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 .
Election/Restrictions
Applicant’s election, without traverse, of Group I (claims 1-5) in the reply filed on 9/11/2025 is acknowledged.
Claims 6-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 1/26/2023, is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner.
Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section”.
Claim Rejections - 35 USC § 112(a), lack of written description
4. 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.
4a. Claims 1-5 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.
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. 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 “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
Independent claim 1 is drawn to “a method of treating a subject afflicted with a chronic obstructive pulmonary disease comprising administering to the subject an epidermal growth factor (EGF)-depleting immunotherapeutic agent.”
Dependent claim 3 further limits claim 1 to “wherein the vaccine composition comprises as an active principle the conjugate between the recombinant human EGF and a carrier protein”.
The claims require administration of “an EGF-depleting immunotherapeutic agent”. The claims, however, do not require that the “EGF-depleting immunotherapeutic agent” recited in claim 1 possess any particular conserved structure, or other distinguishing feature. Furthermore, claim 2 recites “wherein the immunotherapeutic agent is a vaccine composition that induces the production of specific antibodies against the EGF” which limitations are only described by function and not by structure.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, and any combination thereof. In this case, the only factor present in the claims that is sufficiently disclosed is a recitation of a desired activity, “EGF-depleting immunotherapeutic agent”. The specification does not identify any particular portion of the structure, nor does it provide a disclosure of structure/function correlation. The distinguishing characteristics of the claimed genus for the “EGF-depleting immunotherapeutic agent” are not described. Accordingly, the specification does not provide adequate written description of the claimed genus of “EGF-depleting immunotherapeutic agents” to be administered in the claimed method.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (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”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the 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.
See University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 (DC WNY 2003) and University of Rochester v. G.D. Searle & Co. et al. CAFC [(03-1304) 13 February 2004]. In University of Rochester v. G.D. Searle & Co. a patent directed to method for inhibiting prostaglandin synthesis in human host using an unspecified compound, in order to relieve pain without side effect of stomach irritation, did not satisfy written description requirement of 35 U.S.C. §112, since the patent described the compound's desired function of reducing activity of the enzyme PGHS-2 without adversely affecting PGHS-1 enzyme activity, but did not identify said compound, since invention consists of performing “assays” to screen compounds in order to discover those with desired effect. The patent did not name even one compound that assays would identify as suitable for practice of the invention, or provide information such that one skilled in art could identify a suitable compound. And since the specification did not indicate that the compounds are available in a public depository, the claimed treatment method cannot be practiced without compound. Thus the inventors cannot be said to have “possessed” the claimed invention without knowing of a compound or a method certain to produce compound. Thus, said patent constituted an invitation to experiment to first identify, then characterize, and then use a therapeutic a class of compound defined only by their desired properties.
Therefore the full breadth of the claims fails to meet the written description provision of 35 U.S.C. §112(a). In the instant case, for example, Applicants have failed to describe which “EGF-depleting immunotherapeutic agent” has the desirable property of treating COPD in a subject in need thereof. 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.
To demonstrate possession of a method of treatment one must provide substantially more than the description of a compound or collection of related compounds having an in vitro activity, in combination with a hypothesis that the administration of a compound having that activity to an individual suffering from a particular disease or disorder might produce a beneficial effect. What is required is an established nexus between the administration of such a compound to an individual and a beneficial result consequent thereto. Such a nexus can be established by the presentation of evidence demonstrating clinical efficacy of the claimed method in the treatment of a particular disease or disorder, demonstrating efficacy of that method in the treatment of an art accepted animal model of a disease or disorder wherein that model is known to be reasonably predictive of the efficacy of a treatment protocol in the treatment of that disease or disorder, or providing evidence of an in vitro activity for the recited compound in combination with a showing that other compounds possessing that activity (mode of action) have been shown to have clinical efficacy in the treatment of the recited disease or disorder. The instant specification fails to show possession of the claimed method as of the effective filing date of the instant application because it only provides treatment with the therapeutic vaccine CIMAvax-EGF which induces anti-EGF antibodies (See page 5, Examples 1-2 and Table 1; page 6, Example 3).
As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
Whereas a reduction to practice of an uncomplicated invention such as a simple mechanical or electrical device can be achieved by merely providing a diagram of the device wherein one skilled in the relevant art can predict the likely operability of the device by reviewing the diagram, the operability of the claimed invention cannot be predicted by merely reviewing diagrams or illustrations. To demonstrate the reduction to practice of a method of treating a subject afflicted with a particular disease or disorder such as in the instant application, either a working embodiment, a demonstration of operability in the treatment of an art accepted animal model of the condition to be treated, wherein that animal model has been shown to be reliably predictive of efficacy in the treatment of the condition, or a demonstration that the therapeutic agent employed therein possesses an activity in which the majority of compounds possessing that activity have been shown to be effective in the treatment of that condition in the absence of further inventive contribution. In the instant case, Applicant has only provided the therapeutic vaccine CIMAvax-EGF which induces anti-EGF antibodies. Consequently, Applicant has failed to demonstrate possession of the claimed method of treatment by administering all “EGF-depleting immunotherapeutic agents” as of the earliest effective filing date of the instant application.
With respect to the demonstration of a reduction to practice of a generic invention, MPEP 2163(II)(A)(3)(ii) states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus, above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
In the instant case, at the time of filing, Applicant has failed to demonstrate possession of the claimed invention, i.e., a method of treating COPD by administering to the subject all “EGF-depleting immunotherapeutic agents” as recited in claim 1.
Claim Rejections - 35 U.S.C. § 112(b)
5. 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.
5a. Claims 1-5 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 pre-AIA the applicant regards as the invention.
Claim 1 is vague and indefinite for several reasons.
Claim 1 is vague and indefinite because it is a method claim but fails to recite steps in the method.
Claim 1 is vague and indefinite because it is a method claim but fails to recite “administering to the subject an effective amount….”.
Furthermore, claim 1 is vague and indefinite because the metes and bounds of the term “EGF-depleting immunotherapeutic agent” are unclear. It is suggested that the claim be amended to recite the specific “EGF-depleting immunotherapeutic agent” for which there is a basis in the instant specification (See pages 5-6, Examples 1-3).
Claim 2 is vague and indefinite because it fails to recite what “the vaccine composition” is. Therefore, the metes and bounds of the claim are unclear. It is suggested that the claim be amended to recite the specific “vaccine composition” for which there is a basis in the instant specification (See page 5, Example 2; page 6, Example 3).
Claim 3 recites the limitation "the conjugate" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 recites the limitation "the recombinant human EGF" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 4-5 are rejected as vague and indefinite insofar as they depend on the above rejected claims for their limitations.
Claim rejections-35 U.S.C. 103
6. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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, 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).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
6a. Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al (2006) in view of Rahman et al (2019) and Soemarwoto et al (2019).
The claims of the instant invention are directed to a method of treating a subject afflicted with a chronic obstructive pulmonary disease comprising administering to the subject an epidermal growth factor (EGF)-depleting immunotherapeutic agent, wherein the EGF-depleting immunotherapeutic agent is a vaccine composition comprising recombinant EGF and a carrier protein.
Malhotra et al (2006) discloses emerging drugs for the treatment of COPD (chronic obstructive pulmonary disease), and that airway mucus hypersecretion is a common feature of COPD and that EGFR is implicated in this process (See Section 4.3 on page 278, right column). The involvement of EGFR activation in the generation of abundant mucus in the airways of COPD patients is also disclosed (See Section 4.4, page 279, left column). On page 285, Table 6, one of the novel mucolytic medications to be used for COPD is disclosed to be Gefitinib, an EGFR inhibitor. On page 286, left column, last paragraph (Section 5.15.3), the reference discloses that Gefitinib, an inhibitor of EGFR, may be able to modify the deleterious effects of mucus hypersecretion in cancer patients and states that whether this can be effectively extrapolated to COPD patients remains to be seen. In view of the possible severe adverse events of Gefitinib the reference suggested that newer generations of EGFR blockers or tyrosine kinase modifiers may have fewer side effects with increased efficacy in modulating mucus secretion in COPD. The reference is silent with respect to a method of administering an EGF-depleting immunotherapeutic agent to treat COPD.
Rahman et al (2019) discloses that neutrophilic inflammation is central in COPD (See page 1, last paragraph). The reference further discloses that drugs that inhibit ErbB kinases (which are structurally related to EGFR) help to reduce inflammation by promoting death of neutrophils and since these drugs are used to treat cancer, the reference discloses that it may be possible to repurpose these drugs to treat COPD (See page 2, 5th paragraph).
Soemarwoto et al (2019) discloses that chronic mucus hypersecretion is a common feature in COPD and is associated with EGF activity (See abstract, first line of the background section). The reference concludes that the plasma levels of EGF may contribute to the pathogenesis of COPD (See last line of the abstract). The reference further discloses that highly elevated circulating levels of EGF are found in serum samples of COPD patients (See section bridging pages 24 and 25).
Therefore, it would have been obvious to one of ordinary skill in the art, at the time the instant invention was conceived, to modify the method of Samir et al and administer an agent that inhibits EGF (which EGF stimulates EGFR), to treat COPD in view of the combined teachings of Rahman et al and Soemarwoto et al, which establishes a link between higher expression of EGF in COPD and provides the motivation to a person skilled in the art to inhibit EGFR signaling by depleting EGF with an EGF-depleting immunotherapeutic agent, such as a vaccine composition that induces the production of EGF specific antibodies, with an expectation of success.
Therefore, the combination of references renders obvious claims 1-2 in the absence of evidence to the contrary.
6b. Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al (2006) in view of Rahman et al (2019) and Soemarwoto et al (2019) and further in view of US 2019/0008939 A1 (‘939).
The teachings of Malhotra et al (2006), Rahman et al (2019) and Soemarwoto et al (2019), are set forth above in paragraph 6a. The references are silent with respect to a method of administering a vaccine composition comprising EGF conjugated to a carrier protein.
‘939 teaches that that when the antigen of interest is of low molecular weight, or is poorly immunogenic, coupling to an immunogenic carrier is recommended, examples of such carrier molecules include keyhole limpet haemocyanin (KLH), bovine serum albumin, ovalbumin and fowl immunoglobulin (See [0323]). The reference also discloses that a carrier may be present independently of an adjuvant to increase the molecular weight of peptide fragments in order to increase their activity or immunogenicity, to confer stability, to increase the biological activity, or to increase serum half-life (See [0324]).
It would have been obvious to one of ordinary skill in the art, at the time the instant invention was conceived, to modify the method as disclosed by Malhotra et al (2006) in view of Rahman et al (2019) and Soemarwoto et al (2019) and conjugate the low molecular weight EGF protein (53 amino acids) to a carrier protein, such as KLH, to increase the molecular weight of the EGF protein and to increase its immunogenicity as disclosed by ‘939 which provides the motivation and expectation of success to conjugate EGF with KLH.
Therefore, the combination of references renders obvious claims 1-4 in the absence of evidence to the contrary.
6c. Claims 1-2, 5 are rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al (2006) in view of Rahman et al (2019) and Soemarwoto et al (2019) and further in view of US 2019/0367561 A1 (‘561).
The teachings of Malhotra et al (2006), Rahman et al (2019) and Soemarwoto et al (2019), are set forth above in paragraph 6a. The references are silent with respect to a method of administering an EGF vaccine composition comprising an adjuvant.
‘561 discloses that adjuvants such as incomplete Freund’s adjuvant, oil adjuvants (emulsifiers) such as liquid paraffin (mineral origin), cod liver oil (animal origin), and olive oil (plant origin), are convenient, readily available and commonly used to enhance the protective efficacy and enhance the immune response to a vaccine by creating a water-in-oil emulsion to act as a "depot" that slowly releases the antigen at the injection site, boosting the immune response due to the slow release which creates a sustained exposure to the antigen and promotes a longer-lasting and higher antibody response compared to an antigen alone (See [257-258]).
It would have been obvious to one of ordinary skill in the art, at the time the instant invention was conceived, to modify the method as disclosed by Malhotra et al (2006) in view of Rahman et al (2019) and Soemarwoto et al (2019) and add an adjuvant like incomplete Freund’s adjuvant to the vaccine composition to enhance the protective efficacy of the vaccine as disclosed by ‘561 which provides the motivation and expectation of success to add adjuvants to vaccine compositions.
Therefore, the combination of references renders obvious claims 1-2, and 5 in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Claims 1-5 are rejected.
Advisory Information
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/PREMA M MERTZ/ Primary Examiner, Art Unit 1674