Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of Group I and species in the reply filed on August 27, 2025 is acknowledged.
Claims 1-7, 9-12 are pending. Claim 8, 13-18 are canceled. Claims 1-7, 9-12 are examined.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-7, 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,479,791 in view of Grahames et al. (US 2009/0305321). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1-15 of U.S. Patent No. 11,479,791 does not teach the mammalian host cell of claims 1-7, 9-12 of this application.
Grahames teach the expression of GPCR nucleci acid in host cells including mammalian cells (para 323).
It would have been obvious to one of ordinary skill in the art at the time of the filing to express the vectors of the Grahames in the mammalian host cells. One of ordinary skill in the art would have been motivated to express the mammalian GPCR in the mammalian host cells to study structure in a protein expressed in mammalian cell environment. It is obvious to combine prior art elements according to known methods to yield predictable results.
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 23-34, 36-39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims encompass the method comprising mammalian host cells which express two-fold higher which is not disclosed in the specification. However, the specification does not disclose the method of mammalian host cell which express at least two-fold higher. The specification discloses the specific hCXCR4 and nanobody which are expressed in the mammalian host cell (page 49). The Figure 10 shows expression on a gel but does not teach expression which is at least two-fold higher. Thus, applicant was not in possession of the broad genus of mammalian host cell which expresses two-fold higher as claimed.
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d. Additionally, “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.” Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed. Cir. 2004).
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. The disclosure of only one 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 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (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."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
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 page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what 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 polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. 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, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v.Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the hCXCR4 and nanobody which bind the receptor.
Therefore, claims do not the full breadth of the written description provision of 35 U.S.C. § 112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-7, 9-12 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Rasmussen et al. (Nature, 2011), Steyaert et al.(Current Opinion of Structure Biol., 2011), Callewaert et al. (US 2011/0191913) and Grahames (US 2009/0305321).
Rasmussen et al. teach method of expression host cells, Sf9, comprising beta-adrenergic receptor 2 (B2AR). Rasmussen disclose expression host cells comprising nanobody which bind B2AR. Rasmussen teach the stabilization of nanobody with beta-adrenergic receptor 2 which bind ligand. Rasmussen teach the cell culture and membrane preparation of the host cell. Rasmussen does not teach the host cell comprising both nucleic acids encoding membrane receptor protein and the immunoglobulin single variable domain.
Steyaert et al. teach the stabilization of nanobody with beta-adrenergic receptor 2 is well known to one of skill in the art.
Callewaert et al. disclose pichia yeast host cell for expression of membrane protein including G-protein coupled receptors and fusion proteins using vectors (paragraph 13, 63, 77, 88, 103, 115, 122, 129-134, 138, 142-147, 151, 153, 155, 158-159, 161, 168, 188-192).
Wagner et al. teach for the overexpression of membrane protein such as rhodopsin (a G-protein coupled receptor), the generic intergral membrane chaperones which support the folding of overexpressed protein (page 367, first column, second paragraph).
Grahames teach the expression of GPCR nucleci acid in host cells including mammalian cells (para 323).
It would have been obvious to one of ordinary skill in the art at the time of the invention to use the method of screening compound by expressing the nanobody and B2AR of Rasmussen and Steyaert to incorporate the mammalian host cell expression system of Grahames. One of ordinary skill would be motivated by the ability to study structure of the B2AR with enhanced nanobody stability , structure and the glycosylation effect provided by the mammalian host cell expression system to closer study the pharmaceutical effect on mammalian system. It is obvious to combine prior art elements according to known methods to yield predictable results. The stability of nanobody and B2AR as well as all host expression system including mammalian was well known to one of ordinary skill in the art. The claim limitation “wherein the expression level of the membrane protein is increased as compared to a host cell not comprising the second exogenous polynucleotide” encompass protein stability provided by the nanobody. The motivation is provided by teaching of Wagner where stability of folding of membrane proteins by chaperones increase the overexpression of membrane proteins and the nanobody provides the stability of the B2AR membrane protein which would expect to stabilize the protein folding and support the overexpressed B2AR.
The product by process limitation is met because the detection method of immunoglobulin single variable domain does not exclude nanobody of Rasmussen because the nanobody binds the the B2AR. The method of detecting an increase amount process limitation does not exclude the mammalian expressing B2AR and nanobody. The stability of the B2AR and nanobody provides increased overexpression by two-fold in all host cells and especially in a mammalian host cell with a mammalian protein.
No claims are allowed.
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 MICHAEL D PAK whose telephone number is (571)272-0879. The examiner can normally be reached on flexible.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL D PAK/Primary Examiner, Art Unit 1674