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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 18 November 2025 has been entered.
Election/Restrictions
Claims 21-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 27 April2023.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Claim Rejections - 35 USC § 112
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-01.2024]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
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During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B [R-01-2024], which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10-2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim)
Holding and Rationale
Claims 1-14, 16-17, and 19-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite with respect to the type(s) of IgG antibodies and the organism9s) that produce same, that are encompassed by the claim. In support of this position attention is directed to US 2011/0145937 A1 (MacDonald et al.), which teaches at paragraph [0046]:
[0046] In one embodiment, the mouse expresses four IgGs that are: a modified IgG1 and a wild-type IgG3, IgG2a, and IgG2b. In another embodiment, the mouse expresses no more than two IgGs that are: a modified IgG1 and a wild-type IgG3. (Emphasis added)
Attention is also directed to US 2019/0083665 A1 (Garcia-Martinez et al.), which teach in paragraph [0294]:
It is further contemplated that the human constant regions of chimeric antibodies of the invention may be selected from IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, IgG7, IgG8, IgG9, IgG10, IgG11, IgG12, IgG13, IgG14, IgG15, IgG16, IgG17, IgG18 or IgG19 constant regions. (Emphasis added)
It is also unclear as to just which organism(s) is/are used to produce the “IgG antibody”. In support of this position attention to US 6,300,093 B1 (Kindsvogel et al.), which teaches at column 22, last paragraph:
Antibodies of the present invention may be produced by immunizing an animal, a wide variety of warm-blooded animals such as horses, cows, goats, sheep, dogs, chickens, rabbits, mice, and rats can be used, with a recombinant or synthetic islet cell antigen polypeptide or a selected portion thereof (e.g., a peptide).
In addition to the type(s) of IgG antibody, it is also unclear if the antibody is chimeric and if so, it is unclear if it comprises human sequences.
Claim Rejections - 35 USC § 112, Enablement
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.
Standard for Enablement
It is well settled that in order to satisfy the enablement requirement, “the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 [42 USPQ2d 1001] (Fed. Cir. 1997). (Emphasis added) As set forth in the unanimous decision of the US Supreme Court in Amgen Inc, Petitioners, et al. v. Sanofi, et al. (598 US___ (May, 2023)):
Our decisions in Morse, Incandescent Lamp, and Holland Furniture reinforce the simple statutory command. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable.
For purposes of examination, the aspect of just what constitutes the “full scope” of the claims is that which is consistent with the broadest reasonable interpretation. See MPEP 904.01 and In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is further noted that “routine experimentation is ‘not without bounds.’” Wyeth v. Abbott Laboratories 107 USPQ2d 1273, 1275, 1276 (Fed. Cir. June 2013), citing Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013), and that what constitutes "undue experimentation" can be evaluated from the perspective of the amount of time required to enable the full scope of the invention. In support of this position, attention is directed to Cephalon at 1823, citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 218 USPQ 961 (Fed. Cir. 1983), that work that would require 18 months to 2 years so to enable the full scope of an invention, even if routine, would constitute undue experimentation. As stated therein:
Permissible experimentation is, nevertheless, not without bounds. This court has held that experimentation was unreasonable, for example, where it was found that eighteen months to two years’ work was required to practice the patented invention. See, e.g., White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] Fed. Cir.1983). (Emphasis added)
Holding and Rationale
Claims 1-14, 16, 17, 19, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1 and 2 are the only independent claims pending and under consideration.
Claim 1 is deemed to be representative and, for convenience, is reproduced below.
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33. As evidenced above, the claimed method requires the use of “a monoclonal IgG antibody”. The claims are not limited to the subtype and source of the monoclonal IgG antibody.
US 2011/0145937 A1 (MacDonald et al.), teaches at paragraph [0046]:
[0046] In one embodiment, the mouse expresses four IgGs that are: a modified IgG1 and a wild-type IgG3, IgG2a, and IgG2b. In another embodiment, the mouse expresses no more than two IgGs that are: a modified IgG1 and a wild-type IgG3. (Emphasis added)
Attention is also directed to US 2019/0083665 A1 (Garcia-Martinez et al.), which teach in paragraph [0294]:
It is further contemplated that the human constant regions of chimeric antibodies of the invention may be selected from IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, IgG7, IgG8, IgG9, IgG10, IgG11, IgG12, IgG13, IgG14, IgG15, IgG16, IgG17, IgG18 or IgG19 constant regions. (Emphasis added)
As evidenced above, there are some 20 subtypes of IgE antibodies.
PrecisionAntobody.com (accessed 04/16/2014), teaches:
Our antibody team strives to deliver successful projects to our customers in record time—40 to 60 days for monoclonal projects.
As evidenced above, there are some 20 different subtypes of IgG antibodies, and that antibodies can be produced in some 17 different animals. The claim specified the following 3 targets: “the surface cellular target comprises CD45, and wherein plurality of secreted factors comprises IL-2 and/or TNF-α”. While the claim has been amended so to limit the surface cellular target and secreted to 3 targets, the subtype of monoclonal antibody IgG is not limited. Given such, the claimed methtod has been construed as encompassing all 20 subtypes of IgG antibodies and that the initial immunization of an animal includes all 17 different animals. If monoclonal antibodies can be produced in 40 days, it would take on the order of 40 x 3 x 20 x 17, or 40,800 days or 111.78 years to produce just 1 monoclonal antibody of each IgG subtype in each animal. Such time and effort clearly constitutes an unreasonable amount of effort needed to enable the claimed invention.
In support of this position, attention is again directed to Cephalon at 1823, citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 218 USPQ 961 (Fed. Cir. 1983), that work that would require 18 months to 2 years so to enable the full scope of an invention, even if routine, would constitute undue experimentation. As stated therein:
Permissible experimentation is, nevertheless, not without bounds. This court has held that experimentation was unreasonable, for example, where it was found that eighteen months to two years’ work was required to practice the patented invention. See, e.g., White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] Fed. Cir.1983). (Emphasis added)
As set forth in the unanimous U.S. Supreme Court decision in Amgen Inc., et al. v. Sanofi et al. 598 U.S. ___ (2023):
Our decisions in Morse, Incandescent Lamp, and Holland Furniture reinforce the simple
statutory command. If a patent claims an entire class of processes, machines,
manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405, 419 (1908) (“[T]he claims measure the invention.”). (Emphasis added)
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To be fair, Amgen does not dispute this much. It freely admits that it seeks to claim for
itself an entire universe of antibodies. Still, it says, its broad claims are enabled because scientists can make and use every undisclosed but functional antibody if they simply follow the company’s “roadmap” or its proposal for “conservative substitution.” We cannot agree. These two approaches amount to little more than two research assignments… Whether methods like a “roadmap” or “conservative substitution” might suffice to enable other claims in other patents—perhaps because, as this Court suggested in Incandescent Lamp, the inventor identifies a quality common to every functional embodiment, supra, at 13—they do not here. They leave a scientist about where Sawyer and Man left Edison: forced to engage in “painstaking experimentation” to see what works. 159 U. S., at 475. That is not enablement. More nearly, it is “a hunting license.” Brenner v. Manson, 383 U. S. 519, 536 (1966). (Emphasis added)
Claims 3-14, 16, 17, 19 and 20, which depend from claim 1, fail to overcome the above-identified issues and are similarly rejected.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-14, 16, 17, 19, and 20 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.
Response to argument
At pages 9-15 of the response of 18 November 2025 applicant’s representative traverses the prior rejection of claims under 35 USC 112 for not satisfying the enablement rejection. Attention is directed to the amendment to independent claims 1 and 2 which now recite the limitation that the monoclonal antibody is an IgG antibody.
This traversal has been considered and has not been found persuasive. As noted above, there are some 20 subtypes of the IgG antibody. The claims do not specify which subtype(s). Given such, the claimed method has been construed as encompassing all 20 subtypes, and that such would be produced in all 17 different animals. To do such would take on the order of 40,800 days or 111.78 years. Such an amount of time and effort clearly constitutes undue experimentation. Given such, and in the absence of convincing evidence to the contrary, claims 1-14, 16, 17, 19, and 20 remain 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.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-14, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,392,771 B2 (Song et al.) in view of applicant’s admissions and US 2008/0161365 A1 (Booth et al.).
Claims 1-18 of Song et al., are directed to “a method for measuring the number of copies of a secreted factor secreted by one or more single cells”
Claims 1 and 7 of Song et al., are reproduced below.
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Admissions as Prior Art.
Attention is directed to MPEP 2129 Admissions as Prior Art [R-07.2022], which states in part:
I. ADMISSIONS BY APPLICANT CONSTITUTE PRIOR ART
A statement by an applicant in the specification or made during prosecution identifying the work of another as "prior art" is an admission which can be relied upon for both anticipation and obviousness determinations, regardless of whether the admitted prior art would otherwise qualify as prior art under the statutory categories of 35 U.S.C. 102. Riverwood Int’l Corp. v. R.A. Jones & Co., 324 F.3d 1346, 1354, 66 USPQ2d 1331, 1337 (Fed. Cir. 2003); Constant v. Advanced Micro-Devices Inc., 848 F.2d 1560, 1570, 7 USPQ2d 1057, 1063 (Fed. Cir. 1988). Where the admitted prior art anticipates the claim but does not qualify as prior art under any of the paragraphs of 35 U.S.C. 102, the claim may be rejected as being anticipated by the admitted prior art without citing to 35 U.S.C. 102.
Attention is also directed to Ex parte Shirley, (BPAI, 2009) Appeal No. 2009002352, which, at pages 21 and 26, states:
The Specification’s omission of the term “prior art” and inclusion of the prior-art disclaimer may initially appear to indicate that Appellants do not consider the single-step soft bake process to constitute prior art. To place these latter, contraindicative factors into the proper context though, we note that patent-application drafters regularly endeavor to avoid the indiscriminate or imprudent use of the descriptive label, “prior art.” See Riverwood Intern. Corp. v. R.A. Jones & Co., Inc., 324 F.3d 1346, 1354 (Fed. Cir. 2003) (citing In re Fout, 675 F.2d 297, 300 (CCPA 1982)) for the proposition that “section 102 is not the only source of … prior art. Valid prior art may be created by the admissions of the parties”); In re Nomiya, 509 F.2d 566, 571 (CCPA 1975) (holding that an Applicant’s labeling of certain figures as “prior art,” ipsissimis verbis, constituted an admission that the pictured subject matter was prior art relative to Applicant’s invention); MPEP § 21294 (instructing that “the examiner must determine whether the subject matter identified as ‘prior art’ is applicant’s own work, or the work of another. In the absence of another credible explanation, examiners should treat such subject matter as the work of another”).
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The Specification’s omission of the term “prior art” and inclusion of the boilerplate prior-art disclaimer do not change our conclusion. In view of the record as a whole, these factors are ineffective in shielding Appellants from having their prior-art admissions treated as such.
The claims of the subject application are drawn to “a method for measuring the number of copies of a secreted factor secreted by cells”. The method uses “bispecific probes” which comprise an anchor probe and a capture probe “wherein the anchor probe is capable of specifically binding to the surface cellular target”. The method uses oligonucleotide barcodes.
As seen in claim 3, the plurality of cells are partitioned to where they are rendered single cells. As seen in claim 4, “the plurality of oligonucleotide barcodes are associated with a solid support”. As seen at paragraph [0140] of the disclosure, the solid support can include synthetic particles.
The synthetic particles can be beads. The beads can be silica gel beads, controlled pore glass beads, magnetic beads, Dynabeads, Sephadex/Sepharose beads, cellulose beads, polystyrene beads, or any combination thereof.
As seen in claim 1, the secreted factor can be “IL2 and/or TNF-a” and the “surface cellular target comprises CD45”.
As evidenced above, the patented claimed method is to “a method for measuring the number of copies of a secreted factor secreted by one or more single cells”. As seen in dependent claim 7, “the secreted actor-binding reagents and the capture probe comprise an antibody”; however, the claims in Song et al., have not been found to specify the type of antibody, which, as seen in independent claims 1 and 2 of the instant application, specify that it is “a monoclonal IgG antibody”.
Song et al., in method claims 1, 3, and 8-10, utilizes an “oligonucleotide barcode”. Such is deemed to be analogous to the oligonucleotide barcode recited in claims 1-6 of the instant application.
Booth et al., in paragraph [0139], teach using a monoclonal IgG antibody that binds to TNF-alpha (TNF-α). As stated therein:
[0139] A compound of the present invention may be combined with at least one of the various existing therapeutic agents that are known to treat the same diseases as those disclosed above. For the treatment of rheumatoid arthritis, a compound of the present invention may be preferably combined with at least one therapeutic biologic agent such as CP-870, etanercept, which is a tumor necrosis factor alpha ("TNF-alpha") receptor immunoglobulin molecule, infliximab, which is an anti-TNF-alpha chimeric IgG 1K monoclonal antibody, or adalimumab, which is a human monoclonal anti-TNF-alpha antibody. (Emphasis added)
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art at the time of the invention to have modified the method of Song et al., where the antibody is none other than a monoclonal antibody that is specific for the same antigen- TNF-alpha (TNF-α). By using a monoclonal antibody to bind to the target one is removing a potential variable to the assay.
In view of the above presentation and in the absence of convincing evidence to the contrary, claims 1-14, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,392,771 B2 (Song et al.) in view of US 2008/0161365 A1 (Booth et al.).
Claims 1-14, 16, 17, 19 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,467,157 (Fan et al.; Fan III) in view of WO 2014/031997 A1 (Fan I) and WO 2018/058073 A2 (Fan II).
The '157 patent (Fan III) describes a composition and kit comprising a plurality of oligonucleotide associated antibodies comprising an antibody associated with an antibody
specific oligonucleotide, wherein the antibody comprises a target binding sequence, a unique
identifier sequence, and a universal primer sequence, wherein the antibody can bind to at least
one protein target (see claims 1- 29). The oligonucleotide can comprise a target sequence and a
molecular label sequence (see e.g. claim 1). The antibody specific oligonucleotides can comprise
at least 10 of the oligonucleotides associated antibodies which each comprise a different
molecular label sequence (see e.g. claims 10). The composition can bind an intracellular protein,
a B-cell receptor, a T-cell receptor, or other proteins (see e.g. claim 16). The composition can
also bind CD45 (claim 19). Fan III, at column 68, second paragraph, teaches that the antibodies
can be monoclonal. The '157 patent does not describe binding to a secreted factor, immobilized
antibodies or oligonucleotides, or method steps to use the composition or kit.
Fan I describes a method of multiplex detection of a plurality of compounds from a single
cell, comprising applying single cells into microwells, providing an immobilized capture agent,
which can bind to one of a plurality of compounds, contacting the microwell with the capture
agent, binding compounds to the capture agent, removing the capture agent from the microwell,
contacting the microwell with a plurality of labeled secondary capture agents to bind and form an
immobilized capture agent-compound complex, wherein the presence of the compound can be
detected (see e.g. claim 17). The microwell can comprise a cell (see e.g. claim 20). The compounds can be selected from protein, receptors, hormones, growth factors, and other
compounds (see e.g. claim 22). The compounds can be secreted from the cell (see e.g. claim 23).
The capture agent can be an antibody (see e.g. claim 25). There can be more than one capture
agent, which can have different detectable labels (see e.g. claim 25). The capture agent can
detect at least 10 different compounds (see e.g. claim 30). The cell can be a cancer cell (see e.g.
claims 42-44), or immune cells (see c.g. claim 45). The reference contemplates using two
different epitopes on the target protein in order to provide signal in a sandwich technique (see
e.g. pages 81-82).
Fan I, at page 40, third paragraph, teaches that the antibodies used in the array can be monoclonal. Such is deemed to fairly suggest limitations of independent cla3ims 1 and 2 of the '058 application.
Fan I, at page 50, second paragraph, teach "The device and method of the invention may
be used to determine the presence and/or quantity of any compound." (Emphasis added) Listed
in this paragraph are TNF-α and IL-2.
Fan I does not describe the use of barcoding to detect and measure the captured proteins, simultaneously measuring nucleic acid and protein targets, the attachment of the binding agent or barcodes to solid supports, or use of two different molecular labels to quantitate bound targets. Fan also does not describe bead size.
Fan II teaches measurement of protein expression using reagents with barcoded oligonucleotide sequences (see e.g. abstract, claim 28). The reference teaches a protein binding reagent conjugated with an oligonucleotide, which comprises a unique identifier for the protein binding reagent (see e.g. paragraph [0006], claims 1-8). The unique identifier can be a nucleotide sequence (see e.g. paragraph [0006]). The sample for detection can be a single cell (see e.g. paragraph [0006], claim 14-15, 40). The nucleotide sequence can have a barcode, or molecular label sequence (see e.g. paragraph [0006]), which can also be combined with a poly A sequence, which can be used as a universal sequence (see e.g. paragraph [0006, claim 16]).
The protein binding reagent can also comprise an oligonucleotide sequence that can also
be a molecular barcode (see e.g. paragraph [0277]).
The method can comprise providing a sample of a plurality of protein targets, providing a
plurality of compositions comprising a protein binding reagent conjugated with an
oligonucleotide, wherein the oligonucleotide comprises a unique identifier, and contacting the
composition with the sample for binding of the protein target, removing the unbound binding
reagent, providing oligonucleotide probes, which comprises a target binding region and a
barcode sequence, contacting the probes with the binding reagent oligonucleotides, extending the
oligonucleotides that are hybridized with the probes, to create labeled nucleic acid sequences
with a unique identifier and barcode sequence, and determining the number of unique barcode
sequences for each unique identifier, to quantify the protein target in the sample (see e.g.
paragraph [0007], claims 28-43). The barcodes can comprise one or more universal labels (see
e.g. paragraph [0309]). The barcodes can provide information about the targets and samples (see
e.g. paragraph [0310], claim 20-23). The plurality of oligonucleotides can bc immobilized on
solid supports (see e.g. paragraph [0007]).
The solid support can be a bead (see e.g. paragraph [0312], [0339]), claim 48-49). The
barcode can be sequenced (see e.g. paragraph [0007]). The method can comprise detection of
both protein and nucleic acid targets from the same sample (see e.g. paragraph [0008]). There
can be at least 10,000 different unique identifiers (see e.g. claim 6).
The binding reagents can comprise antibodies, and can bind to proteins, etc. (see e.g.
paragraph [0008], claim 26). The antibody can be an IgG (see paragraphs [0023], [0037], [0280], [0331]; [0521], and claims 208, 287, and 383). The target can be on the surface of the cell, the proteins can be from cell lysing (see e.g. paragraph [0008], claim 41). There can be a first indexed target and a second indexed target, with the label regions being different (see e.g. paragraph [0435]). The size of the beads can vary, but the reference describes the same size range as the instant specification (see reference paragraph [0360] and instant specification paragraph [0152] from the published application). The dimensions can be similar to the dimensions of a cell (see e.g. paragraph [0361]).
The samples can be pooled and partitioned as needed to perform further processing (see
e.g. paragraph [0276], [0314], [0412] and [0745]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of
the invention to modify the method of Fan I with the barcoding technique of Fan II, which uses
the composition and/or kit of the '157 patent (Fan III), to count the number of molecules in a
method that corrects amplification bias, quantifies protein expression, allows more accurate
comparison of different samples by minimizing variation, provides means to simultaneously
measure protein and gene expression, and allows for the sample processing to take place using
less reagents and in a single reaction vessel (see e.g. '073 reference, paragraph [0005], [0274],
[0276], [0277], and [0411]). The claims do not clearly set forth the steps or the steps' order.
However, it would be expected, absent evidence to the contrary, one of skill in the art would be
able to identify the sequence of steps that would produce the most reproducible, noise-free signal
for the individual barcodes. The advantages of less reagents, multiplex detection of multiple
molecules simultaneously, greater accuracy, quantification of targets of interest, and reduction of
amplification bias provide the motivation to make the aforementioned modification of the method of Fan et al with the barcoding procedure of the '073 reference, with a reasonable expectation of success. 80. Additionally, KSR International Co. V. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person's skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Response to traversal
Applicant’s representative, at page 19 of the response of 18 November 2025, asserts:
Applicant respectfully disagrees with the double patenting rejections. Applicant respectfully requests the Examiner to hold the rejections in abeyance until the present application is otherwise in condition for allowance.
In view of the absence of convincing evidence as to how the claimed invention is not obvious over the cited application and patent documents, the rejections are maintained.
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682