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 .
It appears the inventor filed the current application pro se (i.e., without the benefit of representation by a registered patent practitioner). While inventors named as applicants in a patent application may prosecute the application pro se, lack of familiarity with patent examination practice and procedure may result in missed opportunities in obtaining optimal protection for the invention disclosed. The inventor(s) may wish to secure the services of a registered patent practitioner to prosecute the application, because the value of a patent is largely dependent upon skilled preparation and prosecution. The Office cannot aid in selecting a patent practitioner.
A listing of registered patent practitioners is available at https://oedci.uspto.gov/OEDCI/. Applicants may also obtain a list of registered patent practitioners located in their area by writing to Mail Stop OED, Director of the U.S. Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450.
In addition, Applicant is encouraged to contact the Application Assistance Unit (AAU), which unit can provide assistance with a broad range of questions and issues. The AAU is available Monday – Friday from 8:30 AM to 5:00 PM (Eastern). AAU contact information: 888-876-0101 (Toll Free) or 571-272-4000 (Local).
Applicant’s reply to the February 17, 2026 Office Action, filed May 22, 2026, is acknowledged. Claims 8, 12, 21, and 23-31 remain withdrawn from consideration, as being drawn to a non-elected invention. Applicant previously canceled claims 13 and 22, and now cancel claims 10, 16, and 19.
Applicant amends claims 1-7, 9, 11, 14-15, 17-18, 20, and 32-37, and withdrawn claim 8. Claim 8 should have the status identifier: “(Withdrawn – Currently Amended).” Claim 15, should have the status identifier “(Currently Amended).” Applicant adds new claims 38-39. Accordingly, claims 1-7, 9, 11, 14-15, 17-18, 20, and 32-39 are under examination. It is noted that the Remarks filed May 22, 2026 contain listings of amendments to the specification and claims, which do not always match the amendments listed in the substitute specification or the actual amended claim set. However, only the amendments set forth in the substitute specification and the actual amended claim set are considered to be entered.
Any objection or rejection of record in the previous Office Action, mailed February 17, 2026, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Priority
This application makes reference to or appears to claim subject matter disclosed in Application No. 16/995,829, filed August 18, 2020. If applicant desires to claim the benefit of a prior-filed application under 35 U.S.C. 119(e), 120, 121, 365(c) or 386(c), the instant application must contain, or be amended to contain, a specific reference to the prior-filed application in compliance with 37 CFR 1.78. If the application was filed before September 16, 2012, the specific reference must be included in the first sentence(s) of the specification following the title or in an application data sheet (ADS) in compliance with pre-AIA 37 CFR 1.76; if the application was filed on or after September 16, 2012, the specific reference must be included in an ADS in compliance with 37 CFR 1.76. For benefit claims under 35 U.S.C. 120, 121, 365(c), or 386(c), the reference must include the relationship (i.e., continuation, divisional, or continuation-in-part) of the applications.
If the instant application is a utility or plant application filed under 35 U.S.C. 111(a), the specific reference must be submitted during the pendency of the application and within the later of four months from the actual filing date of the application or sixteen months from the filing date of the prior application. If the application is a national stage application under 35 U.S.C. 371, the specific reference must be submitted during the pendency of the application and within the later of four months from the date on which the national stage commenced under 35 U.S.C. 371(b) or (f), four months from the date of the initial submission under 35 U.S.C. 371 to enter the national stage, or sixteen months from the filing date of the prior application. See 37 CFR 1.78(a)(4) for benefit claims under 35 U.S.C. 119(e) and 37 CFR 1.78(d)(3) for benefit claims under 35 U.S.C. 120, 121, 365(c), or 386(c). This time period is not extendable and a failure to submit the reference required by 35 U.S.C. 119(e) and/or 120, where applicable, within this time period is considered a waiver of any benefit of such prior application(s) under 35 U.S.C. 119(e), 120, 121, 365(c), and 386(c). A benefit claim filed after the required time period may be accepted if it is accompanied by a grantable petition to accept an unintentionally delayed benefit claim under 35 U.S.C. 119(e) (see 37 CFR 1.78(c)) or under 35 U.S.C. 120, 121, 365(c), or 386(c) (see 37 CFR 1.78(e)). The petition must be accompanied by (1) the reference required by 35 U.S.C. 120 or 119(e) and by 37 CFR 1.78 to the prior application (unless previously submitted), (2) the applicable petition fee under 37 CFR 1.17(m)(1) or (2), and (3) a statement that the entire delay between the date the benefit claim was due under 37 CFR 1.78 and the date the claim was filed was unintentional. The presentation of a benefit claim may result in an additional fee under 37 CFR 1.17(w)(1) or (2) being required, if the earliest filing date for which benefit is claimed under 35 U.S.C. 120, 121, 365(c), or 386(c) and 1.78(d) in the application is more than six years before the actual filing date of the application. The Director may require additional information where there is a question whether the delay was unintentional. The petition should be addressed to: Mail Stop Petition, Commissioner for Patents, P.O. Box 1450, Alexandria, Virginia 22313-1450.
If the reference to the prior application was previously submitted within the time period set forth in 37 CFR 1.78 but was not included in the location in the application required by the rule (e.g., if the reference was submitted in an oath or declaration or the application transmittal letter), and the information concerning the benefit claim was recognized by the Office as shown by its inclusion on the first filing receipt, the petition under 37 CFR 1.78 and the petition fee under 37 CFR 1.17(m)(1) or (2) are not required. Applicant is still required to submit the reference in compliance with 37 CFR 1.78 by filing an ADS in compliance with 37 CFR 1.76 with the reference (or, if the application was filed before September 16, 2012, by filing either an amendment to the first sentence(s) of the specification or an ADS in compliance with pre-AIA 37 CFR 1.76). See MPEP § 211.02.
It is noted that the most recent Filing Receipt, dated October 1, 2021, does not list U.S. Patent Application No. 16/995,829, filed August 18, 2020, as a priority document.
Information Disclosure Statement
The Information Disclosure Statement filed May 29, 2026 has been considered.
Applicants provided an Appendix to the Specification, listing 27 pages of references. In addition, the Specification itself contains additional references. However, the listings of references in the specification are not proper information disclosure statements. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. In addition, although Applicant appears to provide U.S. and International Patent Documents and referenced publications in an Appendix to the Specification, they are still present in the substitute specification filed May 22, 2026. If Applicant wishes to have any of these references considered, they should be in the form of an Information Disclosure Statement. Alternatively, they should be placed between the body of the specification and the claims, rather than after the claims.
Drawings
Applicant omitted Figures 5 and 33. However, Applicants claim priority to U.S. Provisional Patent Application Nos. 63/060,300; 63/076,527; 63/214,612, with the ‘527 application including Figures 5 and 33. If Applicant provides a statement that these three provisional applications are incorporated by reference in their entirety, the ‘527 application can be relied upon to provide reintroduction of Figures 5 and 33 (see below in § Specification).
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.
Specific deficiencies and the required response to this Office Action are as follows:
There are no sequences listed in the Sequence Listing for SEQ ID NOS: 6, 18, 22, 109, 126, 133, and 148. See the Notice to Comply with Sequence Disclosure Requirements.
Specification
While Applicant claims priority to U.S. Provisional Patent Application Nos. 63/060,300; 63/076,527; 63/214,612, there is no statement to incorporate the subject matter of these provisional patent applications into this application by reference. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Although Applicant appears to provide legible Tables, these replacement Tables are present only in the Remarks. The substitute specification filed May 22, 2026 retains the original Tables. The replacement Tables should be inserted into the Specification itself. As a result, Tables 3, 3b, 4, and 5 are still illegible. In addition, Table 5 should not be deleted, even if related to non-elected subject matter, as such a deletion could raise new matter issues going forward.
Regarding the italicization of genus and species names, it appears that Applicant has misunderstood the requirement. Italicization is only required for actual genus/species names in the specification (see, e.g., Mus musculus at page 20, line 12, which should be fully italicized). In addition, while adding “(H. sapiens)” after the word “human” is unnecessary, with regard to the specification, the objection is withdrawn.
The disclosure is objected to because of the following informalities:
At page 82, line 30 and page 165, line 30, “Llentivirus” should be changed to “lentivirus.”
The terms “muscle,” “muscles,” and “must” throughout the specification should not have the “mus” italicized.
Although Applicant appears to provide U.S. and International Patent Document in an Appendix to the Specification, they are still present in the substitute specification filed May 22, 2026. In addition, not all of the listed references are cited in the Information Disclosure Statement filed May 29, 2026.
The use of the terms TALEN® at pages 119-120 and UNIPROT® at page 133 which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 32 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiple dependent claim. See MPEP § 608.01(n). Accordingly, claim 32 has not been further treated on the merits.
Claims 1-5, 7, 9, 11, 14-15, 17, 20, 33-34, and 36-39 are objected to because of the following informalities:
At claim 1, lines 2 and 9, “(Genus Lentivirus)” should be deleted.
At claim 1, line 6, “the” before “transgenes” should be deleted.
At claim 1, lines 14-15 and 16, “(Genus Mus)” should be deleted.
At claim 1, line 15, “(Genus Oryctolagus)” should be deleted.
At claim 1, line 15, “(H. sapiens)” should be deleted.
At claim 1, line 22, “[a]llergens” should be changed to “allergens.” Applicant appears to intend to do this, but the “a” in “allergens” should be underlined, rather than bracketed.
At claim 1, line 20, “or” should be inserted after “ailment,”. Did Applicant intend to insert “or” because “or” is both underlined and struck out.
At claim 2, line 1, “[A]n” should be changed to “An.” Applicant appears to intend to do this, but the “A” in “An” should be underlined, rather than bracketed.
At claim 2, line 3, “(Genus Lentivirus)” should be deleted.
At claim 2, lines 3-4, “(Genus Gammaretrovirus)” should be deleted.
At claim 2, lines 5 and 16, “(H. sapiens)” should be deleted.
At claim 2, line 15, “derived” should be changed to “obtained.”
At claim 2, line 16, “(Genus Mus)” should be deleted.
At claim 2, line 17, “(Genus Inovirus)” should be deleted.
At claim 2, lines 18 and 30, “[t]he” should be changed to “the.” Applicant appears to intend to do this, but the “t” in “the” should be underlined, rather than bracketed.
At claim 2, line 23, “the” before “use” should be deleted.
At claim 2, line 33, the comma after “of” should be deleted.
At claim 3, line 5, “The” should be changed to “the.”
At claim 3, line 9, “[t]he” should be changed to “the.” Applicant appears to intend to do this, but the “t” in “the” should be underlined, rather than bracketed.
At claim 4, line 4, “(Genus Dependoparvovirus)” should be deleted.
At claim 4, line 5, “(Genus Dependoparvovirus)” should be deleted.
At claim 4, line 5, “(Genus Mastadenovirus)” should be deleted.
At claim 4, line 6, “(Genus Mastadenovirus)” should be deleted.
At claim 4, line 9, “(Genus Lentivirus)” should be deleted.
At claim 4, line 10, “or” should be changed to “and.”
At claim 5, lines 4 and 5, “(H. sapiens)” should be deleted.
At claim 5, line 6, “(Genus Dependoparvovirus)” should be deleted.
At claim 7, the parentheses around each sequence identifier should be deleted.
At claim 9, lines 1-2, “(Genus Lentivirus)” should be deleted.
At claim 9, line 3, “(immunoglobulins)” should be deleted.
At claim 9, line 9, “[a]llergens” should be changed to “allergens.” Applicant appears to intend to do this, but the “a” in “allergens” should be underlined, rather than bracketed.
At claim 9, line 19, “(H. sapiens)” should be deleted.
At claim 9, line 22, “derived” should be changed to “obtained.”
At claim 9, line 28, the period after “acids” should be deleted and “Where” should be changed to “where.”
At claim 9, lines 29 and 30, “Chain” should be changed to “chain.”
At claim 11, lines 1-2, “(Genus Lentivirus)” should be deleted.
At claim 11, line 2, “(Genus Gammaretrovirus)” should be deleted.
At claim 11, line 5, “or derived” should be deleted.
At claim 11, line 7, the period after “(Genus Inovirus)” should be deleted.
At claim 11, line 7, “Where” should be changed to “where.”
At claim 11, line 7, “the” should be deleted.
At claim 11, lines 7 and 17, “(Genus Inovirus)” should be deleted.
At claim 11, lines 10, 11, 12, 14, and 15, “(H. sapiens)” should be deleted.
At claim 11, line 27, “Where” should be changed to “where.”
At claim 11, line 28, the period after “cleavage” should be deleted and “Where” should be changed to “where.”
At claim 14, lines 4-5 and 12, “(H. sapiens)” should be deleted.
At claim 15, lines 4 and 12, “(H. sapiens)” should be deleted.
At claim 17, line 4, “(H. sapiens)” should be deleted.
At claim 17, line 7, the period after “(SV40)” should be changed to a comma.
At claim 17, line 11, “The” should be changed to “the.”
At claim 20, lines 4 and 5, “(H. sapiens)” should be deleted.
At claim 20, line 7, the period after “gene” should be deleted and “Where” should be changed to “where.”
At claim 20, line 8, the period after “IRES” should be deleted and “Where” should be changed to “where.”
At claim 33, line 7, “(H. sapiens)” should be deleted.
At claim 33, line 9, “pylori” should be italicized.
At claim 34, line 13, “ex vivo” should be italicized.
At claim 36, line 9, it is believed that “anti” should be changed to “antibody.”
At claim 36, line 13, “in vivo” should be italicized.
At claim 36, line 14, “(see FIGs. 24, and 26)” should be deleted.
At claim 36, line 29, “and,” “or,” or “and/or” should be inserted before “(2).”
At claim 36, line 33, “Must” should be changed to “must.”
At claim 36, line 52, “(in bold font)” should be deleted.
At claim 36, line 60, the period before “(SEQ ID NO: 145 and SEQ ID NO: 146)” should be deleted.
At claim 37, line 5, a comma should be inserted after “lipids.”
At claim 38, line 8, “(H. sapiens)” should be deleted.
At claim 38, line 13, “ex vivo” should be italicized.
At claim 39, line 5, “(H. sapiens)” should be deleted.
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.
Claims 1 and 9 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. This rejection is modified as necessitated by Applicant’s amendments.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
A written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name," of the claimed subject matter sufficient to distinguish it from other materials. Fiers v. Revel, 984 F.2d at 1171,25 USPQA2d, 1601; In re Smyth, 480 F.2d 1376,1383, 178 USPQ 279,284 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is an unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not a sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that, for a generic claim, the genus can be adequately described in the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. This disclosure of only one or a few species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 115; Noelle v. Lederman, 355 F.3d, 1343, 1350, 69 USPO2d 1508, 1514 (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). In addition, it has been well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression, and activities. The instant claims require that the IgG and IgA memory B-cells are derived from the blood of persons previously exposed to, has immune specificity to, or are affected by one or more of viruses, allergies, allergens, fungi, bacterial infection, cancer, an unnatural virus or toxin, microbial infection, any ailment, a target protein or variants including self-antigens. The rejected claims thus comprise a genus of afflictions that provide IgG or IgA memory B-cells being obtained from blood of subjects. 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 a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification states that “[e]pression of dIgA1 and dIgA2 and derivatives of dIgA1 and dIgA2 from mRNA, an episome or genomic DNA via retroviral incorporation of a retroviral vector such as on delivered by a lentivirus or gammaretrovirus is claimed in this instant patent.” See paragraph bridging pages 13 and 14. However, it is impossible for one to extrapolate from the generic recitation of broad classes of afflictions that provide for immune specificity would be useful from which IgG and IgA can be obtained. The prior art does not appear to offset the deficiencies of the instant specification. The prior art teaches that B cells in rejection and tolerance is unpredictable, stating that there is incomplete understanding about the heterogeneity of injury response in organ transplantation (abstract). Further, the disparate mechanistic roles of B cells in organ injury have been increasingly recognized (Zarkhin et al., 24 Seminars in Immunology 86-91 (2012)).Thus, the specification is not sufficient to support the broadly claimed genus of afflictions of subjects from which IgG and IgA B-cells are obtained.
The description of the limited sources of IgG and IgA memory B-cells is not sufficient to support the genus of B-cell sources. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See Vas-Cath at page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is now is claimed." (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of B-cell sources, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation or identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18USPQ2d 1016. Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1 and 9.
Claim 33 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for neutralizing toxic bacteria in mucosa, does not reasonably provide enablement for preventing formation of bacterial colonies or preventing bacterial motility. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This is a new rejection necessitated by Applicant’s amendments.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. They include (1 the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are broadly drawn to a method of preventing formation of bacterial colonies and bacterial motility in mucosa comprising administering a vector encoding a dIgA1 or dIgA2 associated vectors.
The state of the art, the unpredictability of the art, and the relative skill of the ordinary artisan
It is well established in the art that administration of a wide therapeutics are able to treat a cancer, and reduce the symptoms of that disease in a subject. Generally, a variety of antibiotic therapeutics can be prepared and administered to a subject to treat an infection. However, the prevention of formation of bacterial colonies and bacterial motility by administration of a pharmaceutical composition comprising a vector encoding a dIgA1 or dIgA2 is unpredictable. Further, mere administration of such a antibacterial therapeutic at best ameliorates some of the symptoms or progression of an infection, and will not prevent the formation of bacterial colonies or bacterial motility. In addition, the skill of those in the relative art is high, but still, given the state and unpredictability of the art, undue experimentation would be required to determine if growth of bacterial colonies or bacterial motility is prevented, or rather than just treated by administration of the claimed pharmaceutical composition. Prevention of bacterial colony growth or motility cannot be predictably accomplished, much less via the administration of a pharmaceutical composition comprising the claimed vector that comprises a sequence of the dIgA1 or dIgA2.
Amount of experimentation required and the direction or guidance presented
In order to determine how to act, one of ordinary skill in the art would have to practice undue experimentation to determine if bacterial colony growth or motility was prevented by a pharmaceutical composition comprising the claimed vector encoding the dIgA1 or dIgA2. While bacterial infections can be treated, bacterial colony growth or motility thereof cannot necessarily be prevented. Even if an effective therapeutic pharmaceutical composition comprising the claimed dIgA1 or dIgA2 was identified and administered to a subject, the result would be just that: treatment of a bacterial infection in a subject. The ability to administer an composition to a subject having a bacterial infection is not representative of the ability to predictably make and use the invention. In addition, the specification, as filed, fails to provide any particular direction or guidance which resolves the known unpredictability in the art associated with preventing bacterial colony growth or motility in a subject.
Nature of the invention, the presence or absence of working examples, and the breadth of the claims
While the specification does provide potential for the treatment of a bacterial infection, it fails to disclose how to prevent bacterial colony growth and motility, as encompassed by the claims. Because the invention requires that bacterial colony growth and motility be prevented by the administration of a pharmaceutical composition comprising the dIgA1 or dIgA2, rather than treated so as to ameliorate or reduce any disease symptoms, the specification does not provide any disclosure to enable the claims over their full scope.
In view of the lack of the predictability of the art to which the invention pertains, undue experimentation would be required to make and use the claimed invention to prevent bacterial colony growth and motility in a subject, or recurrence thereof, with a reasonable expectation of success. Because the specification does not contain a detailed description of how to make and use the method based on administration of pharmaceutical composition comprising the claimed dIgA1 or dIgA2, according to the invention, and absent working examples that provide evidence that is reasonably predictive of the ability of preventing bacterial colony growth and motility by the administration of a pharmaceutical composition comprising the claimed dIgA1 or dIgA2, the claims are not enabled commensurate in scope with the claimed invention.
Claim 35 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a cancer in a mammalian subject, does not reasonably provide enablement for eliminating allergies, preventing mast cell binding to an allergen, and preventing dendritic cell binding of allergens in a mammalian subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This is a new rejection necessitated by Applicant’s amendments.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. They include (1 the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are broadly drawn to a method of eliminating allergies, preventing mast cell binding to an allergen, and preventing dendritic cell binding of allergens in a mammalian subject comprising administering a vector encoding a dIgA1 or dIgA2.
The state of the art, the unpredictability of the art, and the relative skill of the ordinary artisan
It is well established in the art that administration of a wide therapeutics are able to treat allergies, and reduce the symptoms of allergies in a subject. Generally, a variety of anti-allergy therapeutics can be prepared and administered to a subject to treat allergies. However, the elimination of allergies, preventing mast cell binding to an allergen, and preventing dendritic cell binding of allergens by administration of a pharmaceutical composition comprising a vector encoding a dIgA1 or dIgA2 is unpredictable. Further, mere administration of such an anti-allergy therapeutic at best ameliorates some of the symptoms of the allergy, and will not eliminate allergies, prevent mast cell binding to an allergen, or prevent dendritic cell binding of allergens. In addition, the skill of those in the relative art is high, but still, given the state and unpredictability of the art, undue experimentation would be required to determine if an allergy is eliminated, mast cell binding to an allergen is prevented, and/or dendritic cell binding of allergens is prevented, or rather than just treated by administration of the claimed pharmaceutical composition. Elimination of allergies, prevention of mast cell binding or an allergen, or dendritic cell binding to an allergen cannot be predictably accomplished, much less via the administration of a pharmaceutical composition comprising the claimed vector that comprises a sequence of the dIgA1 or dIgA2.
Amount of experimentation required and the direction or guidance presented
In order to determine how to act, one of ordinary skill in the art would have to practice undue experimentation to determine if an allergy was eliminated, mast cell binding to an allergen is prevented, or dendritic cell binding to an allergen by a pharmaceutical composition comprising the claimed vector encoding the dIgA1 or dIgA2. While allergies can be treated and symptoms reduced, such allergies, mast cell binding to an allergen, and/or dendritic cell binding to an allergen thereof cannot necessarily be eliminated or prevented. Even if an effective therapeutic pharmaceutical composition comprising the claimed dIgA1 or dIgA2 was identified and administered to a subject, the result would be just that: treatment of an allergy in a subject. The ability to administer an composition to a subject having allergies is not representative of the ability to predictably make and use the invention. In addition, the specification, as filed, fails to provide any particular direction or guidance which resolves the known unpredictability in the art associated with eliminating allergies, preventing mast cell binding to allergens, and/or dendritic cell binding to allergens in a subject.
Nature of the invention, the presence or absence of working examples, and the breadth of the claims
While the specification does provide potential for the treatment of allergies, it fails to disclose how to eliminate allergies, prevent mast cell binding to an allergen, and/or prevent dendritic cell binding of allergens, as encompassed by the claims. Because the invention requires that an allergy be eliminated, that mast cell binding to allergens be prevented, and/or dendritic cell binding to allergens by the administration of a pharmaceutical composition comprising the dIgA1 or dIgA2, rather than treated so as to ameliorate or reduce any allergy symptoms, the specification does not provide any disclosure to enable the claims over their full scope.
In view of the lack of the predictability of the art to which the invention pertains, undue experimentation would be required to make and use the claimed invention to eliminate allergies, prevent binding of mast cells to allergens, and/or prevent binding of dendritic cells to allergens in a subject with a reasonable expectation of success. Because the specification does not contain a detailed description of how to make and use the method based on administration of pharmaceutical composition comprising the claimed dIgA1 or dIgA2, according to the invention, and absent working examples that provide evidence that is reasonably predictive of the ability of eliminating allergies, preventing mast cell binding to allergens, and/or preventing dendritic cell binding to allergens by the administration of a pharmaceutical composition comprising the claimed dIgA1 or dIgA2, the claims are not enabled commensurate in scope with the claimed invention.
Claim 38 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a cancer in a mammalian subject, does not reasonably provide enablement for preventing cancer metastasis in a mammalian subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This is a new rejection necessitated by Applicant’s amendments.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. They include (1 the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are broadly drawn to a method of preventing cancer metastasis in a mammalian subject comprising administering a vector encoding a dIgA1 or dIgA2 associated necitumumab allotypes.
The state of the art, the unpredictability of the art, and the relative skill of the ordinary artisan
It is well established in the art that administration of a wide therapeutics are able to treat a cancer, and reduce the symptoms of that disease in a subject. Generally, a variety of cancer therapeutics can be prepared and administered to a subject to treat the cancer. However, the prevention of cancer metastasis by administration of a pharmaceutical composition comprising a vector encoding a dIgA1 or dIgA2 associated necitumumab allotypes is unpredictable. Further, mere administration of such a cancer therapeutic at best ameliorates some of the symptoms or progression of a tumor, and will not prevent the cancer or metastasis of the cancer. In addition, the skill of those in the relative art is high, but still, given the state and unpredictability of the art, undue experimentation would be required to determine if a tumor is prevented, or rather than just treated by administration of the claimed pharmaceutical composition. Prevention of cancer metastasis cannot be predictably accomplished, much less via the administration of a pharmaceutical composition comprising the claimed vector that comprises a sequence of the dIgA1 or dIgA2 associated necitumumab allotypes.
Amount of experimentation required and the direction or guidance presented
In order to determine how to act, one of ordinary skill in the art would have to practice undue experimentation to determine if cancer metastasis was prevented by a pharmaceutical composition comprising the claimed vector encoding the dIgA1 or dIgA2 associated necitumumab allotypes. While cancer can be treated or go into remission, such cancer metastasis thereof cannot necessarily be prevented. Even if an effective therapeutic pharmaceutical composition comprising the claimed dIgA1 or dIgA2 associated necitumumab allotypes was identified and administered to a subject, the result would be just that: treatment of a cancer in a subject. The ability to administer an composition to a subject having cancer is not representative of the ability to predictably make and use the invention. In addition, the specification, as filed, fails to provide any particular direction or guidance which resolves the known unpredictability in the art associated with preventing cancer metastasis in a subject.
Nature of the invention, the presence or absence of working examples, and the breadth of the claims
While the specification does provide potential for the treatment of a cancer, it fails to disclose how to prevent cancer metastasis, as encompassed by the claims. Because the invention requires that a cancer metastasis be prevented by the administration of a pharmaceutical composition comprising the dIgA1 or dIgA2 associated necitumumab allotypes, rather than treated so as to ameliorate or reduce any disease symptoms, the specification does not provide any disclosure to enable the claims over their full scope.
In view of the lack of the predictability of the art to which the invention pertains, undue experimentation would be required to make and use the claimed invention to prevent cancer in a subject, or recurrence thereof, with a reasonable expectation of success. Because the specification does not contain a detailed description of how to make and use the method based on administration of pharmaceutical composition comprising the claimed dIgA1 or dIgA2 associated necitumumab allotypes, according to the invention, and absent working examples that provide evidence that is reasonably predictive of the ability of preventing cancer metastasis by the administration of a pharmaceutical composition comprising the claimed dIgA1 or dIgA2 associated necitumumab allotypes, the claims are not enabled commensurate in scope with the claimed 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.
Claims 1-7, 9, 11, 14-15, 17-18, 20, and 33-39 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. These are new and maintained rejections necessitated by Applicant’s amendments.
Claim 1 recites the limitation " the vectors according to claim 2" in lines 6-7. There is insufficient antecedent basis for this limitation in the claim. Claim 2 recites “an mRNA, viral, non-viral, or retroviral a lentiviral vector or gammaretroviral vector” and it is unclear if claim 1 encompasses all the potential vector or a single vector of one of the claimed vector types.
Claim 1 recites the limitation "the immunoglobulin light chain, heavy chain, and J chain" in lines 9-10. There is insufficient antecedent basis for this limitation in the claim.
Claims 4-7, 9, 14, 17-18, 20, and 33-39 depend from claim 1, and are therefore included in these rejections.
Claim 2 recites the limitation " the vectors" in line 6. There is insufficient antecedent basis for this limitation in the claim. Claim 2 recites “an mRNA, viral, non-viral, or retroviral vector” and it is unclear if the claim encompasses all the potential vector or a single vector of one of the claimed vector types.
Claims 1, 4-7, 9, 11, 14, 17-18, 10, and 33-39 depend from claim 2, and are therefore included in this rejection.
Claim 3 recites the limitation "the two transgenes" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “two” be deleted.
Claim 3 recites the limitation "the subsequent transgene" in lines 7-8. There is insufficient antecedent basis for this limitation in the claim.
Claims 4-7, 9, 14, 17-18, 10, and 35 depend from claim 3, and are therefore included in these rejections.
At claim 5, line 11, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
Claim 6 recites the limitation "the sequence encoding the furin cleavage site" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claim 6 recites the limitation "the consensus sequence" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claim 7 depends from claim 6, and is therefore included in these rejections.
Claim 9 recites the limitation "the cell" in line 13. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the source in” be deleted.
Regarding claim 9, the phrase "for example" (e.g.) at line 25 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 14 recites the limitation "the promoter and intermediate promoter" in line 2. There is insufficient antecedent basis for this limitation in the claim.
At claim 14, lines 6-7, it is not clear what is meant by a similar function to an intermediate promoter. Is there a specific strength the promoter must have in order to have a similar function? Is there a specific intermediate promoter to which the similar promoter must be compared?
Claim 14 recites the limitation "the natural promoter or truncated promoter" in line 11. There is insufficient antecedent basis for this limitation in the claim.
At claim 14, lines 11-12, it is not clear what is meant by the phrase “highly expressed.” Highly expressed is a relative term that is not specified.
At claim 14, lines 13-16, it is unclear if the specific promoters must have the sequences listed. For the purpose of examination, the claim is interpreted as encompassing only the type of promoter, rather than the specific sequence.
Claim 15 recites the limitation "the promoter and intermediate promoter" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For the purpose of examination, the claim is interpreted as encompassing only the type of promoter, rather than the specific sequence.
At claim 15, lines 6-7, it is not clear what is meant by a similar function to an intermediate promoter. Is there a specific strength the promoter must have in order to have a similar function? Is there a specific intermediate promoter to which the similar promoter must be compared?
Claim 15 recites the limitation "the natural promoter or truncated promoter" in lines 10-11. There is insufficient antecedent basis for this limitation in the claim.
At claim 15, lines 11 and 12, it is not clear what is meant by the phrase “highly expressed.” Highly expressed is a relative term that is not specified.
At claim 15, lines 13-16, it is unclear if the specific promoters must have the sequences listed.
Claim 17 recites the limitation "the intermediate promoter" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 recites the limitation "the polyadenylation site" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “site” be changed to “element.”
Claim 18 recites the limitation "the polyclonal expression" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be deleted.
At claim 18, line 3, it is not clear what is meant by the phrase “may consist.” Do the immunoglobulins being expressed result in a mix of immunoglobulins or not?
Claim 20 recites the limitation "the final transgene" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the remaining part of the vector" in lines 9-10. There is insufficient antecedent basis for this limitation in the claim.
Claim 33 recites the limitation "the infected human" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 33 recites the limitation "the Helicobacter pylori adhesin protein HopQ" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 34 recites the limitation "the apical face of the epithelium" in lines 3 and 4. There is insufficient antecedent basis for this limitation in the claim.
At claim 34, lines 6-7 and 7, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
Claim 34 recites the limitation "the antibody" in line 12. There is insufficient antecedent basis for this limitation in the claim. Does this refer to dIGA1, dIgA2, or to some other antibody?
Claim 15 depends from claim 34, and is therefore included in these rejections.
Claim 35 recites the limitation "the vectors" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “vectors” be changed to “vector.”
Claim 35 recites the limitation "the allergen protein" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 35 recites the limitation "the allergen" in lines 8-9. There is insufficient antecedent basis for this limitation in the claim.
At claim 36, line 11, it is unclear if the specific Feek promoter must have the sequence listed. For the purpose of examination, the claim is interpreted as encompassing only the type of promoter, rather than the specific sequence.
Claim 36 recites the limitation "the expression of dIGA1-HGN194" in lines 11-12. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be deleted.
At claim 36, line 16, it is not clear what is meant by the phrase “an appropriately engineered GP120/GP41.” What characteristics are required for a GP120/GP41 to be “appropriately” engineered?
At claim 26, lines 21-22, it is not clear what is meant by the phrase “a benign vector cassette.”
Claim 36 recites the limitation "the vector construct" in lines 24 and 30 . There is insufficient antecedent basis for this limitation in the claim. It is suggested that “construct” be deleted.
At claim 36, line 26, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
At claim 36, lines 26-27, it is not clear what is meant by the phrase “a manner similar to claim 2.” What portion of claim 2 must be adhered to in order to be considered “a manner similar to claim 2’?
Claim 36 recites the limitation "the subsequent transgene" in line 28. There is insufficient antecedent basis for this limitation in the claim.
At claim 36, lines 33-34, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
Claim 36 recites the limitation "the secreted immunoglobulin heavy chain" in line 35. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the nucleotide sequence" in line 35. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the nucleotide sequence" in line 35. There is insufficient antecedent basis for this limitation in the claim.
At claim 36, line 37, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
At claim 36, lines 38-42, it is not clear if the information in the parentheses is intended to be a claim limitation or not. For the purpose of examination, the claim is interpreted as the information in parentheses is not a claim limitation.
Claim 36 recites the limitation "the immunoglobulin heavy chain tailpiece" in lines 40-41. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the single open reading frame" in line 47. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the required sequence in all configurations” in line 50. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the exon splice acceptor site" in line 53. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the remaining sequence" in line 53. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the transmembrane domain" in lines 54-55. There is insufficient antecedent basis for this limitation in the claim.
At claim 36, lines 55-61, it is not clear what the order of the sequences SEQ ID NO: 145 and SEQ ID NO: 146. For the purpose of examination, the claim is interpreted as including a transmembrane domain, but not the specified sequences.
Claim 36 recites the limitation "the transmembrane domain" in lines 54-55. There is insufficient antecedent basis for this limitation in the claim.
Claim 37 recites the limitation "mRNA" in lines 3 and 5. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “vector” be inserted after “mRNA.”
At claim 37, lines 6-7, it is not clear if other cell surface proteins are encompassed by the claim or if only the adhesin SpsA is required.
Claim 38 recites the limitation "the apical face of the epithelium" in lines 2-3 and 4. There is insufficient antecedent basis for this limitation in the claim.
At claim 38, lines 6 and 7, it is not clear if the information in the parentheses is intended to be a claim limitation or not.
Claim 38 recites the limitation "the antibody" in line 12. There is insufficient antecedent basis for this limitation in the claim. Does this refer to dIGA1, dIgA2, or to some other antibody?
Claim 38 recites the limitation "the patient" in line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 39 recites the limitation "the infected human" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 39 recites the limitation "the lumen" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 39 recites the limitation "the Helicobacter pylori adhesin protein HopQ" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
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 (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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-6, 9, 11, 14-15, 17-18, 20, 33-35, 37, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Rawlings et al. (PCT Patent Application Publication No. WO 2019/241721, published December 19, 2019) in view of Zhou et al. (11 Retrovirology 109, 1-11 (2014)), Baliga et al. (U.S. Patent Application Publication No. 2021/0087273, published March 25, 2021 and claiming priority to U.S. Patent Application No. 16/827,100, filed March 23, 2020, now U.S. Patent No. 10,899,835, PCT Patent Application No. PCT/US2019/020374, filed March 1, 2019, and U.S. Provisional Patent Application No. 62/637,186, filed March 1, 2018), and Fang et al. (15(6) Molecular Therapy 1153-1159 (2007)),. This is a new rejection necessitated by Applicant’s amendments.
Regarding claim 1, Rawlings discloses episomal expression, genomic integrated lentiviral vector, or gammaretroviral vector-based expression of mRNA expression of monoclonal or polyclonal antibodies (paragraphs [00296], [00300], and [00449]). Rawlings discloses that the antibodies can be of one or more of isotypes and can be polymeric, including IgA, or class, including IgA1, IgA2, IgG1, IgG2, IgG3, and dlgA1 (paragraphs [00142], [00169], [00192], and [00530]). Rawlings discloses that episome, genomic integrated lentiviral vector, or mRNA encodes for a polypeptide sequence for immunoglobulins light and heavy chains, in which VH and VL domains are expressed, as well as a J-chain (paragraphs [0023 and [00214]). Rawlings discloses that the J chain allows for joining of the pentameric immunoglobulin structures and therefore is forming dimeric IgA1 and IgA2 that is expressed in the same cell (paragraphs [00124] and [00207]). Rawlings discloses that the cell is identified from one or more of CD27+ IgG memory B-cells, CD27+ IgA memory B-cells, any memory B-cell, memory plasma B-cell, plasma B- cells, plasmablasts, cells from any transgenic animal, cells from a mouse or rabbit with a humanized immunized system, or from a mouse other non-human vertebrate antibody converted into a chimeric antibody (paragraphs [00071]-[00072]). Rawlings discloses that the IgG memory B-cells can be derived from the blood of persons or animals who are currently infected with, were previously infected, were previously exposed to, have immune specificity to, or affected by one or more of a virus or a plurality of viruses, a systemic ailment such as allergies, allergens, fungi, bacterial infection, cancerous tumor, an unnatural virus or toxin, a microbial infection, any ailment, a target protein, or variant including self-antigens that comprises or expresses the antigen of interest (paragraphs [00072]-[00073] and [00078]).
Regarding claim 2, Rawlings discloses a B-cell of interest and mRNA, viral, non-viral, or retroviral vectors, including lentiviral vectors, hybrid adenoviral vectors, and herpes simplex viral vectors, and gammaretroviral vectors (paragraphs [00298, 00300]-[00301], and [00345]). Rawlings discloses that these vectors can code for one or more of dimeric immunoglobulin Al (dIgA1). and/or dlgA2 (paragraphs [00169. 00192]). Rawlings discloses that the vector contains the transgenes in any order for an immunoglobulin light chain that may be kappa (IgLκ) or lambda (IgLλ) (paragraph [00192]) as determined from gene sequencing of the B-cell of interest in claim 1 (paragraph [00345]) and J-chain (paragraph [0023]) or an immunoglobulin light chain that may be kappa (IgLκ) or lambda (IgLλ) (paragraph [00192]) as determined from the B-cell and J chain, where the immunoglobulin light and heavy chains encoded for in any nucleic acid vector were expressed by the same B-cell (paragraph [00124]).
Regarding claim 3, Rawlings discloses an mRNA, viral vector, non-viral vector or retroviral vector coding for any one of IgG1, IgG2, IgG3, IgA1, or IgA2, the vector containing in any order of the transgenes for the immunoglobulin heavy chain IgH, the immunoglobulin light chain that may be kappa (lgLκ) or lambda (IgLλ) (paragraphs [00169] and [00192]) as determined from B cell clones, as discussed above (paragraphs [00298, 00300], and [00345]).
Regarding claim 4, Rawlings discloses construction of viral vectors, retroviral vectors, non-viral vectors, or mRNA vectors selected from one or more of the group consisting of an adeno-associated virus (AAV) vector, an AAV vector, an adenovirus viral vector, a self-inactivating replication-incompetent lentivirus retroviral vector, a self-inactivating replication-incompetent gammaretroviral vector, a self-inactivating lentiviral vector, a self-inactivating gammaretroviral vector, a non-viral vector, and an mRNA vector (paragraph [00298]).
Regarding claim 5, Rawlings discloses delivery to host cells or directly to a patient (paragraph [00298] and [00323]).
Regarding claim 9, Rawlings discloses the episomal, genomic integrated lentiviral vector or gammaretroviral vector, or mRNA expression of monoclonal antibody polypeptide sequence or polyclonal antibody polypeptide sequence for VH and VL immunoglobulin light and heavy chains (paragraphs [00298], [00300], and [00449]). Rawlings discloses that IgG and IgA B-cells (paragraph [00124]) are derived from blood of persons or animals who are currently infected with, were previously infected, were previously exposed to, has immune specificity to, or affected by one or more of a virus or a plurality of viruses, a systemic ailment such as allergies, allergens, fungi, bacterial infection, cancerous tumor, an unnatural virus or toxin, any ailment, a target protein, or variant, an immune system protein such as immunoglobulin class E (IgE) or a cytokine that comprises or expresses the antigen of interest (paragraph [[00072]-00073], [00078]). Rawlings discloses that the antibodies can be modified in the following ways: V-regions are coded for as were identified from the source in the cell expressing a potent immunoglobulin or one or more of VL and VH may optionally have one or more of the Complementary Determining Regions (CDR) or Framework regions (FR) modified or replaced with another FR region (paragraphs [00373] and [00376]). Rawlings discloses that one or more of the domains of the immunoglobulin heavy chain constant domains consisting of CH1, hinge, and CH2 are replaced by one or more of natural human derived constant regions to reduce immunogenicity and/or modulate effector functions, engineered constant regions to modulate effector functions, and/or adding a furin cleavage site residue to C-terminal end of the immunoglobulin heavy chain (paragraphs [0010], [00214]-[00215]). Rawlings discloses that CH3 should be derived from IgA1 or IgA2, regardless of whether it is engineered or not and that the immunoglobulin light chain's constant regions (CL) is optionally added or modified by one or more of changing type ( kappa (κ) to lambda (λ)) or lambda (λ) to kappa (κ)), such that the light chain can be a kappa chain or a lambda chain (paragraph [00192]). Rawlings further discloses that additional modifications include adding a furin cleavage site residue on the C-terminal end, modifying the hinge length, modifying the hinge amino acids or amorphous chain amino acids, where the dIgA immunoglobulins use immunoglobulin heavy and light chains identified from a single IgA and through incorporating J-chain into the vector where the J-chain may optionally be modified by adding a furin cleavage site to its C-terminal end (paragraphs [00023] and [00207]).
Regarding claim 11, Rawlings discloses an episomal, genomic integrated lentiviral vector or gammaretroviral vector, or mRNA expression vector (paragraphs [00298, 00300[) of polyclonal or monoclonal antibodies (paragraph [00449]) immunoglobulins) based on one or more of dlgA1 and dlgA2 (paragraphs [00207], [00298], and [00300]). Rawlings discloses the J-chain allows for joining of the pentameric immunoglobulin structures, thereby forming dimeric IgA1 and IgA2 (dlgA1 and dlgA2) (paragraph [00207]). Rawlings discloses that both the VH and VL regions are expressed (heavy chain and light chain) (paragraph [00214]). Rawlings discloses that the antibody binding fragments (Fab) are identified or derived from single chain variable fragments {scFv) or Fab from combinatorial libraries, produced by a Fab expression library (paragraphs [00102] and [00191]). Rawlings discloses that the expression is assessed by phage display technology; where scFv is used to identify VI and VL fragments (paragraph [00102]). Rawlings discloses that the VL and VH polypeptides are joined by a linker polypeptide (paragraphs [00185] and [00493]). Rawlings discloses that the polypeptides are used for the formation in one or more of dlgA1 and dIgA2, with the J-chain allowing for joining of the pentameric immunoglobulin structures thereby forming dimeric IgA1 and IgA2 (paragraph [00207]). Rawlings discloses polymeric immunoglobulin digA1 and/or dIgA2 produced by random recombination and shuffling with optional mutagenesis of human VH and VL regions of scFv from human antibody libraries derived from different human B-cells including, naive B-cells, memory B-cells, and plasma secreting B-cells used to identify potent immunoglobulin VH and VL regions pairs that may be used to recombine the VL with the constant regions of the immunoglobulin light chain and combining the VH regions with any of the constant region of IgA1 and IgA2 (paragraphs [00102], [00191], and [00207]). Rawlings discloses modified hinge variants that may be used to reduce immunogenicity to produce engineered dimeric immunoglobulins of one or more of dlgA1 and dlgA2 from the same vector and as a result of 2A self-processing peptides cleavage/ribosomal skip (paragraphs [00102], [00191], and [00207]).
Regarding claim 18, Rawlings discloses expression of immunoglobulins from vectors, which is interpreted as being polyclonal expression (paragraphs [00294] and [00506]).
Regarding claim 20, Rawlings discloses the use of both 5’ and 3’ untranslated regions (UTRs), which may precede or follow coding regions (paragraph [00300]).
Regarding claims 33-35 and 39,, Rawlings discloses the episomal, genomic integrated lentiviral vector, gammaretroviral vector, or mRNA expression of monoclonal antibody polypeptide sequence or polyclonal antibody (immunoglobulin) polypeptide sequence for VH and VL. immunoglobulin light and heavy chains (paragraphs [00298], [00300], and [00449]). Rawlings discloses previously identified potent immunoglobulins where IgG and IgA B-cells are derived from the blood of persons or animals who are currently infected with or were previously infected with, exposed to or affected by one or more of a virus, a systemic ailment such as but not limited to allergies, allergens, fungi, bacterial infection, cancerous tumors, an unnatural virus or toxin, any ailment, a target protein or variant, or an immune system protein such as immunoglobulin class E (IgE) or a cytokine (paragraphs [00072]-[00073] and 00078]). Rawlings discloses that the immunoglobulins can be modified , with an IgG1, IgG3, IgA1, IgA2, dlgA1 or dlgA2 immunoglobulin identified to be of moderate to high association constant against the protein of interest may be modified by generating the dlgA1 or dlgA2 recombinant isotype of that immunoglobulin by using the dlgA1 or dlgA2 heavy chain constant region to replace the constant region of the parent immunoglobulin (paragraphs [00103], [00193, 00194]). Rawlings discloses that the resulting dlgA1 or dlgA2 antibody where the J chain allows for joining of the pentameric immunoglobulin structures and forming dimeric IgA1 and IgA2 (paragraph [00207]). Rawlings discloses that the antibodies may be modified by engineering the constant domains to modify Fe receptor binding with mutagenesis techniques or with mixes of two constant regions from two isotypes or subclasses that may be modified by replacing one or more of the CH1, hinge or CH2 regions with one or more of one or more of the CH1, hinge, or CH2 regions respectively as a one-to-one correspondence of replacement (paragraph [00215]) or by replacing the Fab or F(ab')2-as identified from the B-cell with the dlgA1 or dlgA2 Fab or F(ab')2 respectively (paragraph [00215]).
Regarding claim 37, Rawlings discloses treating pneumonia where the vector is encapsulated in liposomes or nanoparticles (paragraphs [00272]-[00274], [00322], and [00327]).
Rawlings does not explicitly disclose or suggest dimeric IgA1 or IgA2. Rawlings does not disclose or suggest sequencing the expression antibodies and antibody fragments using sequencing protocols. Rawlings does not disclose that the vector comprises, in the 5' to 3' direction, a promoter operably linked to the two transgenes expressed as a single open reading frame where each transgene is separated from the subsequent transgene in the 5' to 3' direction by a furin cleavage site, a sequence encoding a 2A self-processing cleavage site or that the vector comprises in the 5' to 3' direction the use of separate promoters and polyadenylation elements for each transgene.
Zhou discloses that IgA molecules are important components of mucosal fluids (abstract). Zhou discloses that dimeric IgA1 and IgA2 (dIgA1 and dIgA2), as well as IgG1 versions are protective against HIV (abstract and Figure 1). Although Zhou discloses that dIgA1 is more protective than dIgA2, Zhou discloses that both do show protection against infection in vivo (abstract and Figures 1 and 3).
Baliga discloses a heavy chain, a light chain, and a J-chain construct, which includes two or more nucleic acid sequences encoding two or more or all three polypeptide subunits (paragraph [0152]). Baliga discloses that the vectors provide for increased serum half-life of the antibody.
Regarding claim 3, Fang discloses opportunities for delivery of therapeutic monoclonal antibodies in the clinic (abstract). Fang discloses a vector comprising in the 5' to 3' direction a promoter operably linked to the two transgenes expressed as a single open reading frame where each transgene is separated from the subsequent transgene in the 5' to 3' direction by a furin cleavage site (page 1153, column 1 and 2, first paragraph of "Introduction" section). Fang discloses the expression of full-length two-chain antibodies from a single open reading frame (ORF) by linking the heavy and light antibody chains with a 2A self-processing sequence and a furin cleavage site, a sequence encoding a 2A self-processing cleavage site; or the vector comprising in the 5' to 3' direction the use of separate promoters and polyadenylation elements for each transgene with the optional use of a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) to precede one or more polyadenylation elements (page 1153, column 1 and 2, first paragraph of "Introduction" section).
Regarding claim 6, Fang discloses the furin cleavage sites RAKR, RKRR, RRRR, and RRKR, each of which is encompassed by instant SEQ ID NO: 12 (page 1157, paragraph bridging columns 1 and 2).
Regarding claims 14-15 and 17, Fang discloses use of a cytomegalovirus-based (CAG) promoter (page 1153, column 2, first full paragraph and page 1154, paragraph bridging columns 1 and 2 and Figure 1). Fang also discloses use of an SV40 promoter (Figure 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector construct as disclosed by Rawlings and Zhou to incorporate the ORF, furin cleavage site, and cytomegalovirus CAG or SV40 promoters, and 2A self-processing cleavage site, as disclosed by Fang and Baliga, to provide the benefit of regulated high-level expression of native full-length mAbs in vivo and to offer a new opportunity for delivery of therapeutic mAbs in the clinic.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Rawlings’ disclosure of polymeric IgG antibodies could be extrapolated to Zhou’s disclosure of polymeric IgA molecules, including Zhou’s dIgA1 and dIgA2. Because polymeric antibodies are known, as disclosed by Rawlings and Zhou, one of ordinary skill in the art would have had a reasonable expectation of success in producing dIgA1 and/or dIgA2 according to the processes of Rawlings. One of ordinary skill in the art would have been motivated to do so due to the protective properties against HIV infection of Zhou’s dIgA1 and/or dIgA2.
It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used sequencing to identify Rawlings’ and Zhou’s dimeric IgA1 and IgA2 VH or VL of the scFv because this is a well-known molecular biology technique that is employed to determine the identity of expressed sequences, including antibody and immunoglobulin sequences. Because the technique is so well-known, one of ordinary skill in the art would have been motivated to identify the immunoglobulin fragments in an accurate and reproducible manner.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector construct as disclosed by Rawlings, Zhou, Baliga, and Fang to incorporate the ORF comprising dimerized antibodies of Baliga, as Rawlings, Zhou, and Fang taken together disclose IgA1 and IgA2, digA1 or digA2 (dimerized versions), to provide tile benefit of regulated high-level expression of native full-length mAbs in vivo and which provides a new opportunity for delivery of therapeutic mAbs in the clinic, as disclosed by Fang.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector construct as disclosed by Rawlings, Zhou, Baliga, and Fang to incorporate a single construct with the heavy, light, and J-chain, as disclosed by Baliga, to provide the benefit of increased serum half-life upon the antibody.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Rawlings in view of Zhou, Baliga, and Fang et al. (15(6) Molecular Therapy 1153-1159 (2007)), as applied to claims 1-6, 9, 11, 14-15, 17-18, 20, 33-35, 37, and 39 above, and further in view of Knaut et al. (U.S. Patent Application Publication No. 2015/0065376, published March 5, 2015). This is a new rejection necessitated by Applicant’s amendments.
Rawlings, Zhou, Baliga, and Fang disclose and suggest vectors and methods for preparing dIgA1 and dIgA2, as discussed above.
Rawlings, Zhou, Baliga, and Fang do not disclose or suggest that the a 2A self-processing cleavage site having the sequence of SEQ ID NO: 15.
Knaut discloses expression constructs that can include an internal ribosome entry site (IRES) (abstract). Knaut discloses that the expression constructs can also include a 2A self-processing cleavage site (paragraphs [0008]-[0009]). Knaut discloses the 2A self-processing cleavage site can have a that is identical to instant sequence of SEQ ID NO: 15 (Appendix I SEQ ID NO: 15) (SEQ ID NO: 50, paragraph [0038] and Table 3).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Knaut’s 2A self-processing cleavage site for the 2A self-processing cleavage site disclosed by Rawlings, Zhou, Baliga, and Fang in the expression vector and methods disclosed and suggested by Rawlings, Zhou, Baliga, and Fang because both Knaut’s 2A self-processing cleavage site and Fang’s 2A self-processing cleavage site are well-known. As such, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting Knaut’s well-known 2A self-processing cleavage site in place of Fang’s well-known 2A self-processing cleavage site.
Response to Amendments and Arguments
Regarding the missing Figures 5 and 33, it is noted that Applicant did not address this issue. Therefore, the objection to the drawings is maintained.
Regarding the objections to the claims, Applicants amendments have obviated several of these rejections. However, some objections are maintained, as discussed above, and new objections necessitated by Applicant’s amendments are set forth above. It is also noted that deletions should be struck out or double bracketed. Insertions should be underlined.
Regarding the written description rejection under 35 U.S.C. § 112(a)/first paragraph, Applicant appears to be discussing this rejection under the heading of 102(a)(2), which is not the correct statute for this rejection. However, Applicant’s arguments have been fully considered, and are not deemed to be persuasive.
Applicant asserts that antibody discovery is well characterized, and that there are well established methods that are universally known in the field of antibody and drug discovery. Applicant further asserts that the purpose of the instantly claimed invention is a platform and a defined usage of the platform.
However, Applicant appears to misunderstand the rejection, as set forth previously and above. The rejection is not based on antibody or drug discovery, which, as Applicant points out is well characterized. The rejection is based on the claims requirement that the IgG and IgA memory B-cells are derived from the blood of persons previously exposed to, has immune specificity to, or are affected by one or more of viruses, allergies, allergens, fungi, bacterial infection, cancer, an unnatural virus or toxin, microbial infection, any ailment, a target protein or variants including self-antigens. As noted above, 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 a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification does not include working examples relating to the vast and varying diseases, disorders, and conditions that are recited in the claims. The rejection is not directed to the production of antibody or drug discovery, nor the antibodies produced. The rejection is solely directed to the vast variety of diseases, disorders, conditions, target proteins, as exemplified in the claims as “any ailment.” Because the claims are directed to and encompass an enormous number potential diseases, disorders, ailments, proteins, bacterial and viral infections, allergies, cancer, and toxins, the specification is not sufficient to provide written description over the entire scope of the claim. Therefore, this rejection is maintained.
In addition, new scope of enablement rejections of claims 33, 35, and 38, necessitated by Applicant’s amendments, are set forth above, and related to the prevention and elimination of these diseases, disorders, and conditions.
Regarding the rejections under 35 U.S.C. § 112(b)/second paragraph, Applicants amendments have obviated several of these rejections. However, some rejections are maintained, as discussed above, and new rejections necessitated by Applicant’s amendments are set forth above.
Regarding the rejections under 35 U.S.C. § 102(a)(2), Applicant’s arguments have been fully considered, and are deemed to be persuasive. Therefore, this rejection is withdrawn. However, a new rejection under 35 U.S.C. § 103 is set forth above.
Insofar as Applicant’s arguments are applicable to the rejections set forth above, Applicant asserts that Rawlings describes the ends but not the means to achieve particular outcomes, and are goals and objectives not technologies to achieve those goals and objectives.
To begin, it is noted that the rejection (necessitated by Applicant’s amendments) is now under 35 U.S.C. § 103. And the rejection is based on Rawlings in view of Zhou, Baliga, and Fang. It is noted that Rawlings does disclose polymeric antibodies, including polymeric IgG antibodies, as discussed above. When taken with newly cited Zhou the combination of Rawlings, Zhou, Baliga, and Fang is deemed to recite the same limitations as those listed in the instant claims. Despite Applicant’s assertion that there are numerous and extensive inaccuracies regarding the Rawlings reference, Rawlings in view of Zhou, Baliga, and Fang clearly discloses and suggests the same vectors and expression systems claimed by Applicant. Applicant asserts that Rawlings does not disclose methods for producing antibodies or vector schematics in any drawings and uses “well known techniques” to express antibody light and heavy chains from two separate vectors. Applicant’s assertion that such techniques are well known in the art for more than three decades indicates that the disclosure of Rawlings is on point with regard the production of antibodies, including polymeric antibodies, to the instant claims. Further, newly cited Zhou discloses dIgA1 and dIgA2. Thus, the combination with Rawlings, Zhou, Baliga, and Fang are deemed to render the instant invention obvious.
While Applicant is correct that Rawlings does not disclose furin cleavage sites or 2A self-processing cleavage sites, these limitations are provided by Fang and Knaut, as described above. And, as it appears that Applicant is attacking the references individually, it is noted that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicants make similar arguments regarding the previous rejections under 35 U.S.C. § 103. And it is noted that collectively, taking all details into account, one of ordinary skill in the art having Rawlings in combination with Zhou, Baliga, and Fang (Knaut) would be led directly to the claimed invention. Applicant’s citation of art not applied to the instant claims is not relevant to the rejections. Nor is Applicant’s assertion that the references “represent nothing short of a combinatorial nightmare.” Applicant has provided no objective factually supported evidence that the combination(s) of cited prior art references would not render the instant invention obvious. Rather, Applicants have provided only arguments of counsel, and arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135,139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
Regarding the secondary cited prior art references, Applicant’s argument that Baliga mirrors a technical approach that is “not safe for in [sic] human use” is not relevant. Baliga is cited for the ORF comprising dimerized antibodies, not for the method used to produce the antibodies. Fang is cited for the furin cleavage site, the 2A self-processing cleavage site, and the promoters used. Newly cited Knaut is cited for the sequence of the 2A self-processing cleavage site.
Regarding Applicant’s assertion of impermissible hindsight, it is noted "[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
Regarding Applicant’s assertion of secondary considerations, including long-felt and unmet need, it is noted that, while one single reference does not disclose the instantly claimed invention, the combination of references are deemed to render the instant invention obvious. Each portion of the claimed invention is taught by the combination of Rawlings, Zhou, Baliga, and Fang (and supplemented by Knaut). Regarding Applicant’s discussion of the patents and protocols of Genentech, is again, not relevant to the instant application. Regardless of Genentech’s publications, patents, and products, the instant invention is deemed to render the instantly claimed invention obvious. Taken together and as a whole, Rawlings, Zhou, Baliga, and Fang, with or without Knaut clearly disclose and suggest the instantly claimed invention.
For all these reasons, and those listed above, claims 1-7, 9, 11, 14-15, 17-18, 20, 33-35, 37, and 39 are deemed to render the instant invention obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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