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 .
Detailed Action
This action is in response to the papers filed September 27, 2023.
Claims 1-17 are pending and under consideration.
Priority
This application is a continuation of application 16/839,906 filed April 3, 2020, now abandoned, which is a continuation of application 15/565,922 filed on October 12, 2017, now abandoned, which is a 371 of PCT/JP2016/062040 filed on April 14, 2016.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d).
While a certified copy of the foreign patent application JP 2015-082768 filed on April 14, 2015 and PCT/JP2016/062040 filed on April 14, 2016 are provided in parent application 15/565,922, a certified English translation of said foreign patent applications have not been provided.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed applications, 16/839,906 filed April 3, 2020, 15/565,922 filed on October 12, 2017, PCT/JP2016/062040 filed on April 14, 2016, and JP 2015-082768 filed on April 14, 2015 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claim 1 recites a secondary stem cell comprising:
a) about 7 to about 26 copies of an exogenous c-Myc gene; and
about 1 to about 6 copies of an exogenous Bmi1 gene; or
b) a ratio of 2:1 to 7:1 of an exogenous Bmi1 gene to an exogenous c-Myc gene.
As discussed above, while a certified copy of the foreign patent application JP 2015-082768 filed on April 14, 2015 is provided in parent application 15/565,922, a certified English translation of said foreign patent application has not been provided. There is no clear support for the instant recitation in JP 2015-082768.
PCT/JP2016/062040 filed on April 14, 2016 is also in Japanese, not English. A certified English translation of said foreign patent application has not been provided. There is no clear support for the instant recitation in PCT/JP2016/062040.
While the 15/565,922 specification discloses secondary iPS cell clones comprising a ratio of 3:1 to 5:1 of an exogenous Bmi1 gene to an exogenous c-Myc gene (e.g. Table 1), as recited in Claim 2, instant recitation is far broader in scope than that disclosed in ‘922 Table 1. Neither the specification, drawings, or originally filed claims disclose a Bmi1:Myc ratio of 2:1, 6:1, or 7:1. At best, the ratio is 3:1 to 5:1, as recited in Claim 2.
While the 15/565,922 drawings disclose the relative numbers of exogenous Bmi1 genes and an exogenous c-Myc genes in secondary iPS cell clones (e.g. Figure 4b), instant recitation is opposite of that disclosed in ‘922 Figure 4b.
Instant claims are recited at a high level of generality, and do not recite nor require the respective Myc vector and/or Bmi1 vector to be lentiviral vectors, retroviral vector, or even viral vectors. Instant claims are broader in scope than the c-Myc lentiviral vector and the Bmi1 lentiviral vector.
16/839,906 filed April 3, 2020 and instant application, being continuations, suffer the same deficiencies as 15/565,922.
Accordingly, the effective priority date of the instant claims is granted as September 27, 2023, the filing date of the instant application.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on September 27, 2023 that has been considered.
The information disclosure statement filed September 27, 2023 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
NPL citation 16 has been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
Claim Objections
1. Claim 1 is objected to because of the following informalities:
Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m).
Embodiments (a) and (b) should be separated by line indentation.
Appropriate correction is required.
2. Claim 12 is objected to because of the following informalities:
As a first matter, the phrase “copies the exogenous Bmi1 gene” (line 1) is missing its preposition. See, for example, “copies of the exogenous c-Myc gene” (Claim 12, line 2).
As a second matter, the phrases “copies” are missing the article “the” prior to “copies”, as in ‘the copies’.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
New matter
3. Claim(s) 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a secondary stem cell comprising:
a) about 7 to about 26 copies of an exogenous c-Myc gene; and
about 1 to about 6 copies of an exogenous Bmi1 gene; or
b) a ratio of 2:1 to 7:1 of an exogenous c-Myc gene to an exogenous Bmi1 gene.
Claim 9 recites dependency upon Claim 1.
Clear support for the new limitation(s) cannot be found in the instant application or priority documents. Accordingly, the amendment(s) to Claim(s) 1 is considered to constitute new matter.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application”. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
As discussed above, while a certified copy of the foreign patent application JP 2015-082768 filed on April 14, 2015 is provided in parent application 15/565,922, a certified English translation of said foreign patent application has not been provided. There is no clear support for the instant recitation in JP 2015-082768.
PCT/JP2016/062040 filed on April 14, 2016 is also in Japanese, not English. A certified English translation of said foreign patent application has not been provided. There is no clear support for the instant recitation in PCT/JP2016/062040.
While the 15/565,922 specification discloses secondary iPS cell clones comprising a ratio of 3:1 to 5:1 of an exogenous Bmi1 gene to an exogenous c-Myc gene (e.g. Table 1), instant recitation is far broader in scope than that disclosed in ‘922 Table 1. Neither the specification, drawings, or originally filed claims disclose a BMI:Myc ratio of 2:1, 6:1, or 7:1. At best, the ratio is 3:1 to 5:1.
While the 15/565,922 drawings disclose the relative numbers of exogenous Bmi1 genes and an exogenous c-Myc genes in secondary iPS cell clones (e.g. Figure 4b), instant recitation is opposite of that disclosed in ‘922 Figure 4b.
Instant claims are recited at a high level of generality, and do not recite nor require the respective Myc vector and/or Bmi1 vector to be lentiviral vectors, retroviral vector, or even viral vectors. Instant claims are broader in scope than the c-Myc lentiviral vector and the Bmi1 lentiviral vector.
16/839,906 filed April 3, 2020 and instant application, being continuations, suffer the same deficiencies as 15/565,922.
If applicant believes the earlier applications provide support for this disclosure, applicant must point out such support with particularity by page and line number in the reply to this Action.
Applicant fails to articulate where support for such amendments are to be found in the instant specification, let alone parent applications 15/565,922, PCT/JP2016/062040 filed on April 14, 2016, and JP 2015-082768 filed on April 14, 2015.
The specification discloses, for example, that primary megakaryocyte progenitor cells were transfected with plasmids encoding the oncogene c-Myc and the polycomb gene BMI1 [0084], whereupon it was found that in 10 secondary iPS cell clones obtained by said method, about 7-26 copies of exogenous c-Myc inserts and about 1-6 copies of exogenous BMI1 inserts were present in said secondary stem cell clones [0085].
Such does not support the instantly recited claims.
Alternatively, if Applicant believes that support for the method step of introducing into the secondary stem cell chromosomes about 7 to about 26 copies of a c-Myc gene and about 1 to about 6 copies of an a Bmi1 gene is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must, in responding to this Office Action, point out with particularity, where such support may be found.
Similarly, if Applicant believes that support for a BMI:Myc ratio of 2:1, 6:1, or 7:1 is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must point out such support with particularity by page and line number in the reply to this Action.
Similarly, if Applicant believes that support for the broadly genus of vectors to yield presently recited exogenous gene copy numbers and relative ratios is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must point out such support with particularity by page and line number in the reply to this Action.
Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
4. Claim(s) 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a secondary stem cell comprising:
about 7 to about 26 copies of an exogenous c-Myc gene; and
about 1 to about 6 copies of an exogenous Bmi1 gene; or
a ratio of 2:1 to 7:1 of an exogenous c-Myc gene to an exogenous Bmi1 gene.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, the structure/method step nexus between how the exogenous Bmi1 and c-Myc genes are introduced into the host cell, including secondary stem cells, so as to necessarily and predictably achieve a Bmi1/Myc ratio of 3:1, as opposed to 2:1, 1:1, 0.5:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc…
While the specification discloses the step of introducing cMyc and Bmi1 transgenes into hematopoietic progenitor cells using lentiviral vectors (e.g. [0075]), the working examples are obfuscatory, failing to disclose the actual dosage or amounts of said lentiviral vectors encoding the cMyc and Bmi1 transgenes, respectively, and/or in combination. Mere reference to infecting 293T producer cells with lentivirus vectors at MOI 300 does nothing to inform the ordinary artisan as to the actual dosage or amounts of said lentiviral vectors encoding the cMyc and Bmi1 transgenes, respectively, and/or in combination used to transfect the hematopoietic progenitor cells.
As discussed above, neither the specification, drawings, or originally filed claims of the parent and foreign priority applications disclose a Bmi1:Myc ratio of 2:1, 6:1, or 7:1.
At best, the ratio is 3:1 to 5:1.
The working example discloses the steps of:
culturing the genetically modified cells for at least two weeks (14 days) [0076],
then transducing with a lentivirus vector expressing Bcl-XL [0076], t
then culturing for an indeterminate amount of time,
then culturing the cells at low density in a 96-well plate for at least two weeks (14 days) [0077],
then growing up each particular sub-pool for an indeterminate amount of time [0077],
then culturing the cells for 7 days, and analyzing platelet production [0078], Round 1,
then selecting those clones with a platelet production volume that is about 1.6 to 1.9 times greater than a control megakaryocyte progenitor cell [0079], and
then performing second and third rounds of selection on the first-selected set of clones [0080-81].
Thus, it appears that the instantly recited properties are dependent upon multiple variables, not just the dosage/amount of the respective Myc vector and/or Bmi1 vector.
Note that instant claims are recited at a high level of generality, and do not recite nor require the respective Myc vector and/or Bmi1 vector to be lentiviral vectors, retroviral vector, or even viral vectors.
The specification does not support the use of non-lentiviral or non-retroviral vectors with which to introduce the Myc and Bmi1 transgenes into the host cells so as to thereby necessarily and predictably yield:
a Bmi1:Myc ratio of 2:1, 3:1, 4:1, 5:1, 6:1, or 7:1;
about 7 to about 26 copies of an exogenous c-Myc gene and about 1 to about 6 copies of an exogenous Bmi1 gene; nor
about 7 to about 26 copies of an exogenous Bmi1 gene and about 1 to about 6 copies of an exogenous c-Myc gene.
Nakamura et al (Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells. Cell Stem Cell 14(4): 535-548, 2014; available online February 13, 2014; Applicant’s own work, of record in IDS) is considered relevant prior art for having taught the step of transducing hematopoietic progenitor cells with lentiviral vectors encoding Bmi1 and cMyc transgenes.
However, Nakamura et al is silent to the thus-resulting integrated copies of the Bmi1 transgenes, the cMyc transgenes, and the relative BMI/Myc transgene ratio(s).
Eto et al (U.S. Patent 9,200,254; Applicant’s own work) is considered relevant prior art for having disclosed introducing exogenous Myc and Bmi1 transgenes into megakaryocytic progenitor cells using retroviral vectors (e.g. col. 20, lines 1-25).
However, Eto et al is silent to the thus-resulting integrated copies of the Bmi1 transgenes, the cMyc transgenes, and the relative Bmi1/Myc transgene ratio(s).
Eto et al (U.S. Patent 9,738,906; Applicant’s own work) is considered relevant prior art for having disclosed introducing exogenous Myc and Bmi1 transgenes into megakaryocytic progenitor cells using retroviral vectors (e.g. col. 18, Example 1, lines 58-65).
However, Eto et al is silent to the thus-resulting integrated copies of the Bmi1 transgenes, the cMyc transgenes, and the relative Bmi1/Myc transgene ratio(s).
Either the instantly recited results of a Bmi1:Myc ratio of 2:1 to 7:1, even more specifically, 3:1 to 5:1, is an inherent property that naturally flows from Applicant’s prior reductions to practice of introducing cMyc and Bmi1 transgenes into hematopoietic progenitor cells or megakaryotic progenitor cells using lentiviral or retroviral transduction, or it is not, and something must change in the method of transduction in order to necessarily and predictably achieve the instantly recited ratios.
Either the instantly recited results of about 7 to about 26 copies of an exogenous c-Myc gene and about 1 to about 6 copies of an exogenous Bmi1 gene is an inherent property that naturally flows from Applicant’s prior reductions to practice of introducing cMyc and Bmi1 transgenes into hematopoietic progenitor cells or megakaryotic progenitor cells using lentiviral or retroviral transduction, or it is not, and something must change in the method of transduction in order to necessarily and predictably achieve the instantly recited ratios.
Either the instantly recited results of about 7 to about 26 copies of an exogenous Bmi1 gene and about 1 to about 6 copies of an exogenous cMyc gene is an inherent property that naturally flows from Applicant’s prior reductions to practice of introducing cMyc and Bmi1 transgenes into hematopoietic progenitor cells or megakaryotic progenitor cells using lentiviral or retroviral transduction, or it is not, and something must change in the method of transduction in order to necessarily and predictably achieve the instantly recited ratios.
Instant specification fails to make up for the deficiencies of Applicant’s own prior art.
Roth et al (Mutant MGMT Lentivirus Co-Transduction with a Marker Lentivirus Efficiently Enriches for Dual-Vector Expressing Cells In Vivo, Mol. Therapy 9(Suppl 1): abstract 914, pg S349, 2004; of record in IDS) is considered relevant prior art for having taught co-transduction of mammalian host cells with lentiviral vectors, whereby the two lentiviral vectors were combined at varying ratios for co-transduction. Roth et al taught that the level of expression achieved for each gene was proportional to the amount of the specific virus added.
However, Roth et al is silent regarding the respective copy numbers, nor the relative ratio(s), of the first and second lentiviral vectors integrated into the host cell’s genome.
Wotherspoon et al (Susceptibility of Cell Populations to Transduction by Retroviral Vectors, J. Virol. 78(10): 5097-5102, 2004; of record in IDS) is considered relevant prior art for having taught is considered relevant prior art for having taught co-transduction of mammalian host cells with retroviral vectors, whereby the two retroviral vectors were combined at 9 different ratios varying between 0.3:1 and 24:1 (pg 5098, col. 2, co-transduction of TF-1 cells, PG/LNGFR: PG13/LGFP). Wotherspoon et al taught that transduction with one vector increased the probability of transduction by the second vector (pg 5099, col. 2).
However, Wotherspoon et al is silent regarding the respective copy numbers, nor the relative ratio(s), of the first and second lentiviral vectors integrated into the host cell’s genome.
Lathuiliere et al (Genetic engineering of cell lines using lentiviral vectors to achieve antibody secretion following encapsulated implantation, Biomaterials 35(2): 792-802, January, 2014; of record in IDS) is considered relevant prior art for having taught a host cell co-transduction of a first lentiviral vector encoding a first transgene and a second lentiviral vector encoding a second transgene, the method comprising the steps of varying the relative MOI values of the first and second lentiviral vectors (e.g. Figure 1, MOI 0.2, 0.4, 0.6, 0.8, and 1; Figure 2, MOI 0.5, 1, 1.5, 2, 250, 500, 750, 1000, 1250, and 1500; Figure 3, MOI 50, 150, 300, 500, 1000, and 1500).
Lathuliere et al taught that different target host cells resulted in different transduction efficiencies (e.g. Figure 1 c-d), that the relative ratio of the first transgene to the second transgene varied between 1:1 and 2.4:1 (e.g. Figure 4b), and the relative integrated transgene copy numbers varied from about 40 to 60 copies of a first transgene, and 60 to 100 copies of the second transgene (e.g. Figure 3b).
Shabran et al (Multiplicity of Infection/Multiplicity of Confusion, Molecular Therapy 2(5): 420-421, 2000) is considered relevant prior art for having taught that while MOI is, on its surface, a simple concept, it would be more precise to refer to MOI as a qualitative term that does not truly resemble the experimental conditions (e.g pg 420, col. 1, Introduction). The adjective MOI is not sufficient in the context of a scientific community, and research is a community activity (pg 420, col. 2). For example, if an experiment describes the effects of an MOI of 10 relative to an MOI of 50, one can make some conclusions on the effects of increasing the viral concentration by five. However, no specific information on what those viral concentrations might be can be defined. Therefore, without additional information the experiment would be unreproducible and, under most peer-review criteria, unpublishable. To avoid these confusions all of the significant variables of an infectious protocol most be described. These include virus concentration, infection time duration, and target surface area. The first important bit of information is the titer of the original virus. Interpretation of the infectious titer also requires a full description of all the infection set-up conditions (pg 421, col. 1). The practice of using MOI to describe experimental conditions becomes even more problematic when one wishes to make claims about gene-specific effects (e.g. pg 421, col. 2), in this case the production of secondary stem cells for the production of platelets. Thus, even though as a community we have used the term for many decades, it
is time we reconsider its context and discontinue its use as a quantitative term. As Ralph Waldo Emerson said, “a foolish consistency is the hobgoblin of little minds.” (pg 421, col. 2).
The claims fail to recite, and the specification fails to disclose, how to make secondary stem cells comprising about 5 copies of an exogenous c-Myc gene and about 5 copies of an exogenous Bmi1 gene, as opposed to:
secondary stem cells comprising about 10 copies of an exogenous c-Myc gene and about 15 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 2 copies of an exogenous c-Myc gene and about 7 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 12 copies of an exogenous c-Myc gene and about 6 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 8 copies of an exogenous c-Myc gene and about 3 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 3 copies of an exogenous c-Myc gene and about 7 copies of an exogenous Bmi1 gene; and/or
secondary stem cells comprising about 21 copies of an exogenous c-Myc gene and about 4 copies of an exogenous Bmi1 gene;
etc….
The claims fail to recite, and the specification fails to disclose, how to make secondary stem cells comprising an exogenous Bmi1 gene to an exogenous cMyc gene ratio of 1:1, as opposed to:
2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, and/or 1:10, etc…
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
5. Claims 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The Examiner incorporates herein the above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
6. Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 2 and 12 recite wherein the Bmi1/Myc ratio is 3:1 to 5:1.
Either this is an inherent property of (that naturally flows from) the method of introducing the exogenous Bmi1 and c-Myc genes in order to yield the secondary stem cells of Claims 1 and 9, or it is not, and something must change.
To the extent it is an inherent property of (that naturally flows from) the method by which the cells of Claims 1 and 9 are produced, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the "wherein the Bmi1/Myc ratio is 3:1 to 5:1" clause does not recite any additional structures and/or active method steps, but simply states a characterization or conclusion of the results of cells positively recited in Claim 1 and/or the method of Claim 9. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The Examiner incorporates herein the above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description and enablement rejections.
The claims fail to recite, and the specification fails to disclose, the structure/method nexus between how the exogenous Bmi1 and c-Myc genes are introduced into the host cell, including secondary stem cells, so as to necessarily and predictably achieve a Bmi1/Myc ratio of 3:1, as opposed to 2:1, 1:1, 0.5:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc…
The claims fail to recite, and the specification fails to disclose, how to make secondary stem cells comprising about 5 copies of an exogenous c-Myc gene and about 5 copies of an exogenous Bmi1 gene, as opposed to:
secondary stem cells comprising about 10 copies of an exogenous c-Myc gene and about 15 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 2 copies of an exogenous c-Myc gene and about 7 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 12 copies of an exogenous c-Myc gene and about 6 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 8 copies of an exogenous c-Myc gene and about 3 copies of an exogenous Bmi1 gene;
secondary stem cells comprising about 3 copies of an exogenous c-Myc gene and about 7 copies of an exogenous Bmi1 gene; and/or
secondary stem cells comprising about 21 copies of an exogenous c-Myc gene and about 4 copies of an exogenous Bmi1 gene;
etc….
The claims fail to recite, and the specification fails to disclose, how to make secondary stem cells comprising an exogenous Bmi1 gene to an exogenous cMyc gene ratio of 1:1, as opposed to:
2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, and/or 1:10, etc…
While the specification discloses the step of introducing cMyc and Bmi1 transgenes into hematopoietic progenitor cells using lentiviral vectors (e.g. [0075]), the working examples are obfuscatory, failing to disclose the actual dosage or amounts of said lentiviral vectors encoding the cMyc and Bmi1 transgenes, respectively, and/or in combination. Mere reference to infecting 293T producer cells with lentivirus vectors at MOI 300 does nothing to inform the ordinary artisan as to the actual dosage or amounts of said lentiviral vectors encoding the cMyc and Bmi1 transgenes, respectively, and/or in combination used to transfect the hematopoietic progenitor cells.
As discussed above, neither the specification, drawings, or originally filed claims of the parent and foreign priority applications disclose a Bmi1:Myc ratio of 2:1, 6:1, or 7:1.
At best, the ratio is 3:1 to 5:1.
It appears that the same method step(s) in order to yield the cells of independent Claim 1 necessarily yield the cells of Claim 2, and thus Claim 2 fails to further limit Claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Applicant should cancel Claims 2 and 12, and amend independent Claim 1 to recite a Bmi1:Myc ratio of 3:1 to 5:1.
7. Claims 3 and 13 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.
Claims 1 and 9 recite a secondary stem cell comprising:
a) about 7-26 copies of cMyc and about 1-6 copies of Bmi1; or
b) a Bmi1:cMyc ratio of 2:1 to 7:1.
Claims 3 and 13 recite wherein said secondary stem cell expresses MEG3.
Either this is an inherent property of (that naturally flows from) the secondary stem cells of Claims 1 and 9, or it is not, and something must change.
To the extent it is an inherent property of (that naturally flows from) the secondary stem cells of Claims 1 and 9, then the instant claim fails to further limit the independent claim.
Furthermore, in regard to instant claims, it is noted that the “wherein the secondary stem cell expresses MEG3” clause does not recite any additional structures and/or active method steps, but simply states a characterization or conclusion of the results of cells positively recited in Claim 1 and/or the method of Claim 9. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
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.
8. Claim(s) 3 and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 9 recite a secondary stem cell comprising:
a) about 7-26 copies of cMyc and about 1-6 copies of Bmi1; or
b) a Bmi1:cMyc ratio of 2:1 to 7:1.
Claims 3 and 13 recite wherein said secondary stem cell expresses MEG3.
Either this is an inherent property of (that naturally flows from) the secondary stem cells of Claims 1 and 9, or it is not, and something must change.
To the extent it is not an inherent property of (that naturally flows from) the secondary stem cells of Claims 1 and 9, then the instant claims lack adequate written description for failing to recite the structural and/or method step changes to independent Claims 1 and 9, respectively, necessary and sufficient to yield the functional language recited in Claims 3 and 13.
Furthermore, in regard to instant claims, it is noted that the “wherein the secondary stem cell expresses MEG3” clause does not recite any additional structures and/or active method steps, but simply states a characterization or conclusion of the results of cells positively recited in Claim 1 and/or the method of Claim 9. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Conclusion
9. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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