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 August 26, 2025.
Amendments
Applicant's response and amendments, filed September 6, 2023, to the prior Office Action is acknowledged. Applicant has cancelled Claims 1-52, amended Claims 53, 60, and 66.
Claims 53-68 are pending.
Election/Restrictions
Applicant has elected with traverse the invention of Group I, Claims 53-58 and 60-67, drawn to a population of modified primary human B cells in which the variable regions of light and heavy chains of an endogenous B cell receptor have been substituted with variable regions of a heterologous light and heavy chains of a heterologous therapeutic antibody, classified in C12N 2510/02.
Within Group I, Applicant has elected the following species, wherein:
i) the alternative therapeutic monoclonal antibody target is TNFalpha, as recited in Claims 57 and 66; and
ii) the alternative engineered nuclease is Cas9, generically recited in Claim 56, specific embodiments disclosed in [0007, 63].
Response to Arguments
Applicant argues that regardless of the diseases, disorders, and/or conditions to be treated with the claimed product, the claimed process is the same: the product is administered to a patient, per Group II.
Applicant’s argument(s) has been fully considered, but is not persuasive. MPEP §803 states that "If the search and examination of all the claims in an application can be made without serious burden, the examiner must examine them on the merits, even though they include claims to independent or distinct inventions."
In the instant case a serious burden exists since a search of genetic modification of primary human B cells requires a separate, divergent, and non co-extensive search and examination of the as it relates to methods of immunotherapy treatments. Further, a search and examination of all the claims involves different considerations of novelty, obviousness, written description, and enablement for each claim. In view of these requirements, it is the Examiner's position that searching and examining all of the claims in the same application presents a serious burden on the Examiner for the reasons given above and in the previous Restriction Requirement.
Applicant argues that the product could be used in in vitro methods of measuring an immune response, detection assays, etc, is not germane because the Group II method is directed to administering the cells to a patient.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant’s argument is not on point. As stated in the prior Office Action, the Group I product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h).
Applicant argues that in order to be prior art disclosing the claimed method, the cells used in the method first have to exist.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant’s argument is not on point. The issue is that prior art teaching the Group I product does not necessarily lead to prior art teaching the Group II method. Further, a search and examination of all the claims involves different considerations of novelty, obviousness, written description, and enablement for each claim. In view of these requirements, it is the Examiner's position that searching and examining all of the claims in the same application presents a serious burden on the Examiner for the reasons given above and in the previous Restriction Requirement.
The requirement is still deemed proper and is therefore made FINAL.
As discussed in the prior Office Action, the Group II method is subject to rejoinder when the Group I product is found allowable. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claims 53-68 are pending.
Claims 59 and 68 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 53-58 and 60-67 are under consideration.
In light of the cited prior art below, the Examiner withdraws the antibody target molecule species election between elected TNFalpha and CD4, CEA, influenza, hepatitis C, HER2, HIV, MUC1, Staphylococcus aureus, and Rhesus factor.
Priority
This application is a continuation of application 15/161,213 filed on May 21, 2016, now abandoned, which is a continuation-in-part of PCT/US2016/025920 filed on April 4, 2016. Applicant’s claim for the benefit of a prior-filed application provisional application 62/142,882 filed on April 3, 2015 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
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 application, Application No. 62/142,882, fails 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.
‘882 disclosure is silent to the limitations recited in instant Claims 61 and 64-65.
Support for Claims 61 and 64-65 may be found in PCT/US2016/025920 filed on April 4, 2016.
Accordingly, the effective priority date of Claims 61 and 64-65 is April 4, 2016.
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
1. Applicant has not filed any Information Disclosure Statements with the instantapplication.
The Examiner cites below reference previously cited in Applicant’s co-pending application, e.g. 15/161,213 and 17/687,246, and/or cited in Applicant’s parent application IDS, e.g. 16/152,273, to wit:
Wang et al (RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection, PNAS 111(36): 13157-13162, available online August 25, 2014); and
Mandal et al (Efficient Ablation of Genes in Human Hematopoietic Stem and Effector Cells using CRISPR/Cas9, Cell Stem Cell 15: 643-652; available online November 6, 2014).
Applicant is reminded of their duty to disclose information material to patentability. See MPEP §2001 and 37 C.F.R. 1.56.
The individuals covered by 37 CFR 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question. As set forth by the court in Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972):
[W]e think that it is unfair to the busy examiner, no matter how diligent and well informed he may be, to assume that he retains details of every pending file in his mind when he is reviewing a particular application . . . [T]he applicant has the burden of presenting the examiner with a complete and accurate record to support the allowance of letters patent.
See MPEP §2001.06(b).
Pursuant to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.), a copy of the prior cited publication(s) are not provided with the instant Office Action because it is presumed that Applicant has a copy of the prior-cited publication(s), as such is routine practice in the art, and as evidenced by 16/152,273, and that Applicant has provided their representative with a copy of said publication(s) to establish a prosecution record.
However, if Applicant’s representative insists upon receiving a copy of the entire references, then the Examiner will make attempts to provide it in the next Office Action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
2. Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification (e.g. [000154, 156-159, 227-230, 234-235, 237-238, 263-266]) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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(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.
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.
3. Claims 54-55 and 62-65 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 53 is directed to a primary human B cell whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody.
Claim 60 is directed to a primary human B cell whose genome has been gene-edited to insert variable regions of light and heavy chains of a heterologous therapeutic antibody.
Claims 54 and 62-65 recite the limitation “transfected”. There is insufficient antecedent basis for this limitation in the claims because the claims suffer from a dangling modifier, failing to recite the object which is to be transfected into the primary human B cells of the independent claims.
4. Claims 54-55 and 62-65 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.
Claim 53 is directed to a primary human B cell whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody.
Claim 60 is directed to a primary human B cell whose genome has been gene-edited to insert variable regions of light and heavy chains of a heterologous therapeutic antibody.
Claims 54 and 62-65 recite the limitation “transfected”.
Such limitations fail to further limit the structure(s) of the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims.
The recitation of a process limitation in Claims 54-55 and 62-65 is not viewed as positively limiting the claimed product of Claims 53 and 60 absent a showing that the process of making recited in the dependent claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The method in which the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
There is no objective evidence that genome-edited primary human B cells comprising the claimed gene-edits [structures] made via transfection to introduce the heterologous nucleic acids are molecularly distinguishable from genome-edited primary human B cells comprising the claimed gene-edits [structures] made via other means of introducing the heterologous nucleic acids, e.g. electroporation, nucleofection, or transduction.
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.
5. Claim 56 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 53 is directed to a primary human B cell whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody.
Claim 56 recites wherein substitution of the light and heavy chains of the endogenous B cell receptor is accomplished using an engineered nuclease.
There is insufficient antecedent basis for “substitution of the light and heavy chains of the endogenous B cell receptor” limitation in the claims because Applicant cancelled prior recitation of a substitution of an endogenous B cell receptor, and instead broadened the scope of the insertion to be anywhere in the B cell’s genome.
6. Claims 58 and 67 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 58 and 67 recite the limitation “can be administered to a patient”.
Either this is an inherent property of (that naturally flows from) the population of genome-edited primary human B cells comprising the claimed genome-edits [structures] of independent Claims 53 and 60, respectively, or it is not, and something [structure] of the cells of the independent claims must change.
To the extent it is an inherent property of (that naturally flows from) the product of the independent claim, then the instant claims fails to further limit the independent claims, respectively.
Furthermore, in regard to instant claims, it is noted that the "can be administered to a patient" clause does not recite any additional structures, but simply states a characterization of the cells of the independent claims. 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.").
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase “can be administered to a patient” is an intended use limitation, which does not contain any further structural limitations with respect to claimed primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims (see MPEP §2114).
The claims fail to recite, and the specification fails to disclose, a first population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are not “transplantable…”, as opposed to a second population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are “transplantable…”.
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.
7. Claim(s) 58 and 67 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 58 and 67 recite the limitation “can be administered to a patient”.
Either this is an inherent property of (that naturally flows from) the population of genome-edited primary human B cells comprising the claimed genome-edits [structures] of independent Claims 53 and 60, respectively, or it is not, and something [structure] of the cells of the independent claims must change.
The claims denote that not all populations of the genome-edited primary human B cells having the claimed genome-edits [structures] of the independent claims, respectively, are “transplantable” [function].
To the extent it is not an inherent property of (that naturally flows from) the product of the independent claim, then the instant claims fails lack adequate written description for failing to recite the required structural change(s) that transforms a first population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are not “transplantable…”, as opposed to a second population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are “transplantable…”.
Furthermore, in regard to instant claims, it is noted that the "can be administered to a patient" clause does not recite any additional structures, but simply states a characterization of the cells of the independent claims. 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.").
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
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, a first population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are not “transplantable…”, as opposed to a second population of genome-edited primary human B cells comprising the claimed genome-edits [structures] which are “transplantable…”.
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)
8. Claim(s) 65 is 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim recites wherein at least 50%, 60%, 70%, 75%, or 80% of the primary B cells are viable after transfection.
The claim appears to be drafted in Product-by-Process form.
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 claim denotes that not all transfection steps will necessarily and predictably yield at least 50%, 60%, 70%, 75%, or 80% of the primary B cells are viable after transfection.
The claim is considered to lack adequate written description because the claim fails to recite the required nexus between the transfection means [structure/method step] and the resulting post-transfection % viability [function].
The claim fails to recite, and the specification fails to disclose, a first transfection step that, while capable of yielding at least 5% viability of the primary B cells after transfection, is unable to achieve at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection, as opposed to
a second transfection step that, while capable of yielding at least 10% viability of the primary B cells after transfection, is unable to achieve at least 20%, 30%, 40%, 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection, as opposed to
a third transfection step that, while capable of yielding at least 20% viability of the primary B cells after transfection, is unable to achieve at least 30%, 40%, 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection, as opposed to
a fourth transfection step that, while capable of yielding at least 30% viability of the primary B cells after transfection, is unable to achieve at least 40%, 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection, as opposed to
a fifth transfection step that, while capable of yielding at least 40% viability of the primary B cells after transfection, is unable to achieve at least 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection, as opposed to
a sixth transfection step that necessarily and predictably achieves at least 50%, 60%, 70%, 75%, or 80% viability of the primary B cells after transfection.
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)
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
9. Claim(s) 53-55 and 57-58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jolly et al (U.S. 2004/0156832).
With respect to Claim 53, Jolly et al is considered relevant prior art for having disclosed an isolated human B cells (e.g. [0033], lymphocytes, as opposed to lymphocyte cell lines), comprising one or more genomic modifications, wherein said genomic modification comprises inserting a nucleic acid sequence encoding an exogenous antibody [0012, 34-35], wherein the antibody is a therapeutic antibody (e.g. Abstract; [0184]).
With respect to Claims 54-55, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
The recitation of a process limitation in Claims 54-55 is not viewed as positively limiting the claimed product of Claim 53 absent a showing that the process of making recited in the dependent claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The method in which the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
With respect to Claim 57, Jolly et al disclosed an antibody specific for Rhesus Factor (e.g. Examples 4-9).
With respect to Claim 58, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase “can be administered to a patient” is an intended use limitation, which does not contain any further structural limitations with respect to claimed primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims (see MPEP §2114).
Thus, Jolly et al anticipate the claims.
10. Claim(s) 53-55 and 57-58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scholz et al (U.S. 2013/0143267).
With respect to Claim 53, Scholz et al is considered relevant prior art for having disclosed and successfully demonstrated the ability of the ordinary artisan to genetically modify resting B cells, including primary human B cells (e.g. [0022], “a source of B cells is obtained from a subject”, “Examples of subjects include humans”), to express a transgene of interest, wherein the transgene of interest is a therapeutic monoclonal antibody (e.g. [(0076, 87], b12 anti-HIV-1 neutralizing antibody; Example |, primary human B cells transduced to successfully produce the HIV neutralizing antibody b12).
With respect to Claims 54-55, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
The recitation of a process limitation in Claims 54-55 is not viewed as positively limiting the claimed product of Claim 53 absent a showing that the process of making recited in the dependent claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The method in which the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
With respect to Claim 57, Scholz et al disclosed an antibody specific for CD4, CEA, HER2, HIV, or MUC1 (e.g. [0076, 84-85]).
With respect to Claim 58, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase “can be administered to a patient” is an intended use limitation, which does not contain any further structural limitations with respect to claimed primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims (see MPEP §2114).
Thus, Scholz et al anticipate the claims.
11. Claim(s) 53-55 and 57-58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hyde et al (U.S. 2013/0164277).
With respect to Claim 53, Hyde et al is considered relevant prior art for having disclosed primary human B cells whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody (e.g. [0116]).
With respect to Claims 54-55, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
The recitation of a process limitation in Claims 54-55 is not viewed as positively limiting the claimed product of Claim 53 absent a showing that the process of making recited in the dependent claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The method in which the primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Nevertheless, Hyde et al disclosed and successfully demonstrated the ability to transfect primary B cells with a nucleic acid encoding an immunoglobulin molecule (e.g. [0045, 47, 49], “transfected with”).
With respect to Claim 57, Hyde et al disclosed an antibody specific for influenza, hepatitis C, Staphylococcus aureus (e.g. [0042, 112]; Examples 2 and 6).
With respect to Claim 58, the claims fail to further limit the cells of Claim 53. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, above.
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase “can be administered to a patient” is an intended use limitation, which does not contain any further structural limitations with respect to claimed primary human B cell(s) whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody recited in the independent claims (see MPEP §2114).
Thus, Hyde et al anticipate the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
12. Claims 53-55, 57-58, and 60-67 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Hyde et al (U.S. 2013/0164277; of record) in view of Ando et al (U.S. 2008/0159996), Gregory et al (U.S. 2014/0301990; priority to March 21, 2013), and Zhang et al (U.S. 2014/0179770; filed December 12, 2013).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 53, Hyde et al is considered relevant prior art for having disclosed primary human B cells whose genome comprises a nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody (e.g. [0116]).
Hyde et al do not disclose wherein the nucleic acid sequence encoding the variable regions of light and heavy chains of a heterologous therapeutic antibody is introduced into the genome of the primary human B cell via gene-editing.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 60, Ando et al is considered relevant prior art for having disclosed the use of site-specific nucleases, e.g. zinc finger nucleases [0007-14], to introduce the artisan’s heterologous nucleic acid of interest into the host cell’s targeted genomic locus [0017], wherein the host cell is primary B lymphocytes, e.g. peripheral blood mononuclear cells [0016, 122].
Similarly, Gregory et al is considered relevant prior art for having disclosed the use of ZFN, TALEN, or CRISPR/Cas system [0015, 21] to introduce the artisan’s heterologous nucleic acid of interest into the host cell’s targeted genomic locus, wherein the host cell is primary lymphocytes (PBMCs), which inherently and naturally comprise primary B cells and primary T lymphocytes [0184].
Zhang et al is considered relevant prior art for having disclosed the use of CRISPR/Cas9 system [0010-11] to modify the genome of the target host cell with a heterologous nucleic acid encoding the artisan’s protein of interest [0065], wherein the target host cell includes B cells [0261], including primary human B cells [0262, 566].
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, gene editing technologies, and the creation of genetically modified cells. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first means of introducing nucleic acid sequences encoding heavy and light chain variable regions of a therapeutic antibody into primary human B cells, as disclosed by Jolly et al, with a second means, to wit, using gene-editing technologies such as the ZFN, TALEN, or CRISPR/Cas system, as disclosed by Ando et al, Gregory et al, and Zhang et al, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one