1 to comprise cortical cells i.e. neural cells/neurons of claim 21 are also cortical neuron cells. Thus, claims 21 and 23 are duplicates with the exact same claim scope.
Claim 26 limits neural cells of claim 1 to spinal neuron cells. Similarly, claim 24 limits neural cells/neurons of claim 1 to comprise spinal cells i.e. neural cells/neurons of claim 24 are also spinal neuron cells. . Thus, claims 24 and 26 are duplicates with the exact same claim scope.
Claim 29 limits neural cells of claim 1 to hippocampal neuron cells. Similarly, claim 27 limits neural cells/neurons of claim 1 to comprise hippocampal cells i.e. neural cells/neurons of claim 27 are also hippocampal neuron cells. Thus, claims 27 and 29 are duplicates with the exact same claim scope.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
Claims 7, 10-12 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7 recites “use of papain”, a digestive enzyme, in the purification step of claim 1. It is unclear how a digestive enzyme such as papain could purify neural cells/neurons from brain extracts and how it is being “used” in the said claim. The specification recites embodiments wherein “the purifying step comprises use of papain”, such as on page 6, lines 13-14; page 8, lines 24-25; embodiment #8, 70. However, the examples provided use papain for the dissociation step. See example 1 on page 25, lines 19-22; page 29, lines 5-16. See example 2, step #5. The purification steps appear to involve myelin removal, RBC and debris removal and finally negative selection using an Non-neuronal cells Biotin antibody cocktail (page 25, last para -page 26). The purification steps in the examples provided do not involve enzymatic digestion. Thus, even in light of the specification, it is unclear how papain is used in the purification step. For the purpose of compact prosecution, the claim(s) 7 is/are interpreted as “wherein the dissociation step comprises use of papain”.
Claims 10-12 each recite “wherein the neural cells comprise adult animal cells”, further limiting adult animals cells to “young adult”, “middle-aged adult” or “senior adult” animal cells respectively. Neither the claims nor the specification define these terms. Although “an adult animal” would generally be considered at least reproductively mature, no such clear phenotypic characterization is known for middle-age or senior across animal species such that these age groups could be demarcated. Furthermore, the specification provides exemplary age ranges for various animal species but in each species a young adult animal comprises animals with an age of 0 years (see Table 1, page 6). Animals as young as 0 years could not be considered “adult” or “young adult” in any animal species. Thus, the metes and bounds of terms “adult”, “young adult”, “middle-age” and “senior” are indefinite. Based on the age ranges mentioned in the specification in Table 1, for the purpose of compact prosecution, at least claim(s) 10 is/are interpreted such that an animal of 0 years of age meets the limitations in this claim.
Claim Rejections - 35 USC § 112(d)
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.
Claims 8, 22, 25, and 28 are 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.
Regarding claim 8, claim 1 is directed to a method of processing neural cells wherein the neural cells are explicitly derived from “brain components” of an animal. In other words, claim 1 is directed to a method of processing neural cells that are directly isolated from a living tissue i.e. neural cells of claim 1 are inherently primary cells. Thus, claim 8 merely recites an inherent property of neural cells of claim 1 and does not further limit claim 1.
Claim 22 recites “wherein the neural cells comprise cortical astrocyte cells”. Thus, claim 22 broadens claim 1 which is limited to neural cells i.e. neurons and thus excludes glial cells such as astrocytes. Similarly, claims 25 and 28 also broaden the neural cells 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.
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.
Claim(s) 1-8, 10, 11, 21-29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schroeter et al (One Brain—All Cells: A Comprehensive Protocol to Isolate All Principal CNS-Resident Cell Types from Brain and Spinal Cord of Adult Healthy and EAE Mice. Cells 2021, 10, 651. IDS 12/18/2023) as evidenced by Data Sheet, Adult Brain Dissociation Kit, mouse, and rat (Miltenyi Biotec), Bosio et al (US 2013/0316373 A1, Nov. 28, 2013) and Data Sheet, Neural Tissue Dissociation Kits (P) and (T) (Miltenyi Biotec).
Regarding claims 1 and 8, Schroeter discloses a method for purifying neurons from cell suspension derived from whole brain tissue and spinal cord (2.3.1. Dissection of the CNS; Figure 1). Schroeter’s method comprises dissecting (=claimed extracting) whole brain tissue and spinal cord (=claimed brain component) from mice, then dissociating cells from the dissected tissue using a commercially available kit called “Adult Brain Dissociation Kit, mouse, and rat (Miltenyi Biotec, Bergisch Gladbach, NRW, Germany)” (2.3.2. CNS Tissue Dissociation), followed by purifying neurons from cell suspension (Table 2; Figure 5) and finally culturing the isolated neurons (Table 3; 2.5. Cultivation of Isolated CNS-Resident Cells; Figure 6).
Regarding claim 2, Schroeter discloses a dissociation step which comprises both enzymatic dissociation (see evidentiary use of Enzyme P in Data sheet for Adult Brain Dissociation Kit protocol) and mechanical dissociation using gentleMACS Octo Dissociator (2.3.2. CNS Tissue Dissociation).
Regarding claims 3-5, Schroeter discloses purification that comprises removal of myelin, debris and RBCs (2.3.3. Debris and Red Blood Cell Removal).
Regarding claim 6, Schroeter discloses purification that comprises separating glial cells from neurons using negative selections scheme (Table 2).
Regarding claim 7, in view of 112b issue noted above, Schroeter’s discloses use of the commercially available kit called “Adult Brain Dissociation Kit, mouse, and rat” from Miltenyi Biotec. The Data sheet for this kit evidence use of an “Enzyme P” (see Components on page 1). Bosio is a patent application from Miltenyi Biotech which evidences that Enzyme P in their kits is papain. See Bosio’s disclosure in [0087] stating “dissociated with a trypsin or papain based procedure using the MACS® Neural Tissue Dissociation Kit (T) (NTDK (T)) or the MACS® Neural Tissue Dissociation Kit (P) (NTDK (P)) (Miltenyi Biotec)” and Data sheet for these kits that evidence that Neural Tissue Dissociation Kit (P) also identifies papain as “Enzyme P”. Thus, in using Miltenyi’s Adult Brain Dissociation Kit, Schroeter’s discloses use of papain in their method.
Regarding claim 10, 11, in view of 112b issue noted above, Schroeter discloses dissecting brain tissue from mice that are 10-20 week old (=2.5-5 months = 0.2-0.4 years = at least young and middle age mice) (2.1. Mice).
Regarding claim 21-23, 27-29, Schroeter discloses extracting whole brain tissue from mice for their method which comprises both the cortical and the hippocampal regions (2.3.2. CNS Tissue Dissociation). Thus, Schroeter discloses cells comprising cortical cells, cortical astrocytes, cortical neurons, hippocampal cells, hippocampal astrocytes and hippocampal neurons (Table 1, 2).
Regarding claim 24-26, Schroeter discloses extracting tissue from spinal cord for their method and thus discloses spinal cells, spinal astrocytes and spinal neurons (2.3.2. CNS Tissue Dissociation)
Therefore, Schroeter anticipates the claimed method.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schroeter as applied to claims 1, 10 and 11 above, and further in view of Eide et al (Culture of adult mouse neurons, Biotechniques, 2005 Jan; 38(1); IDS 7/7/2025).
The teachings from Schroeter as detailed in the U.S.C. 102 rejection above are pertinent and relied upon for the instant rejection.
Schroeter discloses the claimed method of claim 1 and further discloses using brain tissue from adult mice 10-20 weeks of age (2.1. Mice).
As noted in the U.S.C. 112b rejection above, the terms “young adult”, “middle-aged adult” and “senior adult” are indefinite. However, to expedite prosecution, the age-range for “young adult”, “middle-aged adult” and “senior adult” mice noted in Table 1 of the instant specification is used for this rejection. Based on the age-ranges noted in Table 1, Schroeter discloses “young adult”, “middle-aged adult” mice (10-20 week old = 2.5-5 months = 0.2-0.4 years = at least young and middle age mice) (2.1. Mice).
Schroeter does not teach “senior adult” mice. However, dissecting brain tissue and dissociating cells from adult mice of 1.5 years of age was known in the art.
Eide taught dissecting brain tissue and dissociating brain cells, including neurons, using papain-based method from adult mice of 1.5 years of age (= “senior adult”; Isolation of Neurons; Attachment of Isolated Brain cells; Figures 4, 5).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use Schroeter’s method to isolate neurons from “senior adult” mice. An ordinary artisan would be motivated to use Schroeter’s method to isolate neurons from “senior adult” mice because Schroeter’s method allows for isolation of neurons only and removal of other cell types from the dissociated cells (Table 2; Figure 5), thus allowing for investigating neurons only from the brains of “senior adult” mice. An ordinary artisan would reasonably expect to apply Schroeter’s method to isolate neurons from “senior adult” mice because papain-based brain tissue dissociation methods had already been applied to senior adult mouse brains, as taught by Eide.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
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