DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
2. Applicant is advised that the Final Rejection mailed 05/15/25 is vacated. Prosecution is reopened herein. The rejection of claims 19-30 under 35 U.S.C. 101 as claiming the same invention as that of claims 1-12 of U.S. Patent No. 11,389,518, found on page 3 at paragraph 6, is withdrawn.
Claim Status
3. Claims 19-30 are pending and under examination. Claims 1-18 are cancelled.
New Objection: Claim Objections
4. Claim 26 is objected to because of the following informalities: typos. Claim 26 improperly recites “form” (see line 2) wherein “from” is proper. In addition, claim 26 is objected to for recitation of “a lung lesions” which should be either singular or plural, but not both. Appropriate correction is required.
5. Claim 29 is objected to because of the following informalities: typos. Claim 29 improperly recites “form” (see line 2) wherein “from” is proper. In addition, claim 29 is objected to for recitation of “a lung lesions” which should be either singular or plural, but not both. Appropriate correction is required.
New Rejection: Claim Rejections - 35 USC § 112
6. 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.
7. Claims 19-29 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 19 is indefinite because it is drawn to “A Mycoplasma bovis strain, wherein said strain is deposited…” which necessarily must be in a composition but is not claimed as such. Therefore, it is unclear how the strain per se is deposited without being in a composition and clarification is required.
Further the term “progeny” in claim 19 is open-ended and thus indefinite because it is unclear how many generations and/or how much variation (e.g. mutations/genetic drift) would be included vs. excluded from the metes and bounds of the claim? The specification states “The term “parent” or “parental strain”, as used herein, means the entity from which offspring, or progeny, are derived. The term “progeny”, as used herein, means that produced by, or derived from, one or more parents or parental strains” (see page 9, lines 26-28). Thus, the circularity of the definitions does not provide guidance regarding the number of generations and/or the amount of variation encompassed by the progeny option. In addition, the specification states: “Another embodiment provides a method of mutagenizing a parental strain of M. bovis, wherein the progeny strain is deposited with the American Type Culture and Collection under accession number PTA-122167.” (see page 4, lines 14-16). Thus, it is unclear what M. bovis PTA-122167 encompasses (e.g. parent or progeny?) and thus clarification is required ascertain the metes and bounds of the claim.
The term “modified” in claim 20 is a relative term which renders the claim indefinite. The term “modified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of modification of the live strain is included vs. excluded in the limitation? Thus, clarification is required to remove scope ambiguity.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired; See MPEP § 2173.05(c). In the present instance, claim 24, claim 25, and claim 27 recite the broad recitation “the animal”, and the claim also recites “a bovine animal” which is the narrower statement of the limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 25 recites the limitation "…the immunogenic composition of claim 19" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim, because claim 19, as written, is not drawn to a composition (see above).
The terms “lameness” and “difficulty” in claim 26 and claim 29 are each a relative term which renders the claim indefinite. The terms “lameness” and “difficulty” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of lameness and/or to what degree of difficulty breathing is included vs. excluded in the limitation(s) of claim 26? Thus, clarification is required to remove scope ambiguity.
Claim 28 recites the limitation "…said additional infectious agent…" in line 2. There is insufficient antecedent basis for this limitation in the claim, there is no recitation of an additional infectious agent in claim 22, from which it depends.
Other dependent claims do not clarify the issues identified above. Therefore, clarification is required to remove ambiguity of scope and thereby clearly ascertain the metes and bounds of the claims.
New Rejection: Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claim 20 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 20 is improperly drawn to an immunogenic composition comprising the strain of claim 19, wherein the strain is a modified live strain. Thus, claim 20 is substantially broader than claim 19 (i.e. fails to further limit) by allowing modifications to the strain in claim 19, from which it directly depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New Rejection: Claim Rejections - 35 USC § 112
10. 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.
11. Claims 19-30 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention.
Instant claims are drawn to immunogenic compositions comprising a Mycoplasma bovis strain, wherein said strain is deposited with the American Type Culture Collection under accession number PTA-122167, or wherein said strain is a progeny of M bovis strain PTA-122167 wherein said progeny of M bovis strain PTA-122167 is obtained by passaging strain PTA-122167; … wherein said strain is a modified live strain; and further to methods of preventing diseases caused by Mycoplasma bovis and other infectious agents including those of all viruses, bacteria, parasites and/or fungi and/or preventing clinical signs of diseases both in general and specifically lung lesions, pyrexia, cough, lameness, and/or difficulty breathing. Consequently, it is the Office’s position that (1) the independent claim(s) constitute(s) a "broad generic claim” based on the phrases “…or a progeny…” and/or “…a modified live strain…” and (2) the claimed genus has substantial variation because of the numerous options permitted.
MPEP §2163 states that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species (i.e. examples) that encompass the genus. If the genus has a substantial variance (as in the instant case), the disclosure must describe a sufficient variety of species (i.e. examples) to reflect the variation within that genus. 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 to adequately describe a broad genus. The courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus (e.g. see In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618). Further, MPEP §2163 states that the disclosure of only one or two 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) "[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).
With regards to the Mycoplasma bovis strain deposited with ATCC under accession number PTA-122167 (see claims 19 and 30); it is noted that the instant specification describes this strain to be both the actual strain deposited (i.e. see page 2, lines 7-9; and page 11, lines 11-15) reproduced here: “In certain embodiments of the present invention, a Mycoplasma bovis strain from a bovine has been attenuated, as well as characterized. An isolate of said M. bovis strain was deposited with the American Type Culture Collection ("ATCC"), Manassas, VA, USA, on May 12, 2015, and has been assigned accession number, PTA-122167” (i.e. page 11, emphasis added) and a progeny thereof (i.e. see page 4, lines 14-16) reproduced here: “Another embodiment provides a method of mutagenizing a parental strain of M. bovis, wherein the progeny strain is deposited with the American Type Culture and Collection under accession number PTA-122167.” (emphasis added, see page 4, lines 14-16). Thus, the specification does not adequately describe what Mycoplasma bovis with an ATCC accession number of PTA-122167 encompasses (e.g. parent or progeny?).
With regards to “progeny” (see claim 19), the specification does not provide adequate written description support for the starting material deposited as PTA-122167 with ATCC (see above); but even if it did, the specification does not adequately describe progeny thereof. In fact, one cannot have possession of the future before it arrives. MPEP 2163 also states an adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed; emphasis added; see, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004); See also Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"); see also MPEP 2163.
With regards to “modified live strains” (see claim 20) in general, and/or specifically of Mycoplasma bovis PTA-122167; the specification describes that “modified live (attenuated) vaccines” are a preferred aspect of their invention (see page 25, lines 7-10; and Example 2). However, based on the conflicting statements within the disclosure, the specification does not provide adequate written description support for the starting material (see above); but even if it did, the specification does not provide adequate written description for unlimited modifications of this particular strain, or of Mycoplasma bovis in general, to predictably produce immunogenic compositions for preventing diseases and/or clinical signs of diseases caused by Mycoplasma bovis. The specification describes M. bovis N2805-01 has having 12 single nucleotide differences relative to an 3683 M. bovis strain; however, the specification does not adequately describe the relationship between M. bovis PTA-122167 and that of either M. bovis N2805-01 and/or 3683 M. bovis; (see Example 1).
With regards to methods of prevention (i.e. of disease or clinical signs of disease; see claims 24, 27, 28, and 29), the specification describes a study comparing results a control group (T01, saline) to 3 vaccine treatment groups, including T02 (M. bovis N2805-1); T03 (a reference experimental M. bovis vaccine); and T04 (temperature-sensitive M. bovis N2805-1) subsequently challenged with M. bovis Kansas strain 110-LA-11-10 (see Example 2) in which significant reductions in percent lung lesions (Table 4); mean duration of pyrexia (Table 5); cough, lameness and respiratory efforts (Table 7) were recorded for each of the vaccine treatment groups (i.e. T02, T03, and T04). However, the specification does not adequately describe the relationship between M. bovis PTA-122167 and the M. bovis administered to the three vaccine treatment groups. The specification does not adequately describe any methods of prevention of disease or of clinical signs of disease as evidenced by the non-zero (albeit lower) results obtained even in the vaccine treatment groups (i.e. reductions and protections are not equivalent to prevention). The specification does not adequately describe administration of compositions comprising additional antigens and/or methods for preventing diseases caused by other infectious agents. Consequently, the specification does not adequately describe any methods for preventing a disease caused by Mycoplasma bovis and/or another infectious agent in a bovine animal comprising administering Mycoplasma bovis PTA-122167 alone, or in a composition with additional antigens, with or without carriers, excipients and/or adjuvants.
With regards to methods for reducing clinical signs of disease caused by Mycoplasma bovis (see claims 25 and 26), similar to the previous paragraph, the specification does not adequately describe the relationship between M. bovis PTA-122167 and the M. bovis administered to the three vaccine treatment groups for which the results are summarized. Further, the specification describes reducing the percentage of lung lesions (Table 4); mean duration of pyrexia (Table 5); cough, lameness and respiratory efforts (Table 7); but does not adequately describe reducing any and all clinical signs of diseases (except those noted) either caused by M. bovis and/or all other infectious agents (e.g. any and all diseases caused by viruses, other bacteria, parasites and/or fungi). The specification does not adequately describe a nexus between the limited results obtained and reducing any other clinical signs of diseases either caused by M. bovis and/or all other infectious agents as broadly as is claimed. In contrast, the specification describes at least one clinical sign (i.e. droopy ear/head tilt) was not only not reduced, but rather it was actually increased relative to the control group (see Table 7). Thus, the specification provides evidence that there is unpredictability in the results obtained from species (i.e. examples) other than those specifically enumerated, and accordingly, provides evidence which indicates even skilled artisans could not reliably predict the operability in the invention of any species other than the one disclosed.
With regards to the methods of making a vaccine (see claim 30), the specification describes “serial passage” as a method for purifying an organism, preferably a microorganism, to obtain a clonally pure population, but does not adequately describe the particulars of passaging for making vaccines, either in general or in particular for Mycoplasma bovis. The specification describes generation and isolation of a Mycoplasma bovis mutant (see Example 1), but does not adequately link the process steps in Example 1 specifically, to making vaccines in general. The specification does not adequately describe what was in the tested compositions other than the M. bovis variant (or saline) and therefore does not adequately describe vaccines with or without carriers, excipients and/or adjuvants. Accordingly, it is the Office’s position that one of skill in the art would not accept the instant disclosure as having a sufficient number and/or variety of “representative species” for all of the options and combinations of options encompassed by the broad and variable generic claims regarding M. bovis PTA-122167 and/or the unlimited progeny and modified live versions thereof. Consequently, the specification also does not adequately describe methods of prevention of diseases or clinical signs via the use of the strain and/or its progeny and/or the poorly described modifications. Therefore, it is the Office’s position that one of skill in the art would not conclude that Applicant was in possession of the genus.
With regards to the state of the art, determining genetic profiles of Mycoplasma bovis strains subjected to passaging (i.e. the progeny of parental strains) could not be predicted from the parental strain genotype, as evidenced by, for example, Rasheed et al. 2017 (Comparative Genomics of Mycoplasma bovis Strains Reveals that Decreased Virulence with Increasing Passages Might Correlate with Potential Virulence-Related Factors; Frontiers in Cellular and Infection Microbiology vol 7, article 177). Rasheed demonstrated there are measurable differences in the genotypes of three attenuated strains of M. bovis compared to each other and to the parental strain (see abstract; materials and methods, first paragraph; and Table 2). Therefore, Rasheed supports that even a skilled artisan would require guidance on the genetic profile of the progeny produced via serial passaging and/or the details of the methods for the serial passaging per se. Accordingly, the state of the art (i.e. article published 2 years after the application was filed) provides evidence that there is unpredictability in the results obtained from species (i.e. examples) other than those specifically enumerated (i.e. in the instant case, zero bearing a sufficient resemblance to what is claimed), and consequently, evidence that indicates skilled artisans could not reliably predict the operability in the invention of any species other than what is disclosed.
Consequently, neither the specification nor the state of the art provides sufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "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.). Given the above analysis of the factors as a whole, which the courts have determined are critical in determining whether Applicant is in possession of or the specification supports the claimed invention, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
New Rejection: Claim Rejections - 35 USC § 112
12. Claims 19-30 are rejected under 35 U.S.C. 112(a) 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.
Factors to be considered in determining whether undue experimentation is required, are set forth in In re Wands, 8 USPQ2d 1400. 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 those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims. Although all the factors were considered, the most relevant ones are discussed below. In the instant case:
Nature of the invention: The nature of the invention is immunogenic compositions comprising a Mycoplasma bovis strain, wherein said strain is deposited with the American Type Culture Collection under accession number PTA-122167, or wherein said strain is a progeny of M bovis strain PTA-122167, wherein said progeny of M bovis strain PTA-122167 is obtained by passaging strain PTA-122167; wherein said strain is a modified live strain; and further to methods of preventing diseases caused by Mycoplasma bovis and other infectious agents including those of all viruses, bacteria, parasites and/or fungi and/or preventing clinical signs of diseases both in general and specifically lung lesions, pyrexia, cough, lameness, and/or difficulty breathing. Therefore, the nature of the invention is a chemical case, where there is natural unpredictability in performance of certain species or sub-combinations other than those specifically enumerated; see MPEP 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the claimed methods, with a reasonable expectation of success, because it would not be predictable from the disclosure of one particular species (e.g. no examples bearing a sufficient resemblance to the claims) what other species (e.g. progeny; unlimited modifications; any/all diseases and clinical signs of diseases) may or may not work; see MPEP 2164.03. Therefore, the claims are not enabled because even the skilled artisan cannot make and use the invention, with a reasonable expectation of success, without an undue amount of experimentation first.
Breadth of the claims: The broadest reasonable interpretation of the claims covers numerous, distinct, immunogenic compositions based on the claimed options encompassing “progeny” (see claim 19) and/or the unlimited modifications (see claim 20) of a Mycoplasma bovis strain as products and/or as used for preventing numerous, distinct, diseases and/or the clinical signs of diseases caused by Mycoplasma bovis along with those caused by any and all viruses, other bacteria, parasites and/or fungi, in a diverse group of medium- to large- sized ungulates, including, but not limited to, domestic cattle, bison, African buffalo, water buffalo, yak, four-horned and spiral-horned antelope, using any and all routes of administration including intramuscular, subcutaneous, intranasal, intratracheal, oral and aerosol haphazardly mixed-and-matched with poorly described antigens from Haemophilus somnus, Haemophilus parasuis, Bordetella bronchiseptica, Bacillus anthracis, Actinobacillus pleuropneumonie, Pasteurella multocida, Mannhemia haemolytica, Mycobacterium bovis, Mycobacterium paratuberculosis, Clostridial spp., Streptococcus uberis, Staphylococcus aureus, Erysipelothrix rhusopathiae, Chlamydia spp., Brucella spp., Vibrio spp., Salmonella enterica serovars, Leptospira spp, Candida, Cryptosporidium parvum, Neospora canium, Toxoplasma gondii, Eimeria spp., Babesia spp., Giardia spp., Ostertagia, Cooperia, Haemonchus, Fasciola, bovine coronavirus, bovine rotavirus, bovine herpesviruses, bovine parainfluenza virus, bovine viral diarrhea virus, bovine adenovirus, bovine rhinovirus, bovine reovirus, bovine respiratory syncytial virus, bovine leukosis virus, rinderpest virus, foot and mouth disease virus, and rabies virus.
However, without guidance on which of the structural components are required (i.e. which progeny, which modifications, which antigens, which diseases, which clinical signs, which animals, which routes of administration, etc.) to maintain their claimed functions (i.e. prevention of diseases and clinical signs of disease) undue experimentation would be require to determine which of the combinations actually work. Accordingly, undue experimentation would be required to practice the claimed invention, with a reasonable expectation of success, because while enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed and such guidance has not been provided in the instant specification. Therefore, the claims are not enabled because even the skilled artisan cannot make and use the invention, with a reasonable expectation of success, without an undue amount of experimentation first.
Amount of direction provided by Inventor and Existence of Working Examples: With regards to the Mycoplasma bovis strain deposited with ATCC under accession number PTA-122167 (see claims 19 and 30); it is noted that the instant specification states this strain to be both the actual strain deposited (i.e. see page 2, lines 7-9; and page 11, lines 11-15) reproduced here: “In certain embodiments of the present invention, a Mycoplasma bovis strain from a bovine has been attenuated, as well as characterized. An isolate of said M. bovis strain was deposited with the American Type Culture Collection ("ATCC"), Manassas, VA, USA, on May 12, 2015, and has been assigned accession number, PTA-122167” (i.e. page 11, emphasis added) and a progeny thereof (i.e. see page 4, lines 14-16) reproduced here: “Another embodiment provides a method of mutagenizing a parental strain of M. bovis, wherein the progeny strain is deposited with the American Type Culture and Collection under accession number PTA-122167.” (emphasis added, see page 4, lines 14-16). Thus, the specification does not sufficiently provide for what Mycoplasma bovis with an ATCC accession number of PTA-122167 actually encompasses (e.g. parent or progeny?).
With regards to “progeny” (see claim 19), the specification does not sufficiently provide for the starting material deposited as PTA-122167 with ATCC (see above); but even if it did, the specification does not sufficiently provide for the progeny thereof.
With regards to “modified live strains” (see claim 20) in general, and/or specifically of Mycoplasma bovis PTA-122167; the specification states that “modified live (attenuated) vaccines” are a preferred aspect of their invention (see page 25, lines 7-10; and Example 2). However, based on the conflicting statements within the disclosure, the specification does not provide support for the starting material (see above); but even if it did, the specification does not sufficiently provide for unlimited modifications of this particular strain, or of Mycoplasma bovis in general, to predictably produce immunogenic compositions for preventing diseases and/or clinical signs of diseases caused by Mycoplasma bovis. The specification states M. bovis N2805-01 has 12 single nucleotide differences relative to an 3683 M. bovis strain; however, the sufficiently disclose the relationship between M. bovis PTA-122167 and that of either M. bovis N2805-01 and/or 3683 M. bovis; (see Example 1).
With regards to methods of prevention (i.e. of disease or clinical signs of disease; see claims 24, 27, 28, and 29), the specification provides a study comparing results a control group (T01, saline) to 3 vaccine treatment groups, including T02 (M. bovis N2805-1); T03 (a reference experimental M. bovis vaccine); and T04 (temperature-sensitive M. bovis N2805-1) subsequently challenged with M. bovis Kansas strain 110-LA-11-10 (see Example 2) in which significant reductions in the percentage of lung lesions (Table 4); mean duration of pyrexia (Table 5); and cough, lameness and respiratory efforts (Table 7) were recorded for each of the vaccine treatment groups (i.e. T02, T03, and T04). However, the specification does not sufficiently disclose the relationship between M. bovis PTA-122167 and the M. bovis administered to the three vaccine treatment groups. The specification does not sufficiently disclose any methods of prevention of disease or of clinical signs of disease as evidenced by the non-zero (albeit lower) results obtained even in the vaccine treatment groups (i.e. reductions and protections are not equivalent to prevention). The specification does not sufficiently disclose administration of compositions comprising additional antigens and/or methods for preventing diseases caused by other infectious agents. Consequently, the specification does not sufficiently disclose any methods for preventing a disease caused by Mycoplasma bovis and/or another infectious agent in a bovine animal comprising administering Mycoplasma bovis PTA-122167 alone, or in a composition with additional antigens, with or without carriers, excipients and/or adjuvants.
With regards to methods for reducing clinical signs of disease caused by Mycoplasma bovis (see claims 25 and 26), similar to the previous paragraph, the specification does not sufficiently disclose the relationship between M. bovis PTA-122167 and the M. bovis administered to the three vaccine treatment groups for which the results are summarized. Further, the specification states that reducing the percentage of lung lesions (Table 4); mean duration of pyrexia (Table 5); and cough, lameness and respiratory efforts (Table 7); but does not sufficiently disclose reducing any and all clinical signs of diseases (except those noted) either caused by M. bovis and/or all other infectious agents (e.g. any and all diseases caused by viruses, other bacteria, parasites and/or fungi). The specification does not sufficiently disclose a nexus between the limited results obtained and reducing any other clinical signs of diseases either caused by M. bovis and/or all other infectious agents. In contrast, the specification reports that at least one clinical sign (i.e. droopy ear/head tilt) was not only not reduced, but rather it was actually increased relative to the control group (see Table 7). Thus, the specification provides evidence that there is unpredictability in the results obtained from species (i.e. examples) other than those specifically enumerated, and accordingly, provides evidence which indicates even skilled artisans could not reliably predict the operability in the invention of any species other than the one disclosed.
With regards to the methods of making a vaccine (see claim 30), the specification designates “serial passage” as a method for purifying an organism, preferably a microorganism, to obtain a clonally pure population, but does not sufficiently disclose the particulars of passaging for making vaccines, either in general or in particular for Mycoplasma bovis. The specification reports generation and isolation of a Mycoplasma bovis mutant (see Example 1), but does not adequately link the process steps in Example 1 specifically, to making vaccines in general. The specification does not sufficiently disclose what was in the tested compositions other than the M. bovis variant (or saline) and therefore does not sufficiently disclose vaccines with carriers, excipients and/or adjuvants.
Accordingly, the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification and the only way to determine if a particular combination is works, is empirical testing by starting from scratch to determine which progeny, which modifications, with which carriers, excipients, and/or adjuvant, with which additional antigens, in which doses and schedules, would reliably prevent which diseases and/or reduce which clinical signs of disease in which animals. With specific regards to claim 30, it is noted that the skilled artisan must first determine culturing and passaging details before the methods can be practiced and then must determine what else is needed in the vaccine composition.
Consequently, based on the almost unfathomable number of possible combinations, a non-routine amount of experimentation would be required to practice the invention, with a reasonable expectation of success, and testing such a vast number of combinations would be easily recognized by the skilled practitioner to be disproportionately demanding and thus rise to the level of non-routine. Therefore, the claims are not enabled because even the skilled artisan cannot make and use the invention, with a reasonable expectation of success, without an undue amount of experimentation first.
State of the Prior Art and Level of Predictability in the Art: At the time of filing, the state of the art was such that the genetic profiles of Mycoplasma bovis strains subjected to passaging (i.e. the progeny of parental strains) could not be predicted from the parental strain genotype, as evidenced by, for example, Rasheed et al. 2017 (Comparative Genomics of Mycoplasma bovis Strains Reveals that Decreased Virulence with Increasing Passages Might Correlate with Potential Virulence-Related Factors; Frontiers in Cellular and Infection Microbiology vol 7, article 177). Rasheed demonstrated there are measurable differences in the genotypes of three attenuated strains of M. bovis compared to each other and to its parental strain (see abstract; materials and methods, first paragraph; and Table 2). Therefore, Rasheed supports that even a skilled artisan would require guidance on the genetic profile of the progeny produced via serial passaging and/or the details of the methods for the serial passaging. Thus, the state of the art (i.e. the article was published 2 years after the application was filed) provides evidence that there is unpredictability in the results obtained from species (i.e. examples) other than those specifically enumerated (in the instant case, zero), and accordingly, evidence that indicates skilled artisans could not reliably predict the operability in the invention of any species other than what is disclosed.
Relative Skill of Those in the Art: The relative level of skill of those in the art is deemed to be high (e.g. PhD/MD level); however, even one of skill in the art could not predictably extrapolate the limited (and conflicting) teachings in the specification, limited to results obtained from a Mycoplasma bovis strain that is not claimed, to all of the other compositions and methods, encompassed, as broadly as is claimed. The skilled artisan simply cannot envision the combinations required, thus conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used to determine such options or to test for such properties based on the interpretation of the claims as currently written. Thus, even one of skill in the art, given its unpredictability, would have to engage in undue experimentation to determine which combinations of options retain the necessary results and thereby carry out the invention as claimed.
Quantity of Experimentation Necessary Based on Content of the Disclosure: The specification does not enable the genus because where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims; In re Soil, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required; In re Fisher, 427 F.2d 833,839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity); see also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); and In re Vaeck, 947 F.2d 488,496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). Accordingly, without such guidance, the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue; See Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F, 2d 1200, 18 USPQ 1016 (Fed. Cir. 1991) at 18 USPQ 1026 1027 and Exparte Forman, 230 USPQ 546 (BPAI 1986). It is noted that providing methods for determining which progeny and/or which modifications, and/or which other antigens, would not reduce the amount of experimentation required to determine which of numerous options would retain their ability to prevent which diseases and/or clinical signs because the desired results still must be determined empirically.
Therefore, in view of the lack of guidance and direction provided by Applicant there would be undue experimentation required to practice the claimed invention, with a reasonable expectation of success, absent a specific and detailed description in Applicant's specification of how to effectively make and/or use the claimed invention. Thus, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
New Rejection: Double Patenting
13. 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.
14. Claims 19-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,389,518. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to substantially the same bacterial strain, in substantially the same immunogenic compositions, and used for substantially the same purposes for substantially the same population. For example:
Instant claims are drawn to: A Mycoplasma bovis strain, wherein said strain is deposited with the American Type Culture Collection under accession number PTA-122167, or wherein said strain is a progeny of M bovis strain PTA-122167 wherein said progeny of M. bovis strain PTA-122167 is obtained by passaging strain PTA-122167; and to an immunogenic composition comprising the Mycoplasma bovis strain wherein said strain is a modified live strain; further comprising at least one additional antigen; wherein the additional antigen is selected from the group consisting of a virus, a bacterium, a fungus and a parasite; formulated for administration by a route selected from the group consisting of intramuscular, subcutaneous, intranasal, intratracheal, oral and aerosol; and a method for preventing disease caused by Mycoplasma bovis in a bovine animal, comprising administering to the animal the immunogenic composition; and a method for reducing at least one clinical sign of disease caused by Mycoplasma bovis in a bovine animal, comprising administering to the animal the immunogenic composition; wherein said at least one clinical sign is selected from the group consisting of lung lesions, pyrexia, cough, lameness, and difficulty breathing. For completeness, it is noted that the instant specification defines “immunogenic composition” to include “a composition that generates an effective immune response” (see page 8, lines 13-16) and defines effective immunogenic compositions as protecting (see page 12, line 27).
Likewise, patented claims are also drawn to an effective immunogenic composition comprising a Mycoplasma bovis strain, wherein said strain is deposited with the American Type Culture Collection under accession number PTA-122167, or wherein said strain is a progeny of M bovis strain PTA-122167 wherein said progeny of M bovis strain PTA-122167 is obtained by passaging strain PTA-122167; wherein said M. bovis strain is inactivated; wherein the composition additionally comprises an adjuvant; further comprising at least one additional antigen; wherein the additional antigen is selected from the group consisting of a virus, a bacterium, a fungus and a parasite; wherein said composition is formulated for administration by a route selected from the group consisting of intramuscular, subcutaneous, intranasal, intratracheal, oral and aerosol; and a method for preventing disease caused by Mycoplasma bovis in a bovine animal, comprising administering to the animal an immunizing amount of the immunogenic composition; and a method for preventing diseases caused by Mycoplasma bovis and another infectious agent of a bovine animal, comprising administering to the animal an immunizing amount of the immunogenic composition; and a method for reducing at least one clinical sign of disease caused by Mycoplasma bovis in a bovine animal, comprising administering to the animal an immunizing amount of the immunogenic composition; wherein said at least one clinical sign is selected from the group consisting of lung lesions, pyrexia, cough, lameness, and difficulty breathing; and a method for preventing at least one clinical sign of diseases caused by Mycoplasma bovis and another infectious agent of a bovine animal, comprising administering to the animal an immunizing amount of the immunogenic composition; wherein said at least one clinical sign of the disease caused by M. bovis is selected form the group consisting of lung lesions, pyrexia, cough, lameness, and difficulty breathing.
Therefore, the instant claims are drawn to the substantially the same invention as the patented claims and are thereby not patentably distinct.
Conclusion
15. No claims are allowed.
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/MARY MAILLE LYONS/Examiner, Art Unit 1645
September 30, 2025